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Sample records for action potential parameters

  1. Determination of cable parameters in skeletal muscle fibres during repetitive firing of action potentials

    Science.gov (United States)

    Riisager, Anders; Duehmke, Rudy; Nielsen, Ole Bækgaard; Huang, Christopher L; Pedersen, Thomas Holm

    2014-01-01

    Recent studies in rat muscle fibres show that repetitive firing of action potentials causes changes in fibre resting membrane conductance (Gm) that reflect regulation of ClC-1 Cl− and KATP K+ ion channels. Methodologically, these findings were obtained by inserting two microelectrodes at close proximity in the same fibres enabling measurements of fibre input resistance (Rin) in between action potential trains. Since the fibre length constant (λ) could not be determined, however, the calculation of Gm relied on the assumptions that the specific cytosolic resistivity (Ri) and muscle fibre volume remained constant during the repeated action potential firing. Here we present a three-microelectrode technique that enables determinations of multiple cable parameters in action potential-firing fibres including Rin and λ as well as waveform and conduction velocities of fully propagating action potentials. It is shown that in both rat and mouse extensor digitorum longus (EDL) fibres, action potential firing leads to substantial changes in both muscle fibre volume and Ri. The analysis also showed, however, that regardless of these changes, rat and mouse EDL fibres both exhibited initial decreases in Gm that were eventually followed by a ∼3-fold, fully reversible increase in Gm after the firing of 1450–1800 action potentials. Using this three-electrode method we further show that the latter rise in Gm was closely associated with excitation failures and loss of action potential signal above −20 mV. PMID:25128573

  2. Sensitivity of the amplitude of the single muscle fibre action potential to microscopic volume conduction parameters

    NARCIS (Netherlands)

    Alberts, B.A.; Rutten, Wim; Wallinga, W.; Boom, H.B.K.

    1988-01-01

    A microscopic model of volume conduction was applied to examine the sensitivity of the single muscle fibre action potential to variations in parameters of the source and of the volume conductor, such as conduction velocity, intracellular conductivity and intracellular volume fraction. The model

  3. A distribution analysis of action potential parameters obtained from patch-clamped human stem cell-derived cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Fernando López-Redondo

    2016-06-01

    Full Text Available We investigated electrophysiological properties of human induced-pluripotent-stem-cell-derived and embryonic-stem-cell-derived cardiomyocytes, and analyzed action potential parameters by plotting their frequency distributions. In the both cell lines, the distribution analysis revealed that histograms of maximum upstroke velocity showed two subpopulations with similar intersection values. Sub-populations with faster maximum upstroke velocity showed significant prolongation of action potential durations by application of E-4031, whereas others did not, which may be partly due to shallower maximum diastolic potentials. We described electrophysiological and pharmacological properties of stem-cell-derived cardiomyocytes in the respective sub-populations, which provides a way to characterize diverse electrical properties of stem-cell-derived cardiomyocytes systematically.

  4. The influence of noise exposure on the parameters of a convolution model of the compound action potential.

    Science.gov (United States)

    Chertoff, M E; Lichtenhan, J T; Tourtillott, B M; Esau, K S

    2008-10-01

    The influence of noise exposure on the parameters of a convolution model of the compound action potential (CAP) was examined. CAPs were recorded in normal-hearing gerbils and in gerbils exposed to a 117 dB SPL 8 kHz band of noise for various durations. The CAPs were fitted with an analytic CAP to obtain the parameters representing the number of nerve fibers (N), the probability density function [P(t)] from a population of nerve fibers, and the single-unit waveform [U(t)]. The results showed that the analytic CAP fitted the physiologic CAPs well with correlations of approximately 0.90. A subsequent analysis using hierarchical linear modeling quantified the change in the parameters as a function of both signal level and hearing threshold. The results showed that noise exposure caused some of the parameter-level functions to simply shift along the signal level axis in proportion to the amount of hearing loss, whereas others shifted along the signal level axis and steepened. Significant changes occurred in the U(t) parameters, but they were not related to hearing threshold. These results suggest that noise exposure alters the physiology underlying the CAP, some of which can be explained by a simple lack of gain, whereas others may not.

  5. Algorithm for multi-curve-fitting with shared parameters and a possible application in evoked compound action potential measurements.

    Science.gov (United States)

    Spitzer, Philipp; Zierhofer, Clemens; Hochmair, Erwin

    2006-02-22

    Experimental results are commonly fitted by determining parameter values of suitable mathematical expressions. In case a relation exists between different data sets, the accuracy of the parameters obtained can be increased by incorporating this relationship in the fitting process instead of fitting the recordings separately. An algorithm to fit multiple measured curves simultaneously was developed. The method accounts for parameters that are shared by some curves. It can be applied to either linear or nonlinear equations. Simulated noisy "measurement results" were created to compare the introduced method to the "straight forward" way of fitting the curves separately. The analysis of the simulated measurements confirm, that the introduced method yields more accurate parameters compared to the ones gained by fitting the measurements separately. Therefore it needs more computer time. As an example, the new fitting algorithm is applied to the measurements of the evoked compound action potentials (ECAP) of the auditory nerve: This leads to promising ideas to reduce artefacts generated by the measuring process. The introduced fitting algorithm uses the relationship between multiple measurement results to increase the accuracy of the parameters. Its application in the field of ECAP measurements is promising and should be further investigated.

  6. Algorithm for multi-curve-fitting with shared parameters and a possible application in evoked compound action potential measurements

    Directory of Open Access Journals (Sweden)

    Zierhofer Clemens

    2006-02-01

    Full Text Available Abstract Background Experimental results are commonly fitted by determining parameter values of suitable mathematical expressions. In case a relation exists between different data sets, the accuracy of the parameters obtained can be increased by incorporating this relationship in the fitting process instead of fitting the recordings separately. Methods An algorithm to fit multiple measured curves simultaneously was developed. The method accounts for parameters that are shared by some curves. It can be applied to either linear or nonlinear equations. Simulated noisy "measurement results" were created to compare the introduced method to the "straight forward" way of fitting the curves separately. Results The analysis of the simulated measurements confirm, that the introduced method yields more accurate parameters compared to the ones gained by fitting the measurements separately. Therefore it needs more computer time. As an example, the new fitting algorithm is applied to the measurements of the evoked compound action potentials (ECAP of the auditory nerve: This leads to promising ideas to reduce artefacts generated by the measuring process. Conclusion The introduced fitting algorithm uses the relationship between multiple measurement results to increase the accuracy of the parameters. Its application in the field of ECAP measurements is promising and should be further investigated.

  7. A combined method to estimate parameters of the thalamocortical model from a heavily noise-corrupted time series of action potential

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ruofan; Wang, Jiang; Deng, Bin, E-mail: dengbin@tju.edu.cn; Liu, Chen; Wei, Xile [Department of Electrical and Automation Engineering, Tianjin University, Tianjin (China); Tsang, K. M.; Chan, W. L. [Department of Electrical Engineering, The Hong Kong Polytechnic University, Kowloon (Hong Kong)

    2014-03-15

    A combined method composing of the unscented Kalman filter (UKF) and the synchronization-based method is proposed for estimating electrophysiological variables and parameters of a thalamocortical (TC) neuron model, which is commonly used for studying Parkinson's disease for its relay role of connecting the basal ganglia and the cortex. In this work, we take into account the condition when only the time series of action potential with heavy noise are available. Numerical results demonstrate that not only this method can estimate model parameters from the extracted time series of action potential successfully but also the effect of its estimation is much better than the only use of the UKF or synchronization-based method, with a higher accuracy and a better robustness against noise, especially under the severe noise conditions. Considering the rather important role of TC neuron in the normal and pathological brain functions, the exploration of the method to estimate the critical parameters could have important implications for the study of its nonlinear dynamics and further treatment of Parkinson's disease.

  8. Screening action potentials: The power of light

    Directory of Open Access Journals (Sweden)

    Lars eKaestner

    2011-07-01

    Full Text Available Action potentials reflect the concerted activity of all electrogenic constituents in the plasma membrane during the excitation of a cell. Therefore, the action potential is an integrated readout and a promising parameter to detect electrophysiological failures or modifications thereof in diagnosis as well as in drug screens. Cellular action potentials can be recorded by optical approaches. To fulfill the pre-requirements to scale up for e.g. pharmacological screens the following preparatory work has to be provided: (i model cells under investigation need to represent target cells in the best possible manner; (ii optical sensors that can be either small molecule dyes or genetically encoded potential probes need to provide a reliable readout with minimal interaction with the naive behavior of the cells and (iii devices need to be capable to stimulate the cells, read out the signals with the appropriate speed as well as provide the capacity for a sufficient throughput. Here we discuss several scenarios for all three categories in the field of cardiac physiology and pharmacology and provide a perspective to use the power of light in screening cardiac action potentials.

  9. Potential biomarker of metformin action.

    Science.gov (United States)

    He, Ling; Meng, Shumei; Germain-Lee, Emily L; Radovick, Sally; Wondisford, Fredric E

    2014-06-01

    Metformin is a first-line, anti-diabetic agent prescribed to over 150 million people worldwide. The main effect of metformin is to suppress glucose production in the liver; however, there is no reliable biomarker to assess the effectiveness of metformin administration. Our previous studies have shown that phosphorylation of CBP at S436 is important for the regulation of hepatic glucose production by metformin. In current study, we found that CBP could be phosphorylated in white blood cells (WBCs), and CBP phosphorylation in the liver and in WBCs of mice had a similar pattern of change during a fasting time course experiment. These data suggests that CBP phosphorylation in WBCs may be used as a biomarker of metformin action in the liver. © 2014 Society for Endocrinology.

  10. Simulation of action potential propagation in plants.

    Science.gov (United States)

    Sukhov, Vladimir; Nerush, Vladimir; Orlova, Lyubov; Vodeneev, Vladimir

    2011-12-21

    Action potential is considered to be one of the primary responses of a plant to action of various environmental factors. Understanding plant action potential propagation mechanisms requires experimental investigation and simulation; however, a detailed mathematical model of plant electrical signal transmission is absent. Here, the mathematical model of action potential propagation in plants has been worked out. The model is a two-dimensional system of excitable cells; each of them is electrically coupled with four neighboring ones. Ion diffusion between excitable cell apoplast areas is also taken into account. The action potential generation in a single cell has been described on the basis of our previous model. The model simulates active and passive signal transmission well enough. It has been used to analyze theoretically the influence of cell to cell electrical conductivity and H(+)-ATPase activity on the signal transmission in plants. An increase in cell to cell electrical conductivity has been shown to stimulate an increase in the length constant, the action potential propagation velocity and the temperature threshold, while the membrane potential threshold being weakly changed. The growth of H(+)-ATPase activity has been found to induce the increase of temperature and membrane potential thresholds and the reduction of the length constant and the action potential propagation velocity. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Introducing the Action Potential to Psychology Students

    Science.gov (United States)

    Simon-Dack, Stephanie L.

    2014-01-01

    For this simple active learning technique for teaching, students are assigned "roles" and act out the process of the action potential (AP), including the firing threshold, ion-specific channels for ions to enter and leave the cell, diffusion, and the refractory period. Pre-post test results indicated that students demonstrated increased…

  12. Computer Simulation of the Neuronal Action Potential.

    Science.gov (United States)

    Solomon, Paul R.; And Others

    1988-01-01

    A series of computer simulations of the neuronal resting and action potentials are described. Discusses the use of simulations to overcome the difficulties of traditional instruction, such as blackboard illustration, which can only illustrate these events at one point in time. Describes systems requirements necessary to run the simulations.…

  13. Conduction velocity of antigravity muscle action potentials.

    Science.gov (United States)

    Christova, L; Kosarov, D; Christova, P

    1992-01-01

    The conduction velocity of the impulses along the muscle fibers is one of the parameters of the extraterritorial potentials of the motor units allowing for the evaluation of the functional state of the muscles. There are no data about the conduction velocities of antigravity muscleaction potentials. In this paper we offer a method for measuring conduction velocity of potentials of single MUs and the averaged potentials of the interference electromiogram (IEMG) lead-off by surface electrodes from mm. sternocleidomastoideus, trapezius, deltoideus (caput laterale) and vastus medialis. The measured mean values of the conduction velocity of antigravity muscles potentials can be used for testing the functional state of the muscles.

  14. A physical action potential generator: design, implementation and evaluation.

    Science.gov (United States)

    Latorre, Malcolm A; Chan, Adrian D C; Wårdell, Karin

    2015-01-01

    The objective was to develop a physical action potential generator (Paxon) with the ability to generate a stable, repeatable, programmable, and physiological-like action potential. The Paxon has an equivalent of 40 nodes of Ranvier that were mimicked using resin embedded gold wires (Ø = 20 μm). These nodes were software controlled and the action potentials were initiated by a start trigger. Clinically used Ag-AgCl electrodes were coupled to the Paxon for functional testing. The Paxon's action potential parameters were tunable using a second order mathematical equation to generate physiologically relevant output, which was accomplished by varying the number of nodes involved (1-40 in incremental steps of 1) and the node drive potential (0-2.8 V in 0.7 mV steps), while keeping a fixed inter-nodal timing and test electrode configuration. A system noise floor of 0.07 ± 0.01 μV was calculated over 50 runs. A differential test electrode recorded a peak positive amplitude of 1.5 ± 0.05 mV (gain of 40x) at time 196.4 ± 0.06 ms, including a post trigger delay. The Paxon's programmable action potential like signal has the possibility to be used as a validation test platform for medical surface electrodes and their attached systems.

  15. Action potentials: to the nucleus and beyond.

    Science.gov (United States)

    Saha, Ramendra N; Dudek, Serena M

    2008-04-01

    The neuronal nucleus is now widely accepted as playing a vital role in maintaining long-term changes in synaptic effectiveness. To act, however, the nucleus must be appropriately relayed with information regarding the latest round of synaptic plasticity. Several constraints of doing so in a neuron pertain to the often significant spatial distance of synapses from the nucleus and the number of synapses required for such a signal to reach functional levels in the nucleus. Largely based on the sensitivity of transcriptional responses to NMDA receptor antagonists, it has been postulated that the signals are physically relayed by biochemical messengers from the synapse to the nucleus. Alternatively, a second, less often considered but equally viable method of signal transduction may be initiated by action potentials generated proximal to the nucleus, wherefrom the signal can be relayed directly by calcium or indirectly by biochemical second messengers. We consider action potential-dependent signaling to the nucleus to have its own computational advantages over the synapse-to-nucleus signal for some functions. This minireview summarizes the logic and experimental support for these two modes of signaling and attempts to validate the action potential model as playing an important role in transcriptional regulation relating specifically to long-term synaptic plasticity.

  16. [Patterns of action potential firing in cortical neurons of neonatal mice and their electrophysiological property].

    Science.gov (United States)

    Furong, Liu; Shengtian, L I

    2016-05-25

    To investigate patterns of action potential firing in cortical heurons of neonatal mice and their electrophysiological properties. The passive and active membrane properties of cortical neurons from 3-d neonatal mice were observed by whole-cell patch clamp with different voltage and current mode. Three patterns of action potential firing were identified in response to depolarized current injection. The effects of action potential firing patterns on voltage-dependent inward and outward current were found. Neurons with three different firing patterns had different thresholds of depolarized current. In the morphology analysis of action potential, the three type neurons were different in rise time, duration, amplitude and threshold of the first action potential evoked by 80 pA current injection. The passive properties were similar in three patterns of action potential firing. These results indicate that newborn cortical neurons exhibit different patterns of action potential firing with different action potential parameters such as shape and threshold.

  17. Action potential initiation in the hodgkin-huxley model.

    Directory of Open Access Journals (Sweden)

    Lucy J Colwell

    2009-01-01

    Full Text Available A recent paper of B. Naundorf et al. described an intriguing negative correlation between variability of the onset potential at which an action potential occurs (the onset span and the rapidity of action potential initiation (the onset rapidity. This correlation was demonstrated in numerical simulations of the Hodgkin-Huxley model. Due to this antagonism, it is argued that Hodgkin-Huxley-type models are unable to explain action potential initiation observed in cortical neurons in vivo or in vitro. Here we apply a method from theoretical physics to derive an analytical characterization of this problem. We analytically compute the probability distribution of onset potentials and analytically derive the inverse relationship between onset span and onset rapidity. We find that the relationship between onset span and onset rapidity depends on the level of synaptic background activity. Hence we are able to elucidate the regions of parameter space for which the Hodgkin-Huxley model is able to accurately describe the behavior of this system.

  18. Calculation of action potential propagation in nerve fiber.

    Science.gov (United States)

    Bogatov, N M; Grigoryan, L R; Ponetaeva, E G; Sinisyn, A S

    2014-05-01

    This article introduces generalization of the action potential spreading model which considers generation of the action potential in each segment of the nerve fiber. Behavior of the impulse signal waveform during the propagation process was analyzed. A mechanism of distributed generation of the charge in nerve fiber results in decrease of phase velocity of signal spreading rate. Amplitude of the action potential decreases and pulse width increases in the action potential propagation process. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Surface deformation during an action potential in pearled cells

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    Mussel, Matan; Fillafer, Christian; Ben-Porath, Gal; Schneider, Matthias F.

    2017-11-01

    Electric pulses in biological cells (action potentials) have been reported to be accompanied by a propagating cell-surface deformation with a nanoscale amplitude. Typically, this cell surface is covered by external layers of polymer material (extracellular matrix, cell wall material, etc.). It was recently demonstrated in excitable plant cells (Chara braunii) that the rigid external layer (cell wall) hinders the underlying deformation. When the cell membrane was separated from the cell wall by osmosis, a mechanical deformation, in the micrometer range, was observed upon excitation of the cell. The underlying mechanism of this mechanical pulse has, to date, remained elusive. Herein we report that Chara cells can undergo a pearling instability, and when the pearled fragments were excited even larger and more regular cell shape changes were observed (˜10 -100 μ m in amplitude). These transient cellular deformations were captured by a curvature model that is based on three parameters: surface tension, bending rigidity, and pressure difference across the surface. In this paper these parameters are extracted by curve-fitting to the experimental cellular shapes at rest and during excitation. This is a necessary step to identify the mechanical parameters that change during an action potential.

  20. Decoupling Action Potential Bias from Cortical Local Field Potentials

    Directory of Open Access Journals (Sweden)

    Stephen V. David

    2010-01-01

    Full Text Available Neurophysiologists have recently become interested in studying neuronal population activity through local field potential (LFP recordings during experiments that also record the activity of single neurons. This experimental approach differs from early LFP studies because it uses high impendence electrodes that can also isolate single neuron activity. A possible complication for such studies is that the synaptic potentials and action potentials of the small subset of isolated neurons may contribute disproportionately to the LFP signal, biasing activity in the larger nearby neuronal population to appear synchronous and cotuned with these neurons. To address this problem, we used linear filtering techniques to remove features correlated with spike events from LFP recordings. This filtering procedure can be applied for well-isolated single units or multiunit activity. We illustrate the effects of this correction in simulation and on spike data recorded from primary auditory cortex. We find that local spiking activity can explain a significant portion of LFP power at most recording sites and demonstrate that removing the spike-correlated component can affect measurements of auditory tuning of the LFP.

  1. Flexible graphene transistors for recording cell action potentials

    Science.gov (United States)

    Blaschke, Benno M.; Lottner, Martin; Drieschner, Simon; Bonaccini Calia, Andrea; Stoiber, Karolina; Rousseau, Lionel; Lissourges, Gaëlle; Garrido, Jose A.

    2016-06-01

    Graphene solution-gated field-effect transistors (SGFETs) are a promising platform for the recording of cell action potentials due to the intrinsic high signal amplification of graphene transistors. In addition, graphene technology fulfills important key requirements for in-vivo applications, such as biocompability, mechanical flexibility, as well as ease of high density integration. In this paper we demonstrate the fabrication of flexible arrays of graphene SGFETs on polyimide, a biocompatible polymeric substrate. We investigate the transistor’s transconductance and intrinsic electronic noise which are key parameters for the device sensitivity, confirming that the obtained values are comparable to those of rigid graphene SGFETs. Furthermore, we show that the devices do not degrade during repeated bending and the transconductance, governed by the electronic properties of graphene, is unaffected by bending. After cell culture, we demonstrate the recording of cell action potentials from cardiomyocyte-like cells with a high signal-to-noise ratio that is higher or comparable to competing state of the art technologies. Our results highlight the great capabilities of flexible graphene SGFETs in bioelectronics, providing a solid foundation for in-vivo experiments and, eventually, for graphene-based neuroprosthetics.

  2. Is action potential threshold lowest in the axon?

    NARCIS (Netherlands)

    Kole, Maarten H. P.; Stuart, Greg J.

    2008-01-01

    Action potential threshold is thought to be lowest in the axon, but when measured using conventional techniques, we found that action potential voltage threshold of rat cortical pyramidal neurons was higher in the axon than at other neuronal locations. In contrast, both current threshold and voltage

  3. Re-modeling Chara action potential: II. The action potential form under salinity stress

    Directory of Open Access Journals (Sweden)

    Mary Jane Beilby

    2017-04-01

    Full Text Available In part I we established Thiel-Beilby model of the Chara action potential (AP. In part II the AP is investigated in detail at the time of saline stress. Even very short exposure of salt-sensitive Chara cells to artificial pond water with 50 mM NaCl (Saline APW modified the AP threshold and drastically altered the AP form. Detailed modeling of 14 saline APs from 3 cells established that both the Ca2+ pump and the Ca2+ channels on internal stores seem to be affected, with the changes sometimes cancelling and sometimes re-enforcing each other, leading to APs with long durations and very complex forms. The exposure to salinity offers further insights into AP mechanism and suggests future experiments. The prolonged APs lead to greater loss of chloride and potassium ions, compounding the effects of saline stress.

  4. Action potential propagation: ion current or intramembrane electric field?

    Science.gov (United States)

    Martí, Albert; Pérez, Juan J; Madrenas, Jordi

    2018-01-01

    The established action potential propagation mechanisms do not satisfactorily explain propagation on myelinated axons given the current knowledge of biological channels and membranes. The flow across ion channels presents two possible effects: the electric potential variations across the lipid bilayers (action potential) and the propagation of an electric field through the membrane inner part. The proposed mechanism is based on intra-membrane electric field propagation, this propagation can explain the action potential saltatory propagation and its constant delay independent of distance between Ranvier nodes in myelinated axons.

  5. Efficient parameterization of cardiac action potential models using a genetic algorithm

    Science.gov (United States)

    Cairns, Darby I.; Fenton, Flavio H.; Cherry, E. M.

    2017-09-01

    Finding appropriate values for parameters in mathematical models of cardiac cells is a challenging task. Here, we show that it is possible to obtain good parameterizations in as little as 30-40 s when as many as 27 parameters are fit simultaneously using a genetic algorithm and two flexible phenomenological models of cardiac action potentials. We demonstrate how our implementation works by considering cases of "model recovery" in which we attempt to find parameter values that match model-derived action potential data from several cycle lengths. We assess performance by evaluating the parameter values obtained, action potentials at fit and non-fit cycle lengths, and bifurcation plots for fidelity to the truth as well as consistency across different runs of the algorithm. We also fit the models to action potentials recorded experimentally using microelectrodes and analyze performance. We find that our implementation can efficiently obtain model parameterizations that are in good agreement with the dynamics exhibited by the underlying systems that are included in the fitting process. However, the parameter values obtained in good parameterizations can exhibit a significant amount of variability, raising issues of parameter identifiability and sensitivity. Along similar lines, we also find that the two models differ in terms of the ease of obtaining parameterizations that reproduce model dynamics accurately, most likely reflecting different levels of parameter identifiability for the two models.

  6. Modeling of action potential generation in NG108-15 cells.

    Science.gov (United States)

    Molnar, Peter; Hickman, James J

    2014-01-01

    In order to explore the possibility of identifying toxins based on their effect on the shape of action potentials, we created a computer model of the action potential generation in NG108-15 cells (a neuroblastoma/glioma hybrid cell line). To generate the experimental data for model validation, voltage-dependent sodium, potassium and high-threshold calcium currents, as well as action potentials, were recorded from NG108-15 cells with conventional whole-cell patch-clamp methods. Based on the classic Hodgkin-Huxley formalism and the linear thermodynamic description of the rate constants, ion-channel parameters were estimated using an automatic fitting method. Utilizing the established parameters, action potentials were generated using the Hodgkin-Huxley formalism and were fitted to the recorded action potentials. To demonstrate the applicability of the method for toxin detection and discrimination, the effect of tetrodotoxin (a sodium channel blocker) and tefluthrin (a pyrethroid that is a sodium channel opener) were studied. The two toxins affected the shape of the action potentials differently, and their respective effects were identified based on the predicted changes in the fitted parameters.

  7. Quadratic adaptive algorithm for solving cardiac action potential models.

    Science.gov (United States)

    Chen, Min-Hung; Chen, Po-Yuan; Luo, Ching-Hsing

    2016-10-01

    An adaptive integration method is proposed for computing cardiac action potential models accurately and efficiently. Time steps are adaptively chosen by solving a quadratic formula involving the first and second derivatives of the membrane action potential. To improve the numerical accuracy, we devise an extremum-locator (el) function to predict the local extremum when approaching the peak amplitude of the action potential. In addition, the time step restriction (tsr) technique is designed to limit the increase in time steps, and thus prevent the membrane potential from changing abruptly. The performance of the proposed method is tested using the Luo-Rudy phase 1 (LR1), dynamic (LR2), and human O'Hara-Rudy dynamic (ORd) ventricular action potential models, and the Courtemanche atrial model incorporating a Markov sodium channel model. Numerical experiments demonstrate that the action potential generated using the proposed method is more accurate than that using the traditional Hybrid method, especially near the peak region. The traditional Hybrid method may choose large time steps near to the peak region, and sometimes causes the action potential to become distorted. In contrast, the proposed new method chooses very fine time steps in the peak region, but large time steps in the smooth region, and the profiles are smoother and closer to the reference solution. In the test on the stiff Markov ionic channel model, the Hybrid blows up if the allowable time step is set to be greater than 0.1ms. In contrast, our method can adjust the time step size automatically, and is stable. Overall, the proposed method is more accurate than and as efficient as the traditional Hybrid method, especially for the human ORd model. The proposed method shows improvement for action potentials with a non-smooth morphology, and it needs further investigation to determine whether the method is helpful during propagation of the action potential. Copyright © 2016 Elsevier Ltd. All rights

  8. Fiber Optic Detection of Action Potentials in Axons

    National Research Council Canada - National Science Library

    Smela, Elisabeth

    2006-01-01

    In prior exploratory research, we had designed a fiber optic sensor utilizing a long period Bragg grating for the purpose of detecting action potentials in axons optically, through a change in index...

  9. Synchronization of action potentials during low-magnesium-induced bursting

    Science.gov (United States)

    Johnson, Sarah E.; Hudson, John L.

    2015-01-01

    The relationship between mono- and polysynaptic strength and action potential synchronization was explored using a reduced external Mg2+ model. Single and dual whole cell patch-clamp recordings were performed in hippocampal cultures in three concentrations of external Mg2+. In decreased Mg2+ medium, the individual cells transitioned to spontaneous bursting behavior. In lowered Mg2+ media the larger excitatory synaptic events were observed more frequently and fewer transmission failures occurred, suggesting strengthened synaptic transmission. The event synchronization was calculated for the neural action potentials of the cell pairs, and it increased in media where Mg2+ concentration was lowered. Analysis of surrogate data where bursting was present, but no direct or indirect connections existed between the neurons, showed minimal action potential synchronization. This suggests the synchronization of action potentials is a product of the strengthening synaptic connections within neuronal networks. PMID:25609103

  10. Neuronal oscillations enhance stimulus discrimination by ensuring action potential precision

    DEFF Research Database (Denmark)

    Schaefer, Andreas T; Angelo, Kamilla; Spors, Hartwig

    2006-01-01

    generated membrane potential oscillations dramatically improve action potential (AP) precision by removing the membrane potential variance associated with jitter-accumulating trains of APs. This increased AP precision occurred irrespective of cell type and--at oscillation frequencies ranging from 3 to 65 Hz...

  11. Role of Sodium Channel on Cardiac Action Potential

    OpenAIRE

    S. H. Sabzpoushan; A. Faghani Ghodrat

    2012-01-01

    Sudden cardiac death is a major cause of death worldwide. In most cases, it's caused by abnormal action potential propagation that leads to cardiac arrhythmia. The aim of this article is to study the abnormal action potential propagation through sodium ion concentration variations. We use a new electrophysiological model that is both detailed and computationally efficient. This efficient model is based on the partial differential equation method. The central finite difference method is used f...

  12. Actions, Objectives & Concerns. Human Parameters for Architectural Design.

    Science.gov (United States)

    Lasswell, Thomas E.; And Others

    An experiment conducted at California State College, Los Angeles, to test the value of social-psychological research in defining building needs is described. The problems of how to identify and synthesize the disparate objectives, concerns and actions of the groups who use or otherwise have an interest in large and complex buildings is discussed.…

  13. Coupled Learning of Action Parameters and Forward Models for Manipulation

    Science.gov (United States)

    2016-10-09

    rules, predicting high-level, abstract Both authors are with the Robotics and Biology Laboratory , Technische Universität Berlin, Germany. We gratefully...collection: In each scenario, the robot interacts with cabinets in different states (open, locked, closed, un- locked) by randomly selecting the handle , box...mechanisms.) Third, in some training samples an action evokes undesired side effects; e.g., in the box-and- handle scenario the robot simultaneously

  14. Short infrared laser pulses block action potentials in neurons

    Science.gov (United States)

    Walsh, Alex J.; Tolstykh, Gleb P.; Martens, Stacey L.; Ibey, Bennett L.; Beier, Hope T.

    2017-02-01

    Short infrared laser pulses have many physiological effects on cells including the ability to stimulate action potentials in neurons. Here we show that short infrared laser pulses can also reversibly block action potentials. Primary rat hippocampal neurons were transfected with the Optopatch2 plasmid, which contains both a blue-light activated channel rhodopsin (CheRiff) and a red-light fluorescent membrane voltage reporter (QuasAr2). This optogenetic platform allows robust stimulation and recording of action potential activity in neurons in a non-contact, low noise manner. For all experiments, QuasAr2 was imaged continuously on a wide-field fluorescent microscope using a Krypton laser (647 nm) as the excitation source and an EMCCD camera operating at 1000 Hz to collect emitted fluorescence. A co-aligned Argon laser (488 nm, 5 ms at 10Hz) provided activation light for CheRiff. A 200 mm fiber delivered infrared light locally to the target neuron. Reversible action potential block in neurons was observed following a short infrared laser pulse (0.26-0.96 J/cm2; 1.37-5.01 ms; 1869 nm), with the block persisting for more than 1 s with exposures greater than 0.69 J/cm2. Action potential block was sustained for 30 s with the short infrared laser pulsed at 1-7 Hz. Full recovery of neuronal activity was observed 5-30s post-infrared exposure. These results indicate that optogenetics provides a robust platform for the study of action potential block and that short infrared laser pulses can be used for non-contact, reversible action potential block.

  15. Compound sensory action potential in normal and pathological human nerves

    DEFF Research Database (Denmark)

    Krarup, Christian

    2004-01-01

    The compound sensory nerve action potential (SNAP) is the result of phase summation and cancellation of single fiber potentials (SFAPs) with amplitudes that depend on fiber diameter, and the amplitude and shape of the SNAP is determined by the distribution of fiber diameters. Conduction velocities...... at different conduction distances are determined by summation of SFAPs of varying fiber diameters, and differ in this respect, also, from the compound muscle action potential (CMAP) for which conduction velocities are determined by the very fastest fibers in the nerve. The effect and extent of temporal...

  16. Compound sensory action potential in normal and pathological human nerves

    DEFF Research Database (Denmark)

    Krarup, Christian

    2004-01-01

    The compound sensory nerve action potential (SNAP) is the result of phase summation and cancellation of single fiber potentials (SFAPs) with amplitudes that depend on fiber diameter, and the amplitude and shape of the SNAP is determined by the distribution of fiber diameters. Conduction velocitie...

  17. Role of Sodium Channel on Cardiac Action Potential

    Directory of Open Access Journals (Sweden)

    S. H. Sabzpoushan

    2012-06-01

    Full Text Available Sudden cardiac death is a major cause of death worldwide. In most cases, it's caused by abnormal action potential propagation that leads to cardiac arrhythmia. The aim of this article is to study the abnormal action potential propagation through sodium ion concentration variations. We use a new electrophysiological model that is both detailed and computationally efficient. This efficient model is based on the partial differential equation method. The central finite difference method is used for numerical solving of the two-dimensional (2D wave propagation equation. Simulations are implemented in two stages, as a single cardiac cell and as a two-dimensional grid of cells. In both stages, the normal action potential formation in case of a single cell and it's normal propagation in case of a two-dimensional grid of cells were simulated with nominal sodium ion conductance. Then, the effect of sodium ion concentration on the action potential signal was studied by reducing the sodium ion conductance. It is concluded that reducing the sodium ion conductance, decreases both passing ability and conduction velocity of the action potential wave front.

  18. Membrane, action, and oscillatory potentials in simulated protocells

    Science.gov (United States)

    Przybylski, Aleksander T.; Stratten, Wilford P.; Syren, Robert M.; Fox, Sidney W.

    1982-12-01

    Electrical membrane potentials, oscillations, and action potentials are observed in proteinoid microspheres impaled with (3 M KCl) microelectrodes. Although effects are of greater magnitude when the vesicles contain glycerol and natural or synthetic lecithin, the results in the purely synthetic thermal protein structures are substantial, attaining 20 mV amplitude in some cases. The results add the property of electrical potential to the other known properties of proteinoid microspheres, in their role as models for protocells.

  19. A new four-parameter empirical potential energy function for ...

    Indian Academy of Sciences (India)

    A new empirical four-parameter function is proposed for the construction of potential curves of 15 stable states of diatomic molecules. The parameters are evaluated in terms of experimentally known spectroscopic constants. On comparing its performance with other functions, the proposed function is found to be simple and ...

  20. SINGLE-FIBER ACTION-POTENTIALS IN SKELETAL-MUSCLE RELATED TO RECORDING DISTANCES

    NARCIS (Netherlands)

    VANVEEN, BK; MAST, E; BUSSCHERS, R; VERLOOP, AJ; WALLINGA, W; RUTTEN, WLC; GERRITS, PO; BOOM, HBK

    Single muscle fibre action potentials (SFAPs) are considered to be functions of a bioelectrical source and electrical conductivity parameters of the medium. In most model studies SFAPs are computed as a convolution of the bioelectrical source with a transfer function. Calculated peak-to-peak

  1. Numerical investigation of action potential transmission in plants

    Directory of Open Access Journals (Sweden)

    Mariusz Pietruszka

    2014-01-01

    Full Text Available In context of a fairly concise review of recent literature and well established experimental results we reconsider the problem of action potential propagating steadily down the plant cell(s. Having adopted slightly modified Hodgkin-Huxley set of differential equations for the action potential we carried out the numerical investigation of these equations in the course of time. We argue that the Hodgkin-Huxley-Katz model for the nerve impulse can be used to describe the phenomena which take place in plants - this point of view seems to be plausible since the mechanisms involving active ionic transport across membranes from the mathematical point of view are similar. Besides, we compare in a qualitative way our theoretical outcomes with typical experimental results for the action potentials which arise as the reaction of plants to electrical, mechanical and light stimuli. Moreover, we point out the relevance of the sequence of events during the pulse with the appropriate ionic fluxes.

  2. TRH regulates action potential shape in cerebral cortex pyramidal neurons.

    Science.gov (United States)

    Rodríguez-Molina, Víctor; Patiño, Javier; Vargas, Yamili; Sánchez-Jaramillo, Edith; Joseph-Bravo, Patricia; Charli, Jean-Louis

    2014-07-07

    Thyrotropin releasing hormone (TRH) is a neuropeptide with a wide neural distribution and a variety of functions. It modulates neuronal electrophysiological properties, including resting membrane potential, as well as excitatory postsynaptic potential and spike frequencies. We explored, with whole-cell patch clamp, TRH effect on action potential shape in pyramidal neurons of the sensorimotor cortex. TRH reduced spike and after hyperpolarization amplitudes, and increased spike half-width. The effect varied with dose, time and cortical layer. In layer V, 0.5µM of TRH induced a small increase in spike half-width, while 1 and 5µM induced a strong but transient change in spike half-width, and amplitude; after hyperpolarization amplitude was modified at 5µM of TRH. Cortical layers III and VI neurons responded intensely to 0.5µM TRH; layer II neurons response was small. The effect of 1µM TRH on action potential shape in layer V neurons was blocked by G-protein inhibition. Inhibition of the activity of the TRH-degrading enzyme pyroglutamyl peptidase II (PPII) reproduced the effect of TRH, with enhanced spike half-width. Many cortical PPII mRNA+ cells were VGLUT1 mRNA+, and some GAD mRNA+. These data show that TRH regulates action potential shape in pyramidal cortical neurons, and are consistent with the hypothesis that PPII controls its action in this region. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Uncertainty propagation in nerve impulses through the action potential mechanism

    NARCIS (Netherlands)

    A. Torres Valderrama (Aldemar); J.A.S. Witteveen (Jeroen); M.I. Navarro Jimenez (Maria); J.G. Blom (Joke)

    2015-01-01

    textabstractWe investigate the propagation of probabilistic uncertainty through the action potential mechanism in nerve cells. Using the Hodgkin-Huxley (H-H) model and Stochastic Collocation on Sparse Grids, we obtain an accurate probabilistic interpretation of the deterministic dynamics of the

  4. Compound muscle action potentials in newborn infants with spina bifida.

    NARCIS (Netherlands)

    Geerdink, N.; Pasman, J.W.; Rotteveel, J.J.; Roeleveld, N.; Mullaart, R.A.

    2008-01-01

    The aim of this study was to investigate the relationship between compound muscle action potentials (CMAPs) and neurological impairment in newborn infants with spina bifida. Thirty-one newborn infants (17 males, 14 females, mean gestational age 39 wks [SD 2]; mean birthweight 3336 g [SD 496]) with

  5. Arsenic Trioxide Modulates the Central Snail Neuron Action Potential

    Directory of Open Access Journals (Sweden)

    Guan-Ling Lu

    2009-09-01

    Conclusion: As2O3 at 10 mM elicits BoPs in central snail neurons and this effect may relate to the PLC activity of the neuron, rather than protein kinase A activity, or calcium influxes of the neuron. As2O3 at higher concentration irreversibly abolishes the spontaneous action potentials of the neuron.

  6. Acute nerve compression and the compound muscle action potential

    Directory of Open Access Journals (Sweden)

    Baylor Kelly

    2008-01-01

    Full Text Available Abstract Detecting acute nerve compression using neurophysiologic studies is an important part of the practice of clinical intra-operative neurophysiology. The goal of this paper was to study the changes in the compound muscle action potential (CMAP during acute mechanical compression. This is the type of injury most likely to occur during surgery. Thus, understanding the changes in the CMAP during this type of injury will be useful in the detection and prevention using intra-operative neurophysiologic monitoring. The model involved compression of the hamster sciatic nerve over a region of 1.3 mm with pressures up to 2000 mmHg for times on the order of 3 minutes. In this model CMAP amplitude dropped to 50% of its baseline value when a pressure of roughly 1000 mmHg is applied while, at the same time, nerve conduction velocities decline by only 5%. The ability to detect statistically significant changes in the CMAP at low force levels using other descriptors of the CMAP including duration, latency variation, etc alone or in conjunction with amplitude and velocity measures was investigated. However, these other parameters did not allow for earlier detection of significant changes. This study focused on a model in which nerve injury on a short time scale is purely mechanical in origin. It demonstrated that a pure compression injury produced large changes in CMAP amplitude prior to large changes in conduction velocity. On the other hand, ischemic and stretch injuries are associated with larger changes in conduction velocity for a given value of CMAP amplitude reduction.

  7. GUP parameter from quantum corrections to the Newtonian potential

    Energy Technology Data Exchange (ETDEWEB)

    Scardigli, Fabio, E-mail: fabio@phys.ntu.edu.tw [Dipartimento di Matematica, Politecnico di Milano, Piazza L. da Vinci 32, 20133 Milano (Italy); Department of Applied Mathematics, University of Waterloo, Ontario N2L 3G1 (Canada); Yukawa Institute for Theoretical Physics, Kyoto University, Kyoto 606-8502 (Japan); Lambiase, Gaetano, E-mail: lambiase@sa.infn.it [Dipartimento di Fisica “E.R. Caianiello”, Universita' di Salerno, I-84084 Fisciano (Italy); INFN – Gruppo Collegato di Salerno (Italy); Vagenas, Elias C., E-mail: elias.vagenas@ku.edu.kw [Theoretical Physics Group, Department of Physics, Kuwait University, P.O. Box 5969, Safat 13060 (Kuwait)

    2017-04-10

    We propose a technique to compute the deformation parameter of the generalized uncertainty principle by using the leading quantum corrections to the Newtonian potential. We just assume General Relativity as theory of Gravitation, and the thermal nature of the GUP corrections to the Hawking spectrum. With these minimal assumptions our calculation gives, to first order, a specific numerical result. The physical meaning of this value is discussed, and compared with the previously obtained bounds on the generalized uncertainty principle deformation parameter.

  8. Studies on the Action Potential From a Thermodynamic Perspective

    DEFF Research Database (Denmark)

    Wang, Tian

    of the nerve impulses, while the measured temperature change during the oscillation reaction suggests that there are a reversible adiabatic process and a dissipative process. (3) Local anesthetic e↵ect on nerves is studied. Local anesthetic lidocaine causes a significant stimulus threshold shift of the action...... and nerves with ganglia. (2) Attempts have been made to measure the temperature change associated with an action potential as well as an oscillation reaction (Briggs-Rauscher reaction) that shares the adiabatic feature. It turns out that some practical issues need to be solved for the temperature measurement...

  9. Calcium-Induced calcium release during action potential firing in developing inner hair cells.

    Science.gov (United States)

    Iosub, Radu; Avitabile, Daniele; Grant, Lisa; Tsaneva-Atanasova, Krasimira; Kennedy, Helen J

    2015-03-10

    In the mature auditory system, inner hair cells (IHCs) convert sound-induced vibrations into electrical signals that are relayed to the central nervous system via auditory afferents. Before the cochlea can respond to normal sound levels, developing IHCs fire calcium-based action potentials that disappear close to the onset of hearing. Action potential firing triggers transmitter release from the immature IHC that in turn generates experience-independent firing in auditory neurons. These early signaling events are thought to be essential for the organization and development of the auditory system and hair cells. A critical component of the action potential is the rise in intracellular calcium that activates both small conductance potassium channels essential during membrane repolarization, and triggers transmitter release from the cell. Whether this calcium signal is generated by calcium influx or requires calcium-induced calcium release (CICR) is not yet known. IHCs can generate CICR, but to date its physiological role has remained unclear. Here, we used high and low concentrations of ryanodine to block or enhance CICR to determine whether calcium release from intracellular stores affected action potential waveform, interspike interval, or changes in membrane capacitance during development of mouse IHCs. Blocking CICR resulted in mixed action potential waveforms with both brief and prolonged oscillations in membrane potential and intracellular calcium. This mixed behavior is captured well by our mathematical model of IHC electrical activity. We perform two-parameter bifurcation analysis of the model that predicts the dependence of IHCs firing patterns on the level of activation of two parameters, the SK2 channels activation and CICR rate. Our data show that CICR forms an important component of the calcium signal that shapes action potentials and regulates firing patterns, but is not involved directly in triggering exocytosis. These data provide important insights

  10. [Effect of stimulating pulse width on the threshold of electrically evoked compound action potential].

    Science.gov (United States)

    Yu, Zhongde; Xiao, Ling; Li, Ping; Meng, Li; Zi, Rui; Fei, Xingbo

    2014-12-01

    This paper discusses the relationship between stimulating pulse width and the threshold of electrically evoked compound action potential (ECAP). Firstly, the rheobase and chronaxy from strength-duration curve of nerve fiber was computed using the shepherd's experiment results. Secondly, based on the relationship between ECAP and the action potential of nerve fiber, a mathematical expression to describe the relationship between stimulating pulse width and ECAP threshold was proposed. Thirdly, the parameters were obtained and the feasibility was proved to the expression with the results of experiment using guinea pigs. Research result showed that with ECAP compared to the action potential of nerve fiber, their threshold function relationship with stimulating pulse width was similar, and rheobase from the former was an order smaller in the magnitude than the latter, but the chronaxy was close to each other. These findings may provide meaningful guidance to clinical ECAP measurement and studying speech processing strategies of cochlear implant.

  11. A new four-parameter empirical potential energy function for ...

    Indian Academy of Sciences (India)

    A new four-parameter empirical potential energy function for diatomic molecules. M RAFI. 2,∗. , REEM AL-TUWIRQI. 1. , HANAA FARHAN. 1 and I A KHAN. 2. 1. Department of Physics, Faculty of Science, P.O. Box 16751, Jeddah 21474, Saudi Arabia. 2. Department of Physics, University of Karachi, Karachi 75270, Pakistan.

  12. The Electrically Evoked Compound Action Potential: From Laboratory to Clinic.

    Science.gov (United States)

    He, Shuman; Teagle, Holly F B; Buchman, Craig A

    2017-01-01

    The electrically evoked compound action potential (eCAP) represents the synchronous firing of a population of electrically stimulated auditory nerve fibers. It can be directly recorded on a surgically exposed nerve trunk in animals or from an intra-cochlear electrode of a cochlear implant. In the past two decades, the eCAP has been widely recorded in both animals and clinical patient populations using different testing paradigms. This paper provides an overview of recording methodologies and response characteristics of the eCAP, as well as its potential applications in research and clinical situations. Relevant studies are reviewed and implications for clinicians are discussed.

  13. Cortical Interneuron Subtypes Vary in Their Axonal Action Potential Properties

    Science.gov (United States)

    Casale, Amanda E.; Foust, Amanda J.; Bal, Thierry

    2015-01-01

    The role of interneurons in cortical microcircuits is strongly influenced by their passive and active electrical properties. Although different types of interneurons exhibit unique electrophysiological properties recorded at the soma, it is not yet clear whether these differences are also manifested in other neuronal compartments. To address this question, we have used voltage-sensitive dye to image the propagation of action potentials into the fine collaterals of axons and dendrites in two of the largest cortical interneuron subtypes in the mouse: fast-spiking interneurons, which are typically basket or chandelier neurons; and somatostatin containing interneurons, which are typically regular spiking Martinotti cells. We found that fast-spiking and somatostatin-expressing interneurons differed in their electrophysiological characteristics along their entire dendrosomatoaxonal extent. The action potentials generated in the somata and axons, including axon collaterals, of somatostatin-expressing interneurons are significantly broader than those generated in the same compartments of fast-spiking inhibitory interneurons. In addition, action potentials back-propagated into the dendrites of somatostatin-expressing interneurons much more readily than fast-spiking interneurons. Pharmacological investigations suggested that axonal action potential repolarization in both cell types depends critically upon Kv1 channels, whereas the axonal and somatic action potentials of somatostatin-expressing interneurons also depend on BK Ca2+-activated K+ channels. These results indicate that the two broad classes of interneurons studied here have expressly different subcellular physiological properties, allowing them to perform unique computational roles in cortical circuit operations. SIGNIFICANCE STATEMENT Neurons in the cerebral cortex are of two major types: excitatory and inhibitory. The proper balance of excitation and inhibition in the brain is critical for its operation. Neurons

  14. GUP parameter from quantum corrections to the Newtonian potential

    Directory of Open Access Journals (Sweden)

    Fabio Scardigli

    2017-04-01

    Full Text Available We propose a technique to compute the deformation parameter of the generalized uncertainty principle by using the leading quantum corrections to the Newtonian potential. We just assume General Relativity as theory of Gravitation, and the thermal nature of the GUP corrections to the Hawking spectrum. With these minimal assumptions our calculation gives, to first order, a specific numerical result. The physical meaning of this value is discussed, and compared with the previously obtained bounds on the generalized uncertainty principle deformation parameter.

  15. Intermolecular potential parameters and combining rules determined from viscosity data

    Energy Technology Data Exchange (ETDEWEB)

    Bastien, Lucas A.J.; Price, Phillip N.; Brown, Nancy J.

    2010-05-07

    The Law of Corresponding States has been demonstrated for a number of pure substances and binary mixtures, and provides evidence that the transport properties viscosity and diffusion can be determined from a molecular shape function, often taken to be a Lennard-Jones 12-6 potential, that requires two scaling parameters: a well depth {var_epsilon}{sub ij} and a collision diameter {sigma}{sub ij}, both of which depend on the interacting species i and j. We obtain estimates for {var_epsilon}{sub ij} and {sigma}{sub ij} of interacting species by finding the values that provide the best fit to viscosity data for binary mixtures, and compare these to calculated parameters using several 'combining rules' that have been suggested for determining parameter values for binary collisions from parameter values that describe collisions of like molecules. Different combining rules give different values for {sigma}{sub ij} and {var_epsilon}{sub ij} and for some mixtures the differences between these values and the best-fit parameter values are rather large. There is a curve in ({var_epsilon}{sub ij}, {sigma}{sub ij}) space such that parameter values on the curve generate a calculated viscosity in good agreement with measurements for a pure gas or a binary mixture. The various combining rules produce couples of parameters {var_epsilon}{sub ij}, {sigma}{sub ij} that lie close to the curve and therefore generate predicted mixture viscosities in satisfactory agreement with experiment. Although the combining rules were found to underpredict the viscosity in most of the cases, Kong's rule was found to work better than the others, but none of the combining rules consistently yields parameter values near the best-fit values, suggesting that improved rules could be developed.

  16. Population of computational rabbit-specific ventricular action potential models for investigating sources of variability in cellular repolarisation.

    Science.gov (United States)

    Gemmell, Philip; Burrage, Kevin; Rodriguez, Blanca; Quinn, T Alexander

    2014-01-01

    Variability is observed at all levels of cardiac electrophysiology. Yet, the underlying causes and importance of this variability are generally unknown, and difficult to investigate with current experimental techniques. The aim of the present study was to generate populations of computational ventricular action potential models that reproduce experimentally observed intercellular variability of repolarisation (represented by action potential duration) and to identify its potential causes. A systematic exploration of the effects of simultaneously varying the magnitude of six transmembrane current conductances (transient outward, rapid and slow delayed rectifier K(+), inward rectifying K(+), L-type Ca(2+), and Na(+)/K(+) pump currents) in two rabbit-specific ventricular action potential models (Shannon et al. and Mahajan et al.) at multiple cycle lengths (400, 600, 1,000 ms) was performed. This was accomplished with distributed computing software specialised for multi-dimensional parameter sweeps and grid execution. An initial population of 15,625 parameter sets was generated for both models at each cycle length. Action potential durations of these populations were compared to experimentally derived ranges for rabbit ventricular myocytes. 1,352 parameter sets for the Shannon model and 779 parameter sets for the Mahajan model yielded action potential duration within the experimental range, demonstrating that a wide array of ionic conductance values can be used to simulate a physiological rabbit ventricular action potential. Furthermore, by using clutter-based dimension reordering, a technique that allows visualisation of multi-dimensional spaces in two dimensions, the interaction of current conductances and their relative importance to the ventricular action potential at different cycle lengths were revealed. Overall, this work represents an important step towards a better understanding of the role that variability in current conductances may play in experimentally

  17. Electrotonic and action potentials in the Venus flytrap.

    Science.gov (United States)

    Volkov, Alexander G; Vilfranc, Chrystelle L; Murphy, Veronica A; Mitchell, Colee M; Volkova, Maia I; O'Neal, Lawrence; Markin, Vladislav S

    2013-06-15

    The electrical phenomena and morphing structures in the Venus flytrap have attracted researchers since the nineteenth century. We have observed that mechanical stimulation of trigger hairs on the lobes of the Venus flytrap induces electrotonic potentials in the lower leaf. Electrostimulation of electrical circuits in the Venus flytrap can induce electrotonic potentials propagating along the upper and lower leaves. The instantaneous increase or decrease in voltage of stimulating potential generates a nonlinear electrical response in plant tissues. Any electrostimulation that is not instantaneous, such as sinusoidal or triangular functions, results in linear responses in the form of small electrotonic potentials. The amplitude and sign of electrotonic potentials depend on the polarity and the amplitude of the applied voltage. Electrical stimulation of the lower leaf induces electrical signals, which resemble action potentials, in the trap between the lobes and the midrib. The trap closes if the stimulating voltage is above the threshold level of 4.4V. Electrical responses in the Venus flytrap were analyzed and reproduced in the discrete electrical circuit. The information gained from this study can be used to elucidate the coupling of intracellular and intercellular communications in the form of electrical signals within plants. Copyright © 2013 Elsevier GmbH. All rights reserved.

  18. The Potential of Deweyan-Inspired Action Research

    Science.gov (United States)

    Stark, Jody L.

    2014-01-01

    In its broadest sense, pragmatism could be said to be the philosophical orientation of all action research. Action research is characterized by research, action, and participation grounded in democratic principles and guided by the aim of social improvement. Furthermore, action research is an active process of inquiry that does not admit…

  19. Genotoxic potential and physicochemical parameters of Sinos River, southern Brazil.

    Science.gov (United States)

    Scalon, Madalena C S; Rechenmacher, Ciliana; Siebel, Anna Maria; Kayser, Michele L; Rodrigues, Manoela T; Maluf, Sharbel W; Rodrigues, Marco Antonio S; Silva, Luciano Basso da

    2013-01-01

    The present study aimed to evaluate the physicochemical parameters and the genotoxic potential of water samples collected in the upper, middle, and lower courses of the Sinos River, southern Brazil. The comet assay was performed in the peripheral blood of fish Hyphessobrycon luetkenii exposed under laboratory conditions to water samples collected in summer and winter in three sampling sites of Sinos River. Water quality analysis demonstrated values above those described in Brazilian legislation in Parobé and Sapucaia do Sul sites, located in the middle and in the lower courses of the Sinos River, respectively. The Caraá site, located in the upper river reach, presented all the physicochemical parameters in accordance with the allowed limits in both sampling periods. Comet assay in fish revealed genotoxicity in water samples collected in the middle course site in summer and in the three sites in winter when compared to control group. Thus, the physicochemical parameters indicated that the water quality of the upper course complies with the limits set by the national guidelines, and the ecotoxicological assessment, however, indicated the presence of genotoxic agents. The present study highlights the importance of combining water physicochemical analysis and bioassays to river monitoring.

  20. Compound muscle action potential duration in critical illness neuromyopathy.

    Science.gov (United States)

    Kramer, Christopher L; Boon, Andrea J; Harper, C Michel; Goodman, Brent P

    2018-03-01

    We sought to determine the specificity of compound muscle action potential (CMAP) durations and amplitudes in a large critical illness neuromyopathy (CINM) cohort relative to controls with other neuromuscular conditions. Fifty-eight patients with CINM who had been seen over a 17-year period were retrospectively studied. Electrodiagnostic findings of the CINM cohort were compared with patients with axonal peripheral neuropathy and myopathy due to other causes. Mean CMAP durations were prolonged, and mean CMAP amplitudes were severely reduced both proximally and distally in all nerves studied in the CINM cohort relative to the control groups. The specificity of prolonged CMAP durations for CINM approached 100% if they were encountered in more than 1 nerve. Prolonged, low-amplitude CMAPs occur more frequently and with greater severity in CINM patients than in neuromuscular controls with myopathy and axonal neuropathy and are highly specific for the diagnosis of CINM. Muscle Nerve 57: 395-400, 2018. © 2017 Wiley Periodicals, Inc.

  1. Studies on the Action Potential From a Thermodynamic Perspective

    DEFF Research Database (Denmark)

    Wang, Tian

    presented in this thesis focuses on the study of the following features of nerve impulses, and interpretations from a thermodynamic view are provided. (1) Two impulses propagating toward each other are found to penetrate through each other upon collision. The penetration is found in both bundles of axons...... of the nerve impulses, while the measured temperature change during the oscillation reaction suggests that there are a reversible adiabatic process and a dissipative process. (3) Local anesthetic e↵ect on nerves is studied. Local anesthetic lidocaine causes a significant stimulus threshold shift of the action...... potential, and a slight decrease in the conduction velocity. (4) The conduction velocity of nerve impulses as a function of the diameter of the nerve is investigated with stretched ventral cords from earthworms. The velocity is found to be constant with a decrease of the diameter, indicating...

  2. Facial nerve action potentials: a study to assess waveform reliability.

    Science.gov (United States)

    Axon, P R; Ramsden, R T

    2000-11-01

    To assess the reliability of the orthodromic facial nerve action potential (FNAP), recorded from the intratemporal portion of the facial nerve on stimulation within the cerebellopontine angle. Prospective study. Tertiary referral center. Ten consecutive patients undergoing translabyrinthine resection of vestibular schwannoma. Diagnostic. Ten consecutive FNAPs were recorded on stimulation of the facial nerve within the cerebellopontine angle. The FNAP recording probe was placed directly on the nerve surface after the fallopian canal was opened at the second genu. Ten consecutive compound muscle action potentials (CMAPs) were recorded simultaneously from surface electrodes overlying the facial musculature, by use of a standardized electrode placement technique. The stimulating and recording equipment were removed (excluding CMAP surface electrodes) and reapplied, and FNAP and CMAP data were recorded for a second time (test/retest). Peak-to-peak amplitudes of all waveforms were calculated. The average FNAP peak-to-peak amplitude for all patients was larger than the CMAP peak-to-peak amplitude (2.60 mV and 1.07 mV, respectively). Random effects analysis of variance was performed to assess the individual components of variation. This showed that CMAP was less variable than FNAP for replicate error (10 consecutive FNAPs and CMAPs) and test/retest error. However, subject variance was less for FNAP, where subject variance was by far the largest contributor to overall variation. The reliability coefficient for FNAP was 0.995 and for the CMAP was 0.982, where absolute reliability is 1.0. These data confirm that the FNAP, recorded by the technique described here, is a reliable waveform when compared with the CMAP and is a valid method for assessing facial nerve function.

  3. [Multi-channel in vivo recording techniques: signal processing of action potentials and local field potentials].

    Science.gov (United States)

    Xu, Jia-Min; Wang, Ce-Qun; Lin, Long-Nian

    2014-06-25

    Multi-channel in vivo recording techniques are used to record ensemble neuronal activity and local field potentials (LFP) simultaneously. One of the key points for the technique is how to process these two sets of recorded neural signals properly so that data accuracy can be assured. We intend to introduce data processing approaches for action potentials and LFP based on the original data collected through multi-channel recording system. Action potential signals are high-frequency signals, hence high sampling rate of 40 kHz is normally chosen for recording. Based on waveforms of extracellularly recorded action potentials, tetrode technology combining principal component analysis can be used to discriminate neuronal spiking signals from differently spatially distributed neurons, in order to obtain accurate single neuron spiking activity. LFPs are low-frequency signals (lower than 300 Hz), hence the sampling rate of 1 kHz is used for LFPs. Digital filtering is required for LFP analysis to isolate different frequency oscillations including theta oscillation (4-12 Hz), which is dominant in active exploration and rapid-eye-movement (REM) sleep, gamma oscillation (30-80 Hz), which is accompanied by theta oscillation during cognitive processing, and high frequency ripple oscillation (100-250 Hz) in awake immobility and slow wave sleep (SWS) state in rodent hippocampus. For the obtained signals, common data post-processing methods include inter-spike interval analysis, spike auto-correlation analysis, spike cross-correlation analysis, power spectral density analysis, and spectrogram analysis.

  4. On the action for Weyssenhoff spin fluid and the Barbero-Immirzi parameter

    CERN Document Server

    de Berredo-Peixoto, Guilherme

    2015-01-01

    It was showed by Perez and Rovelli in 2006 that the Holst action in gravity with torsion with massless and minimally coupling Dirac fermions gives rise to the four-fermion coupling term, whose coefficient is a function of the Barbero-Immirzi (BI) parameter. This parameter is present in the Holst action, which is an object of investigation in a non-perturbative formalism of quantum gravity. The key feature is the torsion because its absence implies no effect from Holst term in dynamical equations. In this paper we consider a spin fluid (also called Weyssenhoff fluid), which is a perfect fluid that has intrinsic spin. We study the Host action in gravity with torsion and spin fluid, and we include, for completeness, minimaly coupling massive fermions.We find the equivalent action containing the same four-fermion interaction term previously calculated by Perez and Rovelli without the spin fluid, also the quadratic spin tensor term and finally an interaction term between the axial current and the spin tensor, whic...

  5. State and location dependence of action potential metabolic cost in cortical pyramidal neurons.

    Science.gov (United States)

    Hallermann, Stefan; de Kock, Christiaan P J; Stuart, Greg J; Kole, Maarten H P

    2012-06-03

    Action potential generation and conduction requires large quantities of energy to restore Na(+) and K(+) ion gradients. We investigated the subcellular location and voltage dependence of this metabolic cost in rat neocortical pyramidal neurons. Using Na(+)/K(+) charge overlap as a measure of action potential energy efficiency, we found that action potential initiation in the axon initial segment (AIS) and forward propagation into the axon were energetically inefficient, depending on the resting membrane potential. In contrast, action potential backpropagation into dendrites was efficient. Computer simulations predicted that, although the AIS and nodes of Ranvier had the highest metabolic cost per membrane area, action potential backpropagation into the dendrites and forward propagation into axon collaterals dominated energy consumption in cortical pyramidal neurons. Finally, we found that the high metabolic cost of action potential initiation and propagation down the axon is a trade-off between energy minimization and maximization of the conduction reliability of high-frequency action potentials.

  6. Action potential duration, rate of stimulation, and intracellular sodium.

    Science.gov (United States)

    Carmeliet, Edward

    2006-05-01

    In the first section of this short review the change of the cardiac action potential (APD) with the rate of stimulation under physiological conditions is described and mechanistically analyzed. A fast phase of adaptation is mainly caused by changes in gating characteristics of ionic currents, and rapid modulation of the Na(+)/Ca(2+) exchanger. The slower phase is largely conditioned by incomplete recovery from inactivation of the late Na(+) current (late I(Na)) and changes in ion concentrations of [K(+)](e), [Na(+)](i), and [Ca(2+)](i), which cause secondary changes in the permeation and the gating of ion channels and flux through transporters. In a second section, an analysis is presented of the rate dependence of APD in pathological conditions and its importance in the genesis of arrhythmias in hypertrophy, heart failure, congenital, and acquired LQT syndromes is summarized. The role of the late I(Na), Na(+), and Ca(2+) overload is emphasized. Special attention is given to the paradoxical transient lengthening of APD in LQT3 syndrome for the sudden increase in rate in this setting. The third section consists of a short commentary on Na(+) and Ca(2+) overload and drugs which block the late I(Na).

  7. Facilitation and refractoriness of the electrically evoked compound action potential.

    Science.gov (United States)

    Hey, Matthias; Müller-Deile, Joachim; Hessel, Horst; Killian, Matthijs

    2017-11-01

    In this study we aim to resolve the contributions of facilitation and refractoriness at very short pulse intervals. Measurements of the refractory properties of the electrically evoked compound action potential (ECAP) of the auditory nerve in cochlear implant (CI) users at inter pulse intervals below 300 μs are influenced by facilitation and recovery effects. ECAPs were recorded using masker pulses with a wide range of current levels relative to the probe pulse levels, for three suprathreshold probe levels and pulse intervals from 13 to 200 μs. Evoked potentials were measured for 21 CI patients by using the masked response extraction artifact cancellation procedure. During analysis of the measurements the stimulation current was not used as absolute value, but in relation to the patient's individual ECAP threshold. This enabled a more general approach to describe facilitation as a probe level independent effect. Maximum facilitation was found for all tested inter pulse intervals at masker levels near patient's individual ECAP threshold, independent from probe level. For short inter pulse intervals an increased N1P1 amplitude was measured for subthreshold masker levels down to 120 CL below patient's individual ECAP threshold in contrast to the recreated state. ECAPs recorded with inter pulse intervals up to 200 μs are influenced by facilitation and recovery. Facilitation effects are most pronounced for masker levels at or below ECAP threshold, while recovery effects increase with higher masker levels above ECAP threshold. The local maximum of the ECAP amplitude for masker levels around ECAP threshold can be explained by the mutual influence of maximum facilitation and minimal refractoriness. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  8. Accuracy of measurement in electrically evoked compound action potentials.

    Science.gov (United States)

    Hey, Matthias; Müller-Deile, Joachim

    2015-01-15

    Electrically evoked compound action potentials (ECAP) in cochlear implant (CI) patients are characterized by the amplitude of the N1P1 complex. The measurement of evoked potentials yields a combination of the measured signal with various noise components but for ECAP procedures performed in the clinical routine, only the averaged curve is accessible. To date no detailed analysis of error dimension has been published. The aim of this study was to determine the error of the N1P1 amplitude and to determine the factors that impact the outcome. Measurements were performed on 32 CI patients with either CI24RE (CA) or CI512 implants using the Software Custom Sound EP (Cochlear). N1P1 error approximation of non-averaged raw data consisting of recorded single-sweeps was compared to methods of error approximation based on mean curves. The error approximation of the N1P1 amplitude using averaged data showed comparable results to single-point error estimation. The error of the N1P1 amplitude depends on the number of averaging steps and amplification; in contrast, the error of the N1P1 amplitude is not dependent on the stimulus intensity. Single-point error showed smaller N1P1 error and better coincidence with 1/√(N) function (N is the number of measured sweeps) compared to the known maximum-minimum criterion. Evaluation of N1P1 amplitude should be accompanied by indication of its error. The retrospective approximation of this measurement error from the averaged data available in clinically used software is possible and best done utilizing the D-trace in forward masking artefact reduction mode (no stimulation applied and recording contains only the switch-on-artefact). Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Glycolysis selectively shapes the presynaptic action potential waveform.

    Science.gov (United States)

    Lujan, Brendan; Kushmerick, Christopher; Banerjee, Tania Das; Dagda, Ruben K; Renden, Robert

    2016-12-01

    Mitochondria are major suppliers of cellular energy in neurons; however, utilization of energy from glycolysis vs. mitochondrial oxidative phosphorylation (OxPhos) in the presynaptic compartment during neurotransmission is largely unknown. Using presynaptic and postsynaptic recordings from the mouse calyx of Held, we examined the effect of acute selective pharmacological inhibition of glycolysis or mitochondrial OxPhos on multiple mechanisms regulating presynaptic function. Inhibition of glycolysis via glucose depletion and iodoacetic acid (1 mM) treatment, but not mitochondrial OxPhos, rapidly altered transmission, resulting in highly variable, oscillating responses. At reduced temperature, this same treatment attenuated synaptic transmission because of a smaller and broader presynaptic action potential (AP) waveform. We show via experimental manipulation and ion channel modeling that the altered AP waveform results in smaller Ca 2+ influx, resulting in attenuated excitatory postsynaptic currents (EPSCs). In contrast, inhibition of mitochondria-derived ATP production via extracellular pyruvate depletion and bath-applied oligomycin (1 μM) had no significant effect on Ca 2+ influx and did not alter the AP waveform within the same time frame (up to 30 min), and the resultant EPSC remained unaffected. Glycolysis, but not mitochondrial OxPhos, is thus required to maintain basal synaptic transmission at the presynaptic terminal. We propose that glycolytic enzymes are closely apposed to ATP-dependent ion pumps on the presynaptic membrane. Our results indicate a novel mechanism for the effect of hypoglycemia on neurotransmission. Attenuated transmission likely results from a single presynaptic mechanism at reduced temperature: a slower, smaller AP, before and independent of any effect on synaptic vesicle release or receptor activity. Copyright © 2016 the American Physiological Society.

  10. Latent semantics of action verbs reflect phonetic parameters of intensity and emotional content

    DEFF Research Database (Denmark)

    Petersen, Michael Kai

    2015-01-01

    levels of arousal. Whereas the clustered emotional verbs seem characterized by sequences of close versus open jaw produced phonemes, generating up- or downwards shifts in formant frequencies that may influence their perceived valence. Suggesting, that the latent semantics of action verbs reflect...... already in toddlers, this study explores whether articulatory and acoustic parameters may likewise differentiate the latent semantics of action verbs. Selecting 3 X 20 emotion, face, and hand related verbs known to activate premotor areas in the brain, their mutual cosine similarities were computed using...... versus emotional expressions. Transforming the verbs into their constituent phonemes, and projecting them into an articulatory space framed by tongue height and formant frequencies, the clustered small and large size movements appear differentiated by front versus back vowels corresponding to increasing...

  11. Regional Entrepreneurship System: Development Parameters and Potential of Reconfiguration

    Directory of Open Access Journals (Sweden)

    Natalya Zinovyevna Solodilova

    2017-12-01

    Full Text Available The article deals with the development of entrepreneurship in the Russian regions. Firstly, the state of both Russian entrepreneurship, in general, and small and medium-sized business in particular is not satisfactory. Secondly, the measures implemented by the state in the field of entrepreneurship development are not sufficiently effective. To the authors’ opinion, these two facts are due, among other things, to a lack of a holistic understanding of what constitutes an institution of entrepreneurship in a spatial context. The authors propose to consider the development of regional entrepreneurship using the system approach with the scope to the regional business system. Within the proposed authors’ approach, resources, economic agents and institutions are considered as the main elements of this system. The authors substantiate that there are institutional configurations, and not simple institutions, which determine the parameters of interaction between the elements of the regional enterprise system. These elements can contribute to the enterprise processes in the territory or block them. We assume that even a region with an essential resource of business potential is not able to realize it completely until it develops an effective institutional configuration of the regional business system. In order to investigate certain parameters of the institutional configuration of the regional business system, we propose a methodology for assessing the institutional loyalty of business entities and testing this technique on the example of eighty-four constituent entities of the Russian Federation. We have concluded that, in a large part of the Russian regions, a successful implementation of strategy for the development of small and medium-sized businesses will require the transformation of the regional enterprise system on the basis of reengineering. It involves a radical redesigning the entire system, ensuring the entrepreneurial processes in a

  12. Mass Action Models Describing Extant Horizontal Transfer of Plasmids: Inferences and Parameter Sensitivities

    DEFF Research Database (Denmark)

    Smets, Barth F.; Lardon, Laurent

    2009-01-01

    Predicting the fate of horizontally transmissible elements in extant microbial communities might be facilitated by the availability of suitable mathematical models. Since the mid-1970s, mass action models have been introduced to describe the transfer of conjugal and mobilizable genetic elements...... of the outcomes to the various plasmid dynamic parameters. For our analysis, we developed a set of user-friendly MatLab® routines, which are deposited in the public domain. We hope that the availability of these routines will encourage the computationally untrained microbiologist to make use of these mathematical...

  13. Differential effects of K(+) channel blockers on frequency-dependent action potential broadening in supraoptic neurons.

    Science.gov (United States)

    Hlubek, M D; Cobbett, P

    2000-09-15

    Recordings were made from magnocellular neuroendocrine cells dissociated from the supraoptic nucleus of the adult guinea pig to determine the role of voltage gated K(+) channels in controlling the duration of action potentials and in mediating frequency-dependent action potential broadening exhibited by these neurons. The K(+) channel blockers charybdotoxin (ChTx), tetraethylammonium (TEA), and 4-aminopyridine (4-AP) increased the duration of individual action potentials indicating that multiple types of K(+) channel are important in controlling action potential duration. The effect of these K(+) channel blockers was almost completely reversed by simultaneous blockade of voltage gated Ca(2+) channels with Cd(2+). Frequency-dependent action potential broadening was exhibited by these neurons during trains of action potentials elicited by membrane depolarizing current pulses presented at 10 Hz but not at 1 Hz. 4-AP but not ChTx or TEA inhibited frequency-dependent action potential broadening indicating that frequency-dependent action potential broadening is dependent on increasing steady-state inactivation of A-type K(+) channels (which are blocked by 4-AP). A model of differential contributions of voltage gated K(+) channels and voltage gated Ca(2+) channels to frequency-dependent action potential broadening, in which an increase of Ca(2+) current during each successive action potential is permitted as a result of the increasing steady-state inactivation of A-type K(+) channels, is presented.

  14. Seismic activity parameters of the Finnish potential repository sites

    Energy Technology Data Exchange (ETDEWEB)

    Saari, J. [Fortum Engineering Oy, Vantaa (Finland)

    2000-10-01

    Posiva Oy has started a project for estimating the possible earthquake induced rock movements on the deposition holes containing canisters of spent nuclear fuel. These estimates will be made for the four investigation sites, Romuvaara, Kivetty, Olkiluoto and Haestholmen. This study deals with the current and future seismicity associated with the above mentioned sites. Seismic belts that participate the seismic behaviour of the studied sites have been identified and the magnitude-frequency distributions of these belts have been estimated. The seismic activity parameters of the sites have been deduced from the characteristics of the seismic belts in order to forecast the seismicity during the next 100,000 years. The report discusses the possible earthquakes induced by future glaciation. The seismic interpretation seems to indicate that the previous postglacial faults in Finnish Lapland have been generated in compressional environment. The orientation of the rather uniform compression has been NW-SE, which coincide with the current stress field. It seems that, although the impact of postglacial crustal rebound must have been significant, the impact of plate tectonics has been dominant. A major assumption of this study has been that future seismicity will generally resemble the current seismicity. However, when the postglacial seismicity is concerned, the magnitude-frequency distribution is likely different and the expected maximum magnitude will be higher. Maximum magnitudes of future postglacial earthquakes have been approximated by strain release examinations. Seismicity has been examined within the framework of the lineament maps, in order to associate the future significant earthquakes with active fault zones in the vicinity of the potential repository sites. (orig.)

  15. Dynamin phosphorylation controls optimization of endocytosis for brief action potential bursts

    Science.gov (United States)

    Armbruster, Moritz; Messa, Mirko; Ferguson, Shawn M; De Camilli, Pietro; Ryan, Timothy A

    2013-01-01

    Modulation of synaptic vesicle retrieval is considered to be potentially important in steady-state synaptic performance. Here we show that at physiological temperature endocytosis kinetics at hippocampal and cortical nerve terminals show a bi-phasic dependence on electrical activity. Endocytosis accelerates for the first 15–25 APs during bursts of action potential firing, after which it slows with increasing burst length creating an optimum stimulus for this kinetic parameter. We show that activity-dependent acceleration is only prominent at physiological temperature and that the mechanism of this modulation is based on the dephosphorylation of dynamin 1. Nerve terminals in which dynamin 1 and 3 have been replaced with dynamin 1 harboring dephospho- or phospho-mimetic mutations in the proline-rich domain eliminate the acceleration phase by either setting endocytosis at an accelerated state or a decelerated state, respectively. DOI: http://dx.doi.org/10.7554/eLife.00845.001 PMID:23908769

  16. Understanding the Electrical Behavior of the Action Potential in Terms of Elementary Electrical Sources

    Science.gov (United States)

    Rodriguez-Falces, Javier

    2015-01-01

    A concept of major importance in human electrophysiology studies is the process by which activation of an excitable cell results in a rapid rise and fall of the electrical membrane potential, the so-called action potential. Hodgkin and Huxley proposed a model to explain the ionic mechanisms underlying the formation of action potentials. However,…

  17. Action Potential Transfer at the Purkinje - Ventricular Junction: Role of Transitional Cells

    Science.gov (United States)

    2001-10-25

    cells on action potential transfer at the P-V junction. Using an extended version of the “model clamp” technique [6], we electrically coupled an...uncoupling followed by 6-s of coupling at any desired value of Gc, which was followed by another 2-s period of uncoupling. ACTION POTENTIAL TRANSFER AT THE...Documentation Page Report Date 25OCT2001 Report Type N/A Dates Covered (from... to) - Title and Subtitle Action Potential Transfer at the Purkinje

  18. Averaging methods for extracting representative waveforms from motor unit action potential trains.

    Science.gov (United States)

    Malanda, Armando; Navallas, Javier; Rodriguez-Falces, Javier; Rodriguez-Carreño, Ignacio; Gila, Luis

    2015-08-01

    In the context of quantitative electromyography (EMG), it is of major interest to obtain a waveform that faithfully represents the set of potentials that constitute a motor unit action potential (MUAP) train. From this waveform, various parameters can be determined in order to characterize the MUAP for diagnostic analysis. The aim of this work was to conduct a thorough, in-depth review, evaluation and comparison of state-of-the-art methods for composing waveforms representative of MUAP trains. We evaluated nine averaging methods: Ensemble (EA), Median (MA), Weighted (WA), Five-closest (FCA), MultiMUP (MMA), Split-sweep median (SSMA), Sorted (SA), Trimmed (TA) and Robust (RA) in terms of three general-purpose signal processing figures of merit (SPMF) and seven clinically-used MUAP waveform parameters (MWP). The convergence rate of the methods was assessed as the number of potentials per MUAP train (NPM) required to reach a level of performance that was not significantly improved by increasing this number. Test material comprised 78 MUAP trains obtained from the tibialis anterioris of seven healthy subjects. Error measurements related to all SPMF and MWP parameters except MUAP amplitude descended asymptotically with increasing NPM for all methods. MUAP amplitude showed a consistent bias (around 4% for EA and SA and 1-2% for the rest). MA, TA and SSMA had the lowest SPMF and MWP error figures. Therefore, these methods most accurately preserve and represent MUAP physiological information of utility in clinical medical practice. The other methods, particularly WA, performed noticeably worse. Convergence rate was similar for all methods, with NPM values averaged among the nine methods, which ranged from 10 to 40, depending on the waveform parameter evaluated. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. On the excitation of action potentials by protons and its potential implications for cholinergic transmission

    CERN Document Server

    Fillafer, Christian

    2014-01-01

    One of the most conserved mechanisms for transmission of a nerve pulse across a synapse relies on acetylcholine. Ever since the Nobel-prize winning works of Dale and Loewi, it has been assumed that acetylcholine - subsequent to its action on a postsynaptic cell - is split into inactive by-products by acetylcholinesterase. Herein, this widespread assumption is falsified. Excitable cells (Chara australis internodes), which had previously been unresponsive to acetylcholine, became acetylcholine-sensitive in presence of acetylcholinesterase. The latter was evidenced by a striking difference in cell membrane depolarisation upon exposure to 10 mM intact acetylcholine (deltaV=-2plus/minus5 mV) and its hydrolysate respectively (deltaV=81plus/minus19 mV) for 60 sec. This pronounced depolarization, which also triggered action potentials, was clearly attributed to one of the hydrolysis products: acetic acid (deltaV=87plus/minus9 mV at pH 4.0; choline ineffective in range 1-10 mM). In agreement with our findings, numerou...

  20. Consumer-Related Food Waste: Causes and Potential for Action

    DEFF Research Database (Denmark)

    Aschemann-Witzel, Jessica; Hooge, Ilona de; Amani, Pegah

    2015-01-01

    are one of the biggest sources of food waste. To successfully reduce consumer-related food waste, it is necessary to have a clear understanding of the factors influencing food waste-related consumer perceptions and behaviors. The present paper presents the results of a literature review and expert...... interviews on factors causing consumer-related food waste in households and supply chains. Results show that consumers’ motivation to avoid food waste, their management skills of food provisioning and food handling and their trade-offs between priorities have an extensive influence on their food waste...... behaviors. We identify actions that governments, societal stakeholders and retailers can undertake to reduce consumer-related food waste, highlighting that synergistic actions between all parties are most promising. Further research should focus on exploring specific food waste contexts and interactions...

  1. Adductor pollicis muscle: potential anthropometric parameter in hospitalized individuals

    Directory of Open Access Journals (Sweden)

    Teresa Cristina Abranches Rosa

    2015-07-01

    Full Text Available This study evaluated the measurement of adductor pollicis muscle thickness as a parameter for the assessment of nutritional status in patients admitted to a University Hospital in Campo Grande, Mato Grosso do Sul State. This is a prospective cross-sectional study with 64 adults and elderly patients. We evaluated the percentage of weight loss based on the usual weight, arm circumference, triceps skinfold thickness, arm muscle circumference, laboratory parameters and measurement of adductor pollicis muscle thickness. The measurements were performed only once, in the first 72 hours of hospitalization. Data were analyzed using statistical software BioEstat 5.0, with a significance level of 0.05. The average thickness of the adductor pollicis muscle was 17.5 + 5.3 mm. We found a significant negative association of muscle with age. There was a significant association between the measure of muscle and parameters such as body mass index, arm circumference, arm muscle circumference, albumin and nutritional status assessed by physical examination. The adductor pollicis muscle allows easy measurement, direct assessment, fast results, low cost and good correlation with anthropometric parameters. However, further studies should be conducted to validate this new method.

  2. Dynamics of Action Potential Initiation in the GABAergic Thalamic Reticular Nucleus In Vivo

    Science.gov (United States)

    Muñoz, Fabián; Fuentealba, Pablo

    2012-01-01

    Understanding the neural mechanisms of action potential generation is critical to establish the way neural circuits generate and coordinate activity. Accordingly, we investigated the dynamics of action potential initiation in the GABAergic thalamic reticular nucleus (TRN) using in vivo intracellular recordings in cats in order to preserve anatomically-intact axo-dendritic distributions and naturally-occurring spatiotemporal patterns of synaptic activity in this structure that regulates the thalamic relay to neocortex. We found a wide operational range of voltage thresholds for action potentials, mostly due to intrinsic voltage-gated conductances and not synaptic activity driven by network oscillations. Varying levels of synchronous synaptic inputs produced fast rates of membrane potential depolarization preceding the action potential onset that were associated with lower thresholds and increased excitability, consistent with TRN neurons performing as coincidence detectors. On the other hand the presence of action potentials preceding any given spike was associated with more depolarized thresholds. The phase-plane trajectory of the action potential showed somato-dendritic propagation, but no obvious axon initial segment component, prominent in other neuronal classes and allegedly responsible for the high onset speed. Overall, our results suggest that TRN neurons could flexibly integrate synaptic inputs to discharge action potentials over wide voltage ranges, and perform as coincidence detectors and temporal integrators, supported by a dynamic action potential threshold. PMID:22279567

  3. Estimating the Parameters of Deformation Action by Ultrasonic Surface Hardening of Metals

    Science.gov (United States)

    Rakhimyanov, Kharis M.; Rakhimyanov, Konstantin Kh; Rakhimyanov, Andrey Kh

    2017-10-01

    Developing the effective technologies of detail machining greatly depends on understanding the processes laid down in their basis. The technological methods based on electro-physical processes are considered to be attractive. These are the methods of surface plastic deforming which use the energy of ultrasonic oscillations. The peculiarities of these methods are characterized by high intensity and impulse character of the ultrasonic action. The paper presents the results of mathematical modeling of deformation processes under the impact of the ultrasonic tool on the surface layer of metals and alloys. The theoretical approach to studying the process of ultrasonic deforming allowed us to determine the mode parameters of impact and their quantitative correlations with the main characteristics of the deformation process.

  4. Latent Semantics of Action Verbs Reflect Phonetic Parameters of Intensity and Emotional Content

    Science.gov (United States)

    Petersen, Michael Kai

    2015-01-01

    Conjuring up our thoughts, language reflects statistical patterns of word co-occurrences which in turn come to describe how we perceive the world. Whether counting how frequently nouns and verbs combine in Google search queries, or extracting eigenvectors from term document matrices made up of Wikipedia lines and Shakespeare plots, the resulting latent semantics capture not only the associative links which form concepts, but also spatial dimensions embedded within the surface structure of language. As both the shape and movements of objects have been found to be associated with phonetic contrasts already in toddlers, this study explores whether articulatory and acoustic parameters may likewise differentiate the latent semantics of action verbs. Selecting 3 × 20 emotion-, face-, and hand-related verbs known to activate premotor areas in the brain, their mutual cosine similarities were computed using latent semantic analysis LSA, and the resulting adjacency matrices were compared based on two different large scale text corpora: HAWIK and TASA. Applying hierarchical clustering to identify common structures across the two text corpora, the verbs largely divide into combined mouth and hand movements versus emotional expressions. Transforming the verbs into their constituent phonemes, and projecting them into an articulatory space framed by tongue height and formant frequencies, the clustered small and large size movements appear differentiated by front versus back vowels corresponding to increasing levels of arousal. Whereas the clustered emotional verbs seem characterized by sequences of close versus open jaw produced phonemes, generating up- or downwards shifts in formant frequencies that may influence their perceived valence. Suggesting, that the latent semantics of action verbs reflect parameters of intensity and emotional polarity that appear correlated with the articulatory contrasts and acoustic characteristics of phonemes. PMID:25849977

  5. Latent semantics of action verbs reflect phonetic parameters of intensity and emotional content.

    Science.gov (United States)

    Petersen, Michael Kai

    2015-01-01

    Conjuring up our thoughts, language reflects statistical patterns of word co-occurrences which in turn come to describe how we perceive the world. Whether counting how frequently nouns and verbs combine in Google search queries, or extracting eigenvectors from term document matrices made up of Wikipedia lines and Shakespeare plots, the resulting latent semantics capture not only the associative links which form concepts, but also spatial dimensions embedded within the surface structure of language. As both the shape and movements of objects have been found to be associated with phonetic contrasts already in toddlers, this study explores whether articulatory and acoustic parameters may likewise differentiate the latent semantics of action verbs. Selecting 3 × 20 emotion-, face-, and hand-related verbs known to activate premotor areas in the brain, their mutual cosine similarities were computed using latent semantic analysis LSA, and the resulting adjacency matrices were compared based on two different large scale text corpora: HAWIK and TASA. Applying hierarchical clustering to identify common structures across the two text corpora, the verbs largely divide into combined mouth and hand movements versus emotional expressions. Transforming the verbs into their constituent phonemes, and projecting them into an articulatory space framed by tongue height and formant frequencies, the clustered small and large size movements appear differentiated by front versus back vowels corresponding to increasing levels of arousal. Whereas the clustered emotional verbs seem characterized by sequences of close versus open jaw produced phonemes, generating up- or downwards shifts in formant frequencies that may influence their perceived valence. Suggesting, that the latent semantics of action verbs reflect parameters of intensity and emotional polarity that appear correlated with the articulatory contrasts and acoustic characteristics of phonemes.

  6. Latent semantics of action verbs reflect phonetic parameters of intensity and emotional content.

    Directory of Open Access Journals (Sweden)

    Michael Kai Petersen

    Full Text Available Conjuring up our thoughts, language reflects statistical patterns of word co-occurrences which in turn come to describe how we perceive the world. Whether counting how frequently nouns and verbs combine in Google search queries, or extracting eigenvectors from term document matrices made up of Wikipedia lines and Shakespeare plots, the resulting latent semantics capture not only the associative links which form concepts, but also spatial dimensions embedded within the surface structure of language. As both the shape and movements of objects have been found to be associated with phonetic contrasts already in toddlers, this study explores whether articulatory and acoustic parameters may likewise differentiate the latent semantics of action verbs. Selecting 3 × 20 emotion-, face-, and hand-related verbs known to activate premotor areas in the brain, their mutual cosine similarities were computed using latent semantic analysis LSA, and the resulting adjacency matrices were compared based on two different large scale text corpora: HAWIK and TASA. Applying hierarchical clustering to identify common structures across the two text corpora, the verbs largely divide into combined mouth and hand movements versus emotional expressions. Transforming the verbs into their constituent phonemes, and projecting them into an articulatory space framed by tongue height and formant frequencies, the clustered small and large size movements appear differentiated by front versus back vowels corresponding to increasing levels of arousal. Whereas the clustered emotional verbs seem characterized by sequences of close versus open jaw produced phonemes, generating up- or downwards shifts in formant frequencies that may influence their perceived valence. Suggesting, that the latent semantics of action verbs reflect parameters of intensity and emotional polarity that appear correlated with the articulatory contrasts and acoustic characteristics of phonemes.

  7. The Neutral kaon mixing parameter B(K) from unquenched mixed-action lattice QCD

    Energy Technology Data Exchange (ETDEWEB)

    Christopher Aubin, Jack Laiho, Ruth S. Van de Water

    2010-01-01

    We calculate the neutral kaon mixing parameter B{sub K} in unquenched lattice QCD using asqtad-improved staggered sea quarks and domain-wall valence quarks. We use the '2+1' flavor gauge configurations generated by the MILC Collaboration, and simulate with multiple valence and sea quark masses at two lattice spacings of a {approx} 0.12 fm and a {approx} 0.09 fm. We match the lattice determination of B{sub K} to the continuum value using the nonperturbative method of Rome-Southampton, and extrapolate B{sub K} to the continuum and physical quark masses using mixed action chiral perturbation theory. The 'mixed-action' method enables us to control all sources of systematic uncertainty and therefore to precisely determine B{sub K}; we find a value of B{sub K}{sup {ovr MS},NDR} (2 GeV) = 0.527(6)(21), where the first error is statistical and the second is systematic.

  8. Fish oil curtails the human action potential dome in a heterogeneous manner: Implication for arrhythmogenesis

    NARCIS (Netherlands)

    Verkerk, Arie O.; den Ruijter, Hester M.; de Jonge, Nicolaas; Coronel, Ruben

    2009-01-01

    Omega-3 polyunsaturated fatty acids (omega3-PUFAs) from fish oil modulate various ion channels, including the L-type calcium current (I(Ca,L)). As a result, fish oil shortens the cardiac action potential and may cause a loss of the dome of the action potential (AP). Under conditions of increased

  9. Consumer-Related Food Waste: Causes and Potential for Action

    Directory of Open Access Journals (Sweden)

    Jessica Aschemann-Witzel

    2015-05-01

    Full Text Available In the past decade, food waste has received increased attention on both academic and societal levels. As a cause of negative economic, environmental and social effects, food waste is considered to be one of the sustainability issues that needs to be addressed. In developed countries, consumers are one of the biggest sources of food waste. To successfully reduce consumer-related food waste, it is necessary to have a clear understanding of the factors influencing food waste-related consumer perceptions and behaviors. The present paper presents the results of a literature review and expert interviews on factors causing consumer-related food waste in households and supply chains. Results show that consumers’ motivation to avoid food waste, their management skills of food provisioning and food handling and their trade-offs between priorities have an extensive influence on their food waste behaviors. We identify actions that governments, societal stakeholders and retailers can undertake to reduce consumer-related food waste, highlighting that synergistic actions between all parties are most promising. Further research should focus on exploring specific food waste contexts and interactions more in-depth. Experiments and interventions in particular can contribute to a shift from analysis to solutions.

  10. Parametric study of the Noble's action potential model for cardiac Purkinje fibers

    Energy Technology Data Exchange (ETDEWEB)

    Wang, P.K.C. [Department of Electrical Engineering, University of California, Los Angeles, CA 90095-1594 (United States); Kogan, B.Y. [Department of Computer Science, University of California, Los Angeles, CA 90095-1594 (United States)]. E-mail: kogan@cs.ucla.edu

    2007-08-15

    The effect of parameter variation on repolarization processes in the Noble model (Hodjkin-Huxley type) for action potential (AP) generation in Purkinje cells is studied using a combination of computer simulation and nonlinear dynamic system theory including Hopf bifurcation analysis. Both the original Noble model and a simplified Noble model are used in this study. It is shown that these models have similar qualitative dynamic behavior in the presence of parameter variations. In particular, it is demonstrated that both normal and abnormal modes of cell performance can be obtained by varying the potassium and anion conductances. The abnormal mode (cardiac arrest) may play a significant role in disorganizing the electrical activities in the heart muscles. The existence of Hopf bifurcation with respect to variations in the anion conductance and fixed values of potassium conductances is studied in detail. The regions corresponding to spontaneous AP excitation, and various types of cardiac arrest in the ion-conductance parameter space of both full and simplified Noble models with and without external stimuli are mapped out using computer simulation.

  11. Motor evoked potentials and compound muscle action potentials as prognostic tools for neonates with spina bifida.

    Science.gov (United States)

    Cuppen, Inge; Geerdink, Niels; Rotteveel, Jan J; Mullaart, Reinier; Roeleveld, Nel; Pasman, Jaco W

    2013-03-01

    MEPs and CMAPs as prognostic tools for spina bifida. The aim of this prospective study was to determine the prognostic value of neurophysiological investigations compared to clinical neurological examination in infants with spina bifida. Thirty-six neonates born with spina bifida between 2002 and 2007 were evaluated and followed for 2 years. Lumbar motor evoked potentials (MEPs) and compound muscle action potentials (CMAPs) were obtained at the median age of 2 days old before surgical closure of the spinal anomaly. MEPs were recorded from the quadriceps femoris, tibialis anterior, and gastrocnemius muscles and CMAPs from the latter two muscles. Areas under the curve and latencies of the MEPs and CMAPs were measured. Clinical neurological outcome at the age of 2 years was described using Muscle Function Classes (MFCs) and ambulation status. The areas under the curve of MEPs and CMAPs in the legs were associated with lower neonatal levels of motor and sensory impairment. Better muscle function class of the lower limbs at 2 years of age was associated with larger MEP and CMAP areas of the gastrocnemius and tibialis anterior muscles at neonatal age. MEPs and CMAPs of the gastrocnemius and tibialis anterior muscles are of prognostic value for clinical neurological outcome in neonates born with spina bifida. Copyright © 2012 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  12. Triangulation of the monophasic action potential causes flattening of the electrocardiographic T-wave

    DEFF Research Database (Denmark)

    Bhuiyan, Tanveer Ahmed; Graff, Claus; Thomsen, Morten Bækgaard

    2012-01-01

    It has been proposed that triangulation on the cardiac action potential manifests as a broadened, more flat and notched T-wave on the ECG but to what extent such morphology characteristics are indicative of triangulation is more unclear. In this paper, we have analyzed the morphological changes...... of the action potential under the effect of the IKr blocker sertindole and associated these changes to concurrent changes in the morphology of electrocardiographic T-waves in dogs. We show that, under the effect of sertindole, the peak changes in the morphology of action potentials occur at time points similar...... to those observed for the peak changes in T-wave morphology on the ECG. We further show that the association between action potential shape and ECG shape is dose-dependent and most prominent at the time corresponding to phase 3 of the action potential....

  13. Optimisation of ionic models to fit tissue action potentials: application to 3D atrial modelling.

    Science.gov (United States)

    Al Abed, Amr; Guo, Tianruo; Lovell, Nigel H; Dokos, Socrates

    2013-01-01

    A 3D model of atrial electrical activity has been developed with spatially heterogeneous electrophysiological properties. The atrial geometry, reconstructed from the male Visible Human dataset, included gross anatomical features such as the central and peripheral sinoatrial node (SAN), intra-atrial connections, pulmonary veins, inferior and superior vena cava, and the coronary sinus. Membrane potentials of myocytes from spontaneously active or electrically paced in vitro rabbit cardiac tissue preparations were recorded using intracellular glass microelectrodes. Action potentials of central and peripheral SAN, right and left atrial, and pulmonary vein myocytes were each fitted using a generic ionic model having three phenomenological ionic current components: one time-dependent inward, one time-dependent outward, and one leakage current. To bridge the gap between the single-cell ionic models and the gross electrical behaviour of the 3D whole-atrial model, a simplified 2D tissue disc with heterogeneous regions was optimised to arrive at parameters for each cell type under electrotonic load. Parameters were then incorporated into the 3D atrial model, which as a result exhibited a spontaneously active SAN able to rhythmically excite the atria. The tissue-based optimisation of ionic models and the modelling process outlined are generic and applicable to image-based computer reconstruction and simulation of excitable tissue.

  14. Optimisation of Ionic Models to Fit Tissue Action Potentials: Application to 3D Atrial Modelling

    Science.gov (United States)

    Lovell, Nigel H.; Dokos, Socrates

    2013-01-01

    A 3D model of atrial electrical activity has been developed with spatially heterogeneous electrophysiological properties. The atrial geometry, reconstructed from the male Visible Human dataset, included gross anatomical features such as the central and peripheral sinoatrial node (SAN), intra-atrial connections, pulmonary veins, inferior and superior vena cava, and the coronary sinus. Membrane potentials of myocytes from spontaneously active or electrically paced in vitro rabbit cardiac tissue preparations were recorded using intracellular glass microelectrodes. Action potentials of central and peripheral SAN, right and left atrial, and pulmonary vein myocytes were each fitted using a generic ionic model having three phenomenological ionic current components: one time-dependent inward, one time-dependent outward, and one leakage current. To bridge the gap between the single-cell ionic models and the gross electrical behaviour of the 3D whole-atrial model, a simplified 2D tissue disc with heterogeneous regions was optimised to arrive at parameters for each cell type under electrotonic load. Parameters were then incorporated into the 3D atrial model, which as a result exhibited a spontaneously active SAN able to rhythmically excite the atria. The tissue-based optimisation of ionic models and the modelling process outlined are generic and applicable to image-based computer reconstruction and simulation of excitable tissue. PMID:23935704

  15. Optimisation of Ionic Models to Fit Tissue Action Potentials: Application to 3D Atrial Modelling

    Directory of Open Access Journals (Sweden)

    Amr Al Abed

    2013-01-01

    Full Text Available A 3D model of atrial electrical activity has been developed with spatially heterogeneous electrophysiological properties. The atrial geometry, reconstructed from the male Visible Human dataset, included gross anatomical features such as the central and peripheral sinoatrial node (SAN, intra-atrial connections, pulmonary veins, inferior and superior vena cava, and the coronary sinus. Membrane potentials of myocytes from spontaneously active or electrically paced in vitro rabbit cardiac tissue preparations were recorded using intracellular glass microelectrodes. Action potentials of central and peripheral SAN, right and left atrial, and pulmonary vein myocytes were each fitted using a generic ionic model having three phenomenological ionic current components: one time-dependent inward, one time-dependent outward, and one leakage current. To bridge the gap between the single-cell ionic models and the gross electrical behaviour of the 3D whole-atrial model, a simplified 2D tissue disc with heterogeneous regions was optimised to arrive at parameters for each cell type under electrotonic load. Parameters were then incorporated into the 3D atrial model, which as a result exhibited a spontaneously active SAN able to rhythmically excite the atria. The tissue-based optimisation of ionic models and the modelling process outlined are generic and applicable to image-based computer reconstruction and simulation of excitable tissue.

  16. Local field potentials in primate motor cortex encode grasp kinetic parameters.

    Science.gov (United States)

    Milekovic, Tomislav; Truccolo, Wilson; Grün, Sonja; Riehle, Alexa; Brochier, Thomas

    2015-07-01

    Reach and grasp kinematics are known to be encoded in the spiking activity of neuronal ensembles and in local field potentials (LFPs) recorded from primate motor cortex during movement planning and execution. However, little is known, especially in LFPs, about the encoding of kinetic parameters, such as forces exerted on the object during the same actions. We implanted two monkeys with microelectrode arrays in the motor cortical areas MI and PMd to investigate encoding of grasp-related parameters in motor cortical LFPs during planning and execution of reach-and-grasp movements. We identified three components of the LFP that modulated during grasps corresponding to low (0.3-7Hz), intermediate (~10-~40Hz) and high (~80-250Hz) frequency bands. We show that all three components can be used to classify not only grip types but also object loads during planning and execution of a grasping movement. In addition, we demonstrate that all three components recorded during planning or execution can be used to continuously decode finger pressure forces and hand position related to the grasping movement. Low and high frequency components provide similar classification and decoding accuracies, which were substantially higher than those obtained from the intermediate frequency component. Our results demonstrate that intended reach and grasp kinetic parameters are encoded in multiple LFP bands during both movement planning and execution. These findings also suggest that the LFP is a reliable signal for the control of parameters related to object load and applied pressure forces in brain-machine interfaces. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Alteration of neural action potential patterns by axonal stimulation: the importance of stimulus location.

    Science.gov (United States)

    Crago, Patrick E; Makowski, Nathaniel S

    2014-10-01

    Stimulation of peripheral nerves is often superimposed on ongoing motor and sensory activity in the same axons, without a quantitative model of the net action potential train at the axon endpoint. We develop a model of action potential patterns elicited by superimposing constant frequency axonal stimulation on the action potentials arriving from a physiologically activated neural source. The model includes interactions due to collision block, resetting of the neural impulse generator, and the refractory period of the axon at the point of stimulation. Both the mean endpoint firing rate and the probability distribution of the action potential firing periods depend strongly on the relative firing rates of the two sources and the intersite conduction time between them. When the stimulus rate exceeds the neural rate, neural action potentials do not reach the endpoint and the rate of endpoint action potentials is the same as the stimulus rate, regardless of the intersite conduction time. However, when the stimulus rate is less than the neural rate, and the intersite conduction time is short, the two rates partially sum. Increases in stimulus rate produce non-monotonic increases in endpoint rate and continuously increasing block of neurally generated action potentials. Rate summation is reduced and more neural action potentials are blocked as the intersite conduction time increases. At long intersite conduction times, the endpoint rate simplifies to being the maximum of either the neural or the stimulus rate. This study highlights the potential of increasing the endpoint action potential rate and preserving neural information transmission by low rate stimulation with short intersite conduction times. Intersite conduction times can be decreased with proximal stimulation sites for muscles and distal stimulation sites for sensory endings. The model provides a basis for optimizing experiments and designing neuroprosthetic interventions involving motor or sensory stimulation.

  18. Inducing repetitive action potential firing in neurons via synthesized photoresponsive nanoscale cellular prostheses.

    Science.gov (United States)

    Lu, Siyuan; Madhukar, Anupam

    2013-02-01

    Recently we reported an analysis that examined the potential of synthesized photovoltaic functional abiotic nanosystems (PVFANs) to modulate membrane potential and activate action potential firing in neurons. Here we extend the analysis to delineate the requirements on the electronic energy levels and the attendant photophysical properties of the PVFANs to induce repetitive action potential under continuous light, a capability essential for the proposed potential application of PVFANs as retinal cellular prostheses to compensate for loss of photoreceptors. We find that repetitive action potential firing demands two basic characteristics in the electronic response of the PVFANs: an exponential dependence of the PVFAN excited state decay rate on the membrane potential and a three-state system such that, following photon absorption, the electron decay from the excited state to the ground state is via intermediate state(s) whose lifetime is comparable to the refractory time following an action potential. In this study, the potential of synthetic photovoltaic functional abiotic nanosystems (PVFANs) is examined under continuous light to modulate membrane potential and activate action potential firing in neurons with the proposed potential application of PVFANs as retinal cellular prostheses. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Reconstruction of action potential of repolarization in patients with congenital long-QT syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Kandori, Akihiko [Central Research Laboratory, Hitachi, Ltd, 1-280 Higashi-koigakubo, Kokubunji, Tokyo 185-8601 (Japan); Shimizu, Wataru [National Cardiovascular Center, Osaka (Japan); Yokokawa, Miki [National Cardiovascular Center, Osaka (Japan); Kamakura, Shiro [National Cardiovascular Center, Osaka (Japan); Miyatake, Kunio [National Cardiovascular Center, Osaka (Japan); Murakami, Masahiro [Hitachi High-technologies, Ibaraki (Japan); Miyashita, Tsuyoshi [Central Research Laboratory, Hitachi, Ltd, 1-280 Higashi-koigakubo, Kokubunji, Tokyo 185-8601 (Japan); Ogata, Kuniomi [Central Research Laboratory, Hitachi, Ltd, 1-280 Higashi-koigakubo, Kokubunji, Tokyo 185-8601 (Japan); Tsukada, Keiji [Okayama University, Okayama (Japan)

    2004-05-21

    A method for reconstructing an action potential during the repolarization period was developed. This method uses a current distribution-plotted as a current-arrow map (CAM)-calculated using magnetocardiogram (MCG) signals. The current arrows are summarized during the QRS complex period and subtracted during the ST-T wave period in order to reconstruct the action-potential waveform. To ensure the similarity between a real action potential and the reconstructed action potential using CAM, a monophasic action potential (MAP) and an MCG of the same patient with type-I long-QT syndrome were measured. Although the MAP had one notch that was associated with early afterdepolarization (EAD), the reconstructed action potential had two large and small notches. The small notch timing agreed with the occurrence of the EAD in the MAP. On the other hand, the initiation time of an abnormal current distribution coincides with the appearance timing of the first large notch, and its end time coincides with that of the second small notch. These results suggest that a simple reconstruction method using a CAM based on MCG data can provide a similar action-potential waveform to a MAP waveform without having to introduce a catheter.

  20. Effects of tacrolimus on action potential configuration and transmembrane ion currents in canine ventricular cells.

    Science.gov (United States)

    Szabó, László; Szentandrássy, Norbert; Kistamás, Kornél; Hegyi, Bence; Ruzsnavszky, Ferenc; Váczi, Krisztina; Horváth, Balázs; Magyar, János; Bányász, Tamás; Pál, Balázs; Nánási, Péter P

    2013-03-01

    Tacrolimus is a commonly used immunosuppressive agent which causes cardiovascular complications, e.g., hypertension and hypertrophic cardiomyopathy. In spite of it, there is little information on the cellular cardiac effects of the immunosuppressive agent tacrolimus in larger mammals. In the present study, therefore, the concentration-dependent effects of tacrolimus on action potential morphology and the underlying ion currents were studied in canine ventricular cardiomyocytes. Standard microelectrode, conventional whole cell patch clamp, and action potential voltage clamp techniques were applied in myocytes enzymatically dispersed from canine ventricular myocardium. Tacrolimus (3-30 μM) caused a concentration-dependent reduction of maximum velocity of depolarization and repolarization, action potential amplitude, phase-1 repolarization, action potential duration, and plateau potential, while no significant change in the resting membrane potential was observed. Conventional voltage clamp experiments revealed that tacrolimus concentrations ≥3 μM blocked a variety of ion currents, including I(Ca), I(to), I(K1), I(Kr), and I(Ks). Similar results were obtained under action potential voltage clamp conditions. These effects of tacrolimus developed rapidly and were fully reversible upon washout. The blockade of inward currents with the concomitant shortening of action potential duration in canine myocytes is the opposite of those observed previously with tacrolimus in small rodents. It is concluded that although tacrolimus blocks several ion channels at higher concentrations, there is no risk of direct interaction with cardiac ion channels when applying tacrolimus in therapeutic concentrations.

  1. Computer Simulations Support a Morphological Contribution to BDNF Enhancement of Action Potential Generation

    Directory of Open Access Journals (Sweden)

    Domenico F Galati

    2016-09-01

    Full Text Available Abstract Brain-derived neurotrophic factor (BDNF regulates both action potential (AP generation and neuron morphology. However, whether BDNF-induced changes in neuron morphology directly impact AP generation is unclear. We quantified BDNF’s effect on cultured cortical neuron morphological parameters and found that BDNF stimulates dendrite growth and addition of dendrites while increasing both excitatory and inhibitory presynaptic inputs in a spatially restricted manner. To gain insight into how these combined changes in neuron structure and synaptic input impact AP generation, we used the morphological parameters we gathered to generate computational models. Simulations suggest that BDNF-induced neuron morphologies generate more APs under a wide variety of conditions. Synapse and dendrite addition have the greatest impact on AP generation. However, subtle alterations in excitatory/inhibitory synapse ratio and strength have a significant impact on AP generation when synaptic activity is low. Consistent with these simulations, BDNF rapidly enhances spontaneous activity in cortical cultures. We propose that BDNF promotes neuron morphologies that are intrinsically more efficient at translating barrages of synaptic activity into APs, which is a previously unexplored aspect of BDNF’s function.

  2. Sensitivity analysis of potential events affecting the double-shell tank system and fallback actions

    Energy Technology Data Exchange (ETDEWEB)

    Knutson, B.J.

    1996-09-27

    Sensitivity analyses were performed for fall-back positions (i.e., management actions) to accommodate potential off-normal and programmatic change events overlaid on the waste volume projections and their uncertainties. These sensitivity analyses allowed determining and ranking tank system high-risk parameters and fall- back positions that will accommodate the respective impacts. This quantification of tank system impacts shows periods where tank capacity is sensitive to certain variables that must be carefully managed and/or evaluated. Identifying these sensitive variables and quantifying their impact will allow decision makers to prepare fall-back positions and focus available resources on the highest impact parameters where technical data are needed to reduce waste projection uncertainties. For noncomplexed waste, the period of capacity vulnerability occurs during the years of single-shell tank (SST) retrieval (after approximately 2009) due to the sensitivity to several variables. Ranked by importance these variables include the pretreatment rate and 200-East SST solids transfer volume. For complexed waste, the period of capacity vulnerability occurs during the period after approximately 2005 due to the sensitivity to several variables. Ranked by importance these variables include the pretreatment rate. 200-East SST solids transfer volume. complexed waste reduction factor using evaporation, and 200-west saltwell liquid porosity.

  3. Motor unit action potential conduction velocity estimated from surface electromyographic signals using image processing techniques.

    Science.gov (United States)

    Soares, Fabiano Araujo; Carvalho, João Luiz Azevedo; Miosso, Cristiano Jacques; de Andrade, Marcelino Monteiro; da Rocha, Adson Ferreira

    2015-09-17

    In surface electromyography (surface EMG, or S-EMG), conduction velocity (CV) refers to the velocity at which the motor unit action potentials (MUAPs) propagate along the muscle fibers, during contractions. The CV is related to the type and diameter of the muscle fibers, ion concentration, pH, and firing rate of the motor units (MUs). The CV can be used in the evaluation of contractile properties of MUs, and of muscle fatigue. The most popular methods for CV estimation are those based on maximum likelihood estimation (MLE). This work proposes an algorithm for estimating CV from S-EMG signals, using digital image processing techniques. The proposed approach is demonstrated and evaluated, using both simulated and experimentally-acquired multichannel S-EMG signals. We show that the proposed algorithm is as precise and accurate as the MLE method in typical conditions of noise and CV. The proposed method is not susceptible to errors associated with MUAP propagation direction or inadequate initialization parameters, which are common with the MLE algorithm. Image processing -based approaches may be useful in S-EMG analysis to extract different physiological parameters from multichannel S-EMG signals. Other new methods based on image processing could also be developed to help solving other tasks in EMG analysis, such as estimation of the CV for individual MUs, localization and tracking of innervation zones, and study of MU recruitment strategies.

  4. State and location dependence of action potential metabolic cost in cortical pyramidal neurons

    NARCIS (Netherlands)

    Hallermann, Stefan; de Kock, Christiaan P. J.; Stuart, Greg J.; Kole, Maarten H. P.

    2012-01-01

    Action potential generation and conduction requires large quantities of energy to restore Na+ and K+ ion gradients. We investigated the subcellular location and voltage dependence of this metabolic cost in rat neocortical pyramidal neurons. Using Na+/K+ charge overlap as a measure of action

  5. State and location dependence of action potential metabolic cost in cortical pyramidal neurons

    NARCIS (Netherlands)

    Hallermann, S.; de Kock, C.P.J.; Stuart, G.J.; Kole, M.H.

    2012-01-01

    Action potential generation and conduction requires large quantities of energy to restore Na + and K + ion gradients. We investigated the subcellular location and voltage dependence of this metabolic cost in rat neocortical pyramidal neurons. Using Na +K + charge overlap as a measure of action

  6. Consequences of converting graded to action potentials upon neural information coding and energy efficiency.

    Directory of Open Access Journals (Sweden)

    Biswa Sengupta

    2014-01-01

    Full Text Available Information is encoded in neural circuits using both graded and action potentials, converting between them within single neurons and successive processing layers. This conversion is accompanied by information loss and a drop in energy efficiency. We investigate the biophysical causes of this loss of information and efficiency by comparing spiking neuron models, containing stochastic voltage-gated Na(+ and K(+ channels, with generator potential and graded potential models lacking voltage-gated Na(+ channels. We identify three causes of information loss in the generator potential that are the by-product of action potential generation: (1 the voltage-gated Na(+ channels necessary for action potential generation increase intrinsic noise and (2 introduce non-linearities, and (3 the finite duration of the action potential creates a 'footprint' in the generator potential that obscures incoming signals. These three processes reduce information rates by ∼50% in generator potentials, to ∼3 times that of spike trains. Both generator potentials and graded potentials consume almost an order of magnitude less energy per second than spike trains. Because of the lower information rates of generator potentials they are substantially less energy efficient than graded potentials. However, both are an order of magnitude more efficient than spike trains due to the higher energy costs and low information content of spikes, emphasizing that there is a two-fold cost of converting analogue to digital; information loss and cost inflation.

  7. Selective activation of heteromeric SK channels contributes to action potential repolarization in mouse atrial myocytes.

    Science.gov (United States)

    Hancock, Jane M; Weatherall, Kate L; Choisy, Stéphanie C; James, Andrew F; Hancox, Jules C; Marrion, Neil V

    2015-05-01

    Activation of small conductance calcium-activated potassium (SK) channels is proposed to contribute to repolarization of the action potential in atrial myocytes. This role is controversial, as these cardiac SK channels appear to exhibit an uncharacteristic pharmacology. The objectives of this study were to resolve whether activation of SK channels contributes to atrial action potential repolarization and to determine the likely subunit composition of the channel. The effect of 2 SK channel inhibitors was assessed on outward current evoked in voltage clamp and on action potential duration in perforated patch and whole-cell current clamp recording from acutely isolated mouse atrial myocytes. The presence of SK channel subunits was assessed using immunocytochemistry. A significant component of outward current was reduced by the SK channel blockers apamin and UCL1684. Block by apamin displayed a sensitivity indicating that this current was carried by homomeric SK2 channels. Action potential duration was significantly prolonged by UCL1684, but not by apamin. This effect was accompanied by an increase in beat-to-beat variability and action potential triangulation. This pharmacology was matched by that of expressed heteromeric SK2-SK3 channels in HEK293 cells. Immunocytochemistry showed that atrial myocytes express both SK2 and SK3 channels with an overlapping expression pattern. Only proposed heteromeric SK2-SK3 channels are physiologically activated to contribute to action potential repolarization, which is indicated by the difference in pharmacology of evoked outward current and prolongation of atrial action potential duration. The effect of blocking this channel on the action potential suggests that SK channel inhibition during cardiac function has the potential to be proarrhythmic. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  8. Differential roles of two delayed rectifier potassium currents in regulation of ventricular action potential duration and arrhythmia susceptibility.

    Science.gov (United States)

    Devenyi, Ryan A; Ortega, Francis A; Groenendaal, Willemijn; Krogh-Madsen, Trine; Christini, David J; Sobie, Eric A

    2017-04-01

    Arrhythmias result from disruptions to cardiac electrical activity, although the factors that control cellular action potentials are incompletely understood. We combined mathematical modelling with experiments in heart cells from guinea pigs to determine how cellular electrical activity is regulated. A mismatch between modelling predictions and the experimental results allowed us to construct an improved, more predictive mathematical model. The balance between two particular potassium currents dictates how heart cells respond to perturbations and their susceptibility to arrhythmias. Imbalances of ionic currents can destabilize the cardiac action potential and potentially trigger lethal cardiac arrhythmias. In the present study, we combined mathematical modelling with information-rich dynamic clamp experiments to determine the regulation of action potential morphology in guinea pig ventricular myocytes. Parameter sensitivity analysis was used to predict how changes in ionic currents alter action potential duration, and these were tested experimentally using dynamic clamp, a technique that allows for multiple perturbations to be tested in each cell. Surprisingly, we found that a leading mathematical model, developed with traditional approaches, systematically underestimated experimental responses to dynamic clamp perturbations. We then re-parameterized the model using a genetic algorithm, which allowed us to estimate ionic current levels in each of the cells studied. This unbiased model adjustment consistently predicted an increase in the rapid delayed rectifier K + current and a drastic decrease in the slow delayed rectifier K + current, and this prediction was validated experimentally. Subsequent simulations with the adjusted model generated the clinically relevant prediction that the slow delayed rectifier is better able to stabilize the action potential and suppress pro-arrhythmic events than the rapid delayed rectifier. In summary, iterative coupling of

  9. Altered Chloride Homeostasis Decreases the Action Potential Threshold and Increases Hyperexcitability in Hippocampal Neurons

    DEFF Research Database (Denmark)

    Sørensen, Andreas T; Ledri, Marco; Melis, Miriam

    2017-01-01

    flows through activated GABAA receptors into the neurons causing hyperpolarization or shunting inhibition, and in turn inhibits action potential (AP) generation. However, in situations when intracellular chloride concentration is increased, chloride ions can flow in opposite direction, depolarize...

  10. Optical coherence tomography for compound action potential detection: a computational study

    Science.gov (United States)

    Troiani, Francesca; Nikolic, Konstantin; Constandinou, Timothy G.

    2017-07-01

    The feasibility of using time domain optical coherence tomography (TD-OCT) to detect compound action potential in a peripheral nerve and the setup characteristics, are studied through the use of finite-difference time-domain (FDTD) technique.

  11. Spatial and frequency domain ring source models for the single muscle fiber action potential

    DEFF Research Database (Denmark)

    Henneberg, Kaj-åge; R., Plonsey

    1994-01-01

    In the paper, single-fibre models for the extracellular action potential are developed that will allow the potential to the evaluated at an arbitrary field point in the extracellular space. Fourier-domain models are restricted in that they evaluate potentials at equidistant points along a line...

  12. 7 CFR 1945.19 - Reporting potential natural disasters and initial actions.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 13 2010-01-01 2009-01-01 true Reporting potential natural disasters and initial... Assistance-General § 1945.19 Reporting potential natural disasters and initial actions. (a) Purpose. The purpose of reporting potential natural disasters is to provide a systematic procedure for rapid reporting...

  13. Distinct electrophysiological potentials for intention in action and prior intention for action.

    Science.gov (United States)

    Vinding, Mikkel C; Jensen, Mads; Overgaard, Morten

    2014-01-01

    The role of conscious intention in relation to motoric movements has become a major topic of investigation in neuroscience. Traditionally, reports of conscious intention have been compared to various features of the readiness-potential (RP)--an electrophysiological signal that appears before voluntary movements. Experiments, however, tend to study intentions in immediate relation to movements (proximal intentions), thus ignoring other aspects of intentions such as planning or deciding in advance of movement (distal intentions). The current study examines the difference in electrophysiological activity between proximal intention and distal intention, using electroencephalography (EEG). Participants had to form an intention to move and then wait 2.5 sec before performing the actual movement. In this way, the electrophysiological activity related to forming a conscious intention was separated from any confounding activity related to automated motor activity. This was compared to conditions in which participants had to act as soon as they had the intention and a condition where participants acted upon an external cue 2.5 sec prior to movement. We examined the RP for the three conditions. No difference was found in early RP, but late RP differed significantly depending on the type of intention. In addition, we analysed signals during a longer time-interval starting before the time of distal intention formation until after the actual movement concluded. Results showed a slow negative electrophysiological "intention potential" above the mid-frontal areas at the time participants formed a distal intention. This potential was only found when the distal intention was self-paced and not when the intention was formed in response to an external cue. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Action potential bursts in central snail neurons elicited by procaine: roles of ionic currents.

    Science.gov (United States)

    Lin, Chia-Hsien; Lin, Pei-Lin; Tsai, Ming-Cheng; Hsu, Hui-Yu; Yang, Han-Yin; Chuang, Chieh-Min; Chen, Yi-Hung

    2010-10-31

    The role of ionic currents on procaine-elicited action potential bursts was studied in an identifiable RP1 neuron of the African snail, Achatina fulica Ferussac, using the two-electrode voltage clamp method. The RP1 neuron generated spontaneous action potentials and bath application of procaine at 10 mM reversibly elicited action potential bursts in a concentration-dependent manner. Voltage clamp studies revealed that procaine at 10 mM decreased [1] the Ca2+ current, [2] the Na+ current, [3] the delayed rectifying K+ current I(KD), and [4] the fast-inactivating K+ current (I(A)). Action potential bursts were not elicited by 4-aminopyridine (4-AP), an inhibitor of I(A), whereas they were seen after application of tetraethylammonium chloride (TEA), a blocker of the I(K)(Ca) and I(KD) currents, and tacrine, an inhibitor of I(KD). Pretreatment with U73122, a phospholipase C inhibitor, blocked the action potential bursts elicited by procaine. U73122 did not affect the I(KD) of the RP1 neuron; however, U73122 decreased the inhibitory effect of procaine on the I(KD). Tacrine decreased the TEA-sensitive I(KD) of RP1 neuron but did not significantly affect the I(A). Tacrine also successfully induced action potential bursts in the RP1 neuron. It is concluded that the inhibition on the I(KD) is responsible for the generation of action potential bursts in the central snail RP1 neuron. Further, phospholipase C activity is involved in the procaine-elicited I(KD) inhibition and action potential bursts.

  15. Dynamic properties of the action potential encoder in an insect mechanosensory neuron.

    OpenAIRE

    French, A.S.

    1984-01-01

    A variety of sensory receptors show adaptation to dynamic stimuli that can be well characterized as fractional differentiation of the input signal. The cause of this behavior is unknown, but because it can be represented by linear systems theory, it has been assumed to arise during early linear processes of transduction or adaptation, rather than during the nonlinear process of action potential encoding. I measured the action potential encoding properties of an insect mechanoreceptor by direc...

  16. Distinct electrophysiological potentials for intention in action and prior intention for action

    DEFF Research Database (Denmark)

    Vinding, Mikkel C; Jensen, Mads; Overgaard, Morten

    2014-01-01

    The role of conscious intention in relation to motoric movements has become a major topic of investigation in neuroscience. Traditionally, reports of conscious intention have been compared to various features of the readiness-potential (RP) – an electrophysiological signal that appears before...... voluntary movements. Experiments, however, tend to study intentions in immediate relation to movements (proximal intentions), thus ignoring other aspects of intentions such as planning or deciding in advance of movement (distal intentions). The current study examines the difference in electrophysiological...... activity between proximal intention and distal intention, using electroencephalography (EEG). Participants had to form an intention to move and then wait 2.5 sec before performing the actual movement. In this way, the electrophysiological activity related to forming a conscious intention was separated from...

  17. Detection of Variability of the Motor Unit Action Potential Shape by Means of the Firing Patterns

    DEFF Research Database (Denmark)

    Krarup, Christian; Nikolic, Mile; Dahl, Kristian

    1997-01-01

    The motor unit action potential is a summation of the potentials of the individual muscle fibers from the same motor unit.By using a newly developed automatic EMG decomposition system, variability of the firing patterns of the muscle fibers are analyzed.......The motor unit action potential is a summation of the potentials of the individual muscle fibers from the same motor unit.By using a newly developed automatic EMG decomposition system, variability of the firing patterns of the muscle fibers are analyzed....

  18. Action Monitoring in Children with or without a Family History of ADHD--Effects of Gender on an Endophenotype Parameter

    Science.gov (United States)

    Albrecht, Bjorn; Brandeis, Daniel; Uebel, Henrik; Heinrich, Hartmut; Heise, Alexander; Hasselhorn, Marcus; Rothenberger, Aribert; Banaschewski, Tobias

    2010-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is a frequent and highly heritable disorder overrepresented in boys. In a recent study investigating boys only, we found that action monitoring deficits as reflected by certain behavioral and electrophysiological parameters were familially driven. As gender may also have an important impact, this was…

  19. Minocycline inhibits D-amphetamine-elicited action potential bursts in a central snail neuron.

    Science.gov (United States)

    Chen, Y-H; Lin, P-L; Wong, R-W; Wu, Y-T; Hsu, H-Y; Tsai, M-C; Lin, M-J; Hsu, Y-C; Lin, C-H

    2012-10-25

    Minocycline is a second-generation tetracycline that has been reported to have powerful neuroprotective properties. In our previous studies, we found that d-amphetamine (AMPH) elicited action potential bursts in an identifiable RP4 neuron of the African snail, Achatina fulica Ferussac. This study sought to determine the effects of minocycline on the AMPH-elicited action potential pattern changes in the central snail neuron, using the two-electrode voltage clamping method. Extracellular application of AMPH at 300 μM elicited action potential bursts in the RP4 neuron. Minocycline dose-dependently (300-900 μM) inhibited the action potential bursts elicited by AMPH. The inhibitory effects of minocycline on AMPH-elicited action potential bursts were restored by forskolin (50 μM), an adenylate cyclase activator, and by dibutyryl cAMP (N(6),2'-O-Dibutyryladenosine 3',5'-cyclic monophosphate; 1mM), a membrane-permeable cAMP analog. Co-administration of forskolin (50 μM) plus tetraethylammonium chloride (TEA; 5mM) or co-administration of TEA (5mM) plus dibutyryl cAMP (1mM) also elicited action potential bursts, which were prevented and inhibited by minocycline. In addition, minocycline prevented and inhibited forskolin (100 μM)-elicited action potential bursts. Notably, TEA (50mM)-elicited action potential bursts in the RP4 neuron were not affected by minocycline. Minocycline did not affect steady-state outward currents of the RP4 neuron. However, minocycline did decrease the AMPH-elicited steady-state current changes. Similarly, minocycline decreased the effects of forskolin-elicited steady-state current changes. Pretreatment with H89 (N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride; 10 μM), a protein kinase A inhibitor, inhibited AMPH-elicited action potential bursts and decreased AMPH-elicited steady-state current changes. These results suggest that the cAMP-protein kinase A signaling pathway and the steady-state current are involved in

  20. Increased event-related potentials and alpha-, beta- and gamma-activity associated with intentional actions

    Directory of Open Access Journals (Sweden)

    Susanne eKarch

    2016-01-01

    Full Text Available Objective: Internally guided actions are defined as being purposeful, self-generated and offering choices between alternatives. Intentional actions are essential to reach individual goals. In previous empirical studies, internally guided actions were predominantly related to functional responses in frontal and parietal areas. The aim of the present study was to distinguish event-related potentials and oscillatory responses of intentional actions and externally guided actions. In addition, we compared neurobiological findings of the decision which action to perform with those referring to the decision whether or not to perform an action. Methods: Twenty-eight subjects participated in adapted go/nogo paradigms, including a voluntary selection condition allowing participants to [1] freely decide whether to press the response button or [2] to decide whether they wanted to press the response button with the right index finger or the left index finger. Results: The reaction times were increased when participants freely decided whether and how they wanted to respond compared to the go condition. Intentional processes were associated with a fronto-centrally located N2 and P3 potential. N2 and P3 amplitudes were increased during intentional actions compared to instructed responses (go. In addition, increased activity in the alpha-, beta- and gamma-frequency range was shown during voluntary behaviour rather than during externally-guided responses. Conclusion: These results may indicate that an additional cognitive process is needed for intentional actions compared to instructed behaviour. However, the neural responses were comparatively independent of the kind of decision that was made (1. decision which action to perform; 2. decision whether or not to perform an action. Significance: The study demonstrates the importance of fronto-central alpha-, beta- and gamma oscillations for voluntary behaviour.

  1. Human ex-vivo action potential model for pro-arrhythmia risk assessment.

    Science.gov (United States)

    Page, Guy; Ratchada, Phachareeya; Miron, Yannick; Steiner, Guido; Ghetti, Andre; Miller, Paul E; Reynolds, Jack A; Wang, Ken; Greiter-Wilke, Andrea; Polonchuk, Liudmila; Traebert, Martin; Gintant, Gary A; Abi-Gerges, Najah

    2016-01-01

    While current S7B/E14 guidelines have succeeded in protecting patients from QT-prolonging drugs, the absence of a predictive paradigm identifying pro-arrhythmic risks has limited the development of valuable drug programs. We investigated if a human ex-vivo action potential (AP)-based model could provide a more predictive approach for assessing pro-arrhythmic risk in man. Human ventricular trabeculae from ethically consented organ donors were used to evaluate the effects of dofetilide, d,l-sotalol, quinidine, paracetamol and verapamil on AP duration (APD) and recognized pro-arrhythmia predictors (short-term variability of APD at 90% repolarization (STV(APD90)), triangulation (ADP90-APD30) and incidence of early afterdepolarizations at 1 and 2Hz to quantitatively identify the pro-arrhythmic risk. Each drug was blinded and tested separately with 3 concentrations in triplicate trabeculae from 5 hearts, with one vehicle time control per heart. Electrophysiological stability of the model was not affected by sequential applications of vehicle (0.1% dimethyl sulfoxide). Paracetamol and verapamil did not significantly alter anyone of the AP parameters and were classified as devoid of pro-arrhythmic risk. Dofetilide, d,l-sotalol and quinidine exhibited an increase in the manifestation of pro-arrhythmia markers. The model provided quantitative and actionable activity flags and the relatively low total variability in tissue response allowed for the identification of pro-arrhythmic signals. Power analysis indicated that a total of 6 trabeculae derived from 2 hearts are sufficient to identify drug-induced pro-arrhythmia. Thus, the human ex-vivo AP-based model provides an integrative translational assay assisting in shaping clinical development plans that could be used in conjunction with the new CiPA-proposed approach. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Active action potential propagation but not initiation in thalamic interneuron dendrites

    Science.gov (United States)

    Casale, Amanda E.; McCormick, David A.

    2012-01-01

    Inhibitory interneurons of the dorsal lateral geniculate nucleus of the thalamus modulate the activity of thalamocortical cells in response to excitatory input through the release of inhibitory neurotransmitter from both axons and dendrites. The exact mechanisms by which release can occur from dendrites are, however, not well understood. Recent experiments using calcium imaging have suggested that Na/K based action potentials can evoke calcium transients in dendrites via local active conductances, making the back-propagating action potential a candidate for dendritic neurotransmitter release. In this study, we employed high temporal and spatial resolution voltage-sensitive dye imaging to assess the characteristics of dendritic voltage deflections in response to Na/K action potentials in interneurons of the mouse dorsal lateral geniculate nucleus. We found that trains or single action potentials elicited by somatic current injection or local synaptic stimulation led to action potentials that rapidly and actively back-propagated throughout the entire dendritic arbor and into the fine filiform dendritic appendages known to release GABAergic vesicles. Action potentials always appeared first in the soma or proximal dendrite in response to somatic current injection or local synaptic stimulation, and the rapid back-propagation into the dendritic arbor depended upon voltage-gated sodium and TEA-sensitive potassium channels. Our results indicate that thalamic interneuron dendrites integrate synaptic inputs that initiate action potentials, most likely in the axon initial segment, that then back-propagate with high-fidelity into the dendrites, resulting in a nearly synchronous release of GABA from both axonal and dendritic compartments. PMID:22171033

  3. Effect of an educational game on university students' learning about action potentials.

    Science.gov (United States)

    Luchi, Kelly Cristina Gaviao; Montrezor, Luís Henrique; Marcondes, Fernanda K

    2017-06-01

    The aim of this study was to evaluate the effect of an educational game that is used for teaching the mechanisms of the action potentials in cell membranes. The game was composed of pieces representing the intracellular and extracellular environments, ions, ion channels, and the Na+-K+-ATPase pump. During the game activity, the students arranged the pieces to demonstrate how the ions move through the membrane in a resting state and during an action potential, linking the ion movement with a graph of the action potential. To test the effect of the game activity on student understanding, first-year dental students were given the game to play at different times in a series of classes teaching resting membrane potential and action potentials. In all experiments, students who played the game performed better in assessments. According to 98% of the students, the game supported the learning process. The data confirm the students' perception, indicating that the educational game improved their understanding about action potentials. Copyright © 2017 the American Physiological Society.

  4. Two types of action potential configuration in single cardiac Purkinje cells of sheep

    NARCIS (Netherlands)

    Verkerk, A. O.; Veldkamp, M. W.; Abbate, F.; Antoons, G.; Bouman, L. N.; Ravesloot, J. H.; van Ginneken, A. C.

    1999-01-01

    Membrane potentials and currents of isolated sheep Purkinje and ventricular cells were compared using patch-clamp and microelectrode techniques. In approximately 50% of Purkinje cells, we observed action potentials that showed a prominent phase 1 repolarization and relatively negative plateau (LP

  5. Perturbation analysis of spontaneous action potential initiation by stochastic ion channels

    KAUST Repository

    Keener, James P.

    2011-07-01

    A stochastic interpretation of spontaneous action potential initiation is developed for the Morris-Lecar equations. Initiation of a spontaneous action potential can be interpreted as the escape from one of the wells of a double well potential, and we develop an asymptotic approximation of the mean exit time using a recently developed quasistationary perturbation method. Using the fact that the activating ionic channel\\'s random openings and closings are fast relative to other processes, we derive an accurate estimate for the mean time to fire an action potential (MFT), which is valid for a below-threshold applied current. Previous studies have found that for above-threshold applied current, where there is only a single stable fixed point, a diffusion approximation can be used. We also explore why different diffusion approximation techniques fail to estimate the MFT. © 2011 American Physical Society.

  6. [Effect of pulse magnetic field on distribution of neuronal action potential].

    Science.gov (United States)

    Zheng, Yu; Cai, Di; Wang, Jin-Hai; Li, Gang; Lin, Ling

    2014-08-25

    The biological effect on the organism generated by magnetic field is widely studied. The present study was aimed to observe the change of sodium channel under magnetic field in neurons. Cortical neurons of Kunming mice were isolated, subjected to 15 Hz, 1 mT pulse magnetic stimulation, and then the currents of neurons were recorded by whole-cell patch clamp. The results showed that, under magnetic stimulation, the activation process of Na(+) channel was delayed, and the inactivation process was accelerated. Given the classic three-layer model, the polarization diagram of cell membrane potential distribution under pulse magnetic field was simulated, and it was found that the membrane potential induced was associated with the frequency and intensity of magnetic field. Also the effect of magnetic field-induced current on action potential was simulated by Hodgkin-Huxley (H-H) model. The result showed that the generation of action potential was delayed, and frequency and the amplitudes were decreased when working current was between -1.32 μA and 0 μA. When the working current was higher than 0 μA, the generation frequency of action potential was increased, and the change of amplitudes was not obvious, and when the working current was lower than -1.32 μA, the time of rising edge and amplitudes of action potential were decreased drastically, and the action potential was unable to generate. These results suggest that the magnetic field simulation can affect the distribution frequency and amplitude of action potential of neuron via sodium channel mediation.

  7. Prolonged action potential duration in cardiac ablation of PDK1 mice.

    Science.gov (United States)

    Han, Zhonglin; Jiang, Yu; Yang, Zhongzhou; Cao, Kejiang; Wang, Dao W

    2015-01-01

    The involvement of the AGC protein kinase family in regulating arrhythmia has drawn considerable attention, but the underlying mechanisms are still not clear. The aim of this study is to explore the role of 3-phosphoinositide-dependent protein kinase-1 (PDK1), one of upstream protein kinases of the AGC protein kinase family, in the pathogenesis of dysregulated electrophysiological basis. PDK1(F/F) αMHC-Cre mice and PDK1(F/F) mice were divided into experiment group and control group. Using patch clamping technology, we explored action potential duration in both groups, and investigated the functions of transient outward potassium channel and L-type Ca(2+) channel to explain the abnormal action potential duration. Significant prolongation action potential duration was found in mice with PDK1 deletion. Further, the peak current of transient outward potassium current and L-type Ca(2+) current were decreased by 84% and 49% respectively. In addition, dysregulation of channel kinetics lead to action potential duration prolongation further. In conclusion, we have demonstrated that PDK1 participates in action potential prolongation in cardiac ablation of PDK1 mice. This effect is likely to be mediated largely through downregulation of transient outward potassium current. These findings indicate the modulation of the PDK1 pathway could provide a new mechanism for abnormal electrophysiological basis.

  8. Shifted one-parameter supersymmetric family of quartic asymmetric double-well potentials

    Energy Technology Data Exchange (ETDEWEB)

    Rosu, Haret C., E-mail: hcr@ipicyt.edu.mx [IPICYT, Instituto Potosino de Investigacion Cientifica y Tecnologica, Camino a la presa San José 2055, Col. Lomas 4a Sección, 78216 San Luis Potosí, S.L.P. (Mexico); Mancas, Stefan C., E-mail: mancass@erau.edu [Department of Mathematics, Embry-Riddle Aeronautical University, Daytona Beach, FL 32114-3900 (United States); Chen, Pisin, E-mail: pisinchen@phys.ntu.edu.tw [Leung Center for Cosmology and Particle Astrophysics (LeCosPA) and Department of Physics, National Taiwan University, Taipei 10617, Taiwan (China)

    2014-10-15

    Extending our previous work (Rosu, 2014), we define supersymmetric partner potentials through a particular Riccati solution of the form F(x)=(x−c){sup 2}−1, where c is a real shift parameter, and work out the quartic double-well family of one-parameter isospectral potentials obtained by using the corresponding general Riccati solution. For these parametric double well potentials, we study how the localization properties of the two wells depend on the parameter of the potentials for various values of the shifting parameter. We also consider the supersymmetric parametric family of the first double-well potential in the Razavy chain of double well potentials corresponding to F(x)=1/2 sinh2x−2((1+√(2))sinh2x)/((1+√(2))cosh2x+1) , both unshifted and shifted, to test and compare the localization properties. - Highlights: • Quartic one-parameter DWs with an additional shift parameter are introduced. • Anomalous localization feature of their zero modes is confirmed at different shifts. • Razavy one-parameter DWs are also introduced and shown not to have this feature.

  9. Averaged Solvent Embedding Potential Parameters for Multiscale Modeling of Molecular Properties

    DEFF Research Database (Denmark)

    Beerepoot, Maarten; Steindal, Arnfinn Hykkerud; List, Nanna Holmgaard

    2016-01-01

    We derive and validate averaged solvent parameters for embedding potentials to be used in polarizable embedding quantum mechanics/molecular mechanics (QM/MM) molecular property calculations of solutes in organic solvents. The parameters are solvent-specific atom-centered partial charges...... by analyzing the quality of the resulting molecular electrostatic potentials with respect to full QM potentials. We show that a combination of geometry-specific parameters for solvent molecules close to the QM region and averaged parameters for solvent molecules further away allows for efficient polarizable...... embedding multiscale modeling without compromising the accuracy. The results are promising for the development of general embedding parameters for biomolecules, where the reduction in computational cost can be considerable....

  10. Photodynamic action of chlorin e6 on thymocyte plasmatic and mitochondrial membrane potentials

    Science.gov (United States)

    Gyulkhandanyan, Grigor V.

    2005-08-01

    Transmembrane potentials appear to be cell state sensitive characteristics and can give information about cell damage initial stage. Photodynamic action of the photosensitizer chlorin e6 on plasmatic and mitochondrial membrane potentials of the rat thymus lymphocytes was studied using voltage-sensitive dye rhodamine 6G. It has been revealed that mitochondrial membrane potential is more sensitive characteristic of membrane disfunction than plasmatic one at the cell photodamage.

  11. Nonlinear diffusion and thermo-electric coupling in a two-variable model of cardiac action potential

    Science.gov (United States)

    Gizzi, A.; Loppini, A.; Ruiz-Baier, R.; Ippolito, A.; Camassa, A.; La Camera, A.; Emmi, E.; Di Perna, L.; Garofalo, V.; Cherubini, C.; Filippi, S.

    2017-09-01

    This work reports the results of the theoretical investigation of nonlinear dynamics and spiral wave breakup in a generalized two-variable model of cardiac action potential accounting for thermo-electric coupling and diffusion nonlinearities. As customary in excitable media, the common Q10 and Moore factors are used to describe thermo-electric feedback in a 10° range. Motivated by the porous nature of the cardiac tissue, in this study we also propose a nonlinear Fickian flux formulated by Taylor expanding the voltage dependent diffusion coefficient up to quadratic terms. A fine tuning of the diffusive parameters is performed a priori to match the conduction velocity of the equivalent cable model. The resulting combined effects are then studied by numerically simulating different stimulation protocols on a one-dimensional cable. Model features are compared in terms of action potential morphology, restitution curves, frequency spectra, and spatio-temporal phase differences. Two-dimensional long-run simulations are finally performed to characterize spiral breakup during sustained fibrillation at different thermal states. Temperature and nonlinear diffusion effects are found to impact the repolarization phase of the action potential wave with non-monotone patterns and to increase the propensity of arrhythmogenesis.

  12. Optical magnetic detection of single-neuron action potentials using NV-diamond

    Science.gov (United States)

    Turner, Matthew; Barry, John; Schloss, Jennifer; Glenn, David; Walsworth, Ron

    2016-05-01

    A key challenge for neuroscience is noninvasive, label-free sensing of action potential dynamics in whole organisms with single-neuron resolution. Here, we report a new approach to this problem: using nitrogen-vacancy (NV) color centers in diamond to measure the time-dependent magnetic fields produced by single-neuron action potentials. We demonstrate our method using excised single neurons from two invertebrate species, marine worm and squid; and then by single-neuron action potential magnetic sensing exterior to whole, live, opaque marine worms for extended periods with no adverse effect. The results lay the groundwork for real-time, noninvasive 3D magnetic mapping of functional mammalian neuronal networks.

  13. RXP-E: a connexin43-binding peptide that prevents action potential propagation block

    DEFF Research Database (Denmark)

    Lewandowski, Rebecca; Procida, Kristina; Vaidyanathan, Ravi

    2008-01-01

    . Separately, RXP-E was concatenated to a cytoplasmic transduction peptide (CTP) for cytoplasmic translocation (CTP-RXP-E). The effect of RXP-E on action potential propagation was assessed by high-resolution optical mapping in monolayers of neonatal rat ventricular myocytes, containing approximately 20......% of randomly distributed myofibroblasts. In contrast to control experiments, when heptanol (2 mmol/L) was added to the superfusate of monolayers loaded with CTP-RXP-E, action potential propagation was maintained, albeit at a slower velocity. Similarly, intracellular acidification (pH(i) 6.2) caused a loss...... of action potential propagation in control monolayers; however, propagation was maintained in CTP-RXP-E-treated cells, although at a slower rate. Patch-clamp experiments revealed that RXP-E did not prevent heptanol-induced block of sodium currents, nor did it alter voltage dependence or amplitude of Kir2...

  14. Improving Cardiac Action Potential Measurements: 2D and 3D Cell Culture.

    Science.gov (United States)

    Daily, Neil J; Yin, Yue; Kemanli, Pinar; Ip, Brian; Wakatsuki, Tetsuro

    2015-11-01

    Progress in the development of assays for measuring cardiac action potential is crucial for the discovery of drugs for treating cardiac disease and assessing cardiotoxicity. Recently, high-throughput methods for assessing action potential using induced pluripotent stem cell (iPSC) derived cardiomyocytes in both two-dimensional monolayer cultures and three-dimensional tissues have been developed. We describe an improved method for assessing cardiac action potential using an ultra-fast cost-effective plate reader with commercially available dyes. Our methods improve dramatically the detection of the fluorescence signal from these dyes and make way for the development of more high-throughput methods for cardiac drug discovery and cardiotoxicity.

  15. A Parametric Computational Model of the Action Potential of Pacemaker Cells.

    Science.gov (United States)

    Ai, Weiwei; Patel, Nitish D; Roop, Partha S; Malik, Avinash; Andalam, Sidharta; Yip, Eugene; Allen, Nathan; Trew, Mark L

    2018-01-01

    A flexible, efficient, and verifiable pacemaker cell model is essential to the design of real-time virtual hearts that can be used for closed-loop validation of cardiac devices. A new parametric model of pacemaker action potential is developed to address this need. The action potential phases are modeled using hybrid automaton with one piecewise-linear continuous variable. The model can capture rate-dependent dynamics, such as action potential duration restitution, conduction velocity restitution, and overdrive suppression by incorporating nonlinear update functions. Simulated dynamics of the model compared well with previous models and clinical data. The results show that the parametric model can reproduce the electrophysiological dynamics of a variety of pacemaker cells, such as sinoatrial node, atrioventricular node, and the His-Purkinje system, under varying cardiac conditions. This is an important contribution toward closed-loop validation of cardiac devices using real-time heart models.

  16. An indirect component in the evoked compound action potential of the vagal nerve

    Science.gov (United States)

    Ordelman, Simone C. M. A.; Kornet, Lilian; Cornelussen, Richard; Buschman, Hendrik P. J.; Veltink, Peter H.

    2010-12-01

    The vagal nerve plays a vital role in the regulation of the cardiovascular system. It not only regulates the heart but also sends sensory information from the heart back to the brain. We hypothesize that the evoked vagal nerve compound action potential contains components that are indirect via the brain stem or coming via the neural network on the heart. In an experimental study of 15 pigs, we identified four components in the evoked compound action potentials. The fourth component was found to be an indirect component, which came from the periphery. The latency of the indirect component increased when heart rate and contractility were decreased by burst stimulation (P = 0.01; n = 7). When heart rate and contractility were increased by dobutamine administration, the latency of the indirect component decreased (P = 0.01; n = 9). This showed that the latency of the indirect component of the evoked compound action potentials may relate to the state of the cardiovascular system.

  17. Removing the gauge parameter dependence of the effective potential by a field redefinition

    DEFF Research Database (Denmark)

    Nielsen, N. K.

    2014-01-01

    The gauge parameter dependence of the effective potential is determined by partial differential equations involving also the Higgs boson field expectation value. Solving these equations by the method of characteristics leads to elimination of the gauge parameter dependence of the effective...

  18. A phantom axon setup for validating models of action potential recordings.

    Science.gov (United States)

    Rossel, Olivier; Soulier, Fabien; Bernard, Serge; Guiraud, David; Cathébras, Guy

    2016-08-01

    Electrode designs and strategies for electroneurogram recordings are often tested first by computer simulations and then by animal models, but they are rarely implanted for long-term evaluation in humans. The models show that the amplitude of the potential at the surface of an axon is higher in front of the nodes of Ranvier than at the internodes; however, this has not been investigated through in vivo measurements. An original experimental method is presented to emulate a single fiber action potential in an infinite conductive volume, allowing the potential of an axon to be recorded at both the nodes of Ranvier and the internodes, for a wide range of electrode-to-fiber radial distances. The paper particularly investigates the differences in the action potential amplitude along the longitudinal axis of an axon. At a short radial distance, the action potential amplitude measured in front of a node of Ranvier is two times larger than in the middle of two nodes. Moreover, farther from the phantom axon, the measured action potential amplitude is almost constant along the longitudinal axis. The results of this new method confirm the computer simulations, with a correlation of 97.6 %.

  19. The different intracellular action potentials of fast and slow muscle fibres = Différences entre les potentiels d'action intracellulaires de fibres musculaires rapides et lentes

    NARCIS (Netherlands)

    Wallinga, W.; Gielen, Frans L.H.; Wirtz, Peter; de Jong, Paul; Broenink, Johannes F.

    1985-01-01

    The time course of the intracellular action potential was studied quantitatively, because it is an important factor in the generation of electromyographic signals. In in vivo preparations of the m. EDL and m. soleus of the rat single motor units were stimulated and intracellular action potentials

  20. Incorporated fish oil fatty acids prevent action potential shortening induced by circulating fish oil fatty acids

    Directory of Open Access Journals (Sweden)

    Hester M Den Ruijter

    2010-11-01

    Full Text Available Increased consumption of fatty fish, rich in omega-3 polyunsaturated fatty acids (3-PUFAs reduces the severity and number of arrhythmias. Long term 3-PUFA-intake modulates the activity of several cardiac ion channels leading to cardiac action potential shortening. Circulating 3-PUFAs in the bloodstream and incorporated 3-PUFAs in the cardiac membrane have a different mechanism to shorten the action potential. It is, however, unknown whether circulating 3-PUFAs in the bloodstream enhance or diminish the effects of incorporated 3-PUFAs. In the present study, we address this issue. Rabbits were fed a diet rich in fish oil (3 or sunflower oil (9, as control for 3 weeks. Ventricular myocytes were isolated by enzymatic dissociation and action potentials were measured using the perforated patch clamp technique in the absence and presence of acutely administered 3-PUFAs. Plasma of 3 fed rabbits contained more free eicosapentaenoic acid (EPA and isolated myocytes of 3 fed rabbits contained higher amounts of both EPA and docosahexaenoic acid (DHA in their sarcolemma compared to control. In the absence of acutely administered fatty acids, 3 myocytes had a shorter action potential with a more negative plateau than 9 myocytes. In the 9 myocytes, but not in the 3 myocytes, acute administration of a mixture of EPA+DHA shortened the action potential significantly. From these data we conclude that incorporated 3-PUFAs into the sarcolemma and acutely administered 3 fatty acids do not have a cumulative effect on action potential duration and morphology. As a consequence, patients with a high cardiac 3-PUFA status will probably not benefit from short term 3 supplementation as an antiarrhythmic therapy.

  1. Incorporated fish oil fatty acids prevent action potential shortening induced by circulating fish oil fatty acids.

    Science.gov (United States)

    Den Ruijter, Hester M; Verkerk, Arie O; Coronel, Ruben

    2010-01-01

    Increased consumption of fatty fish, rich in omega-3-polyunsaturated fatty acids (ω3-PUFAs) reduces the severity and number of arrhythmias. Long-term ω3-PUFA-intake modulates the activity of several cardiac ion channels leading to cardiac action potential shortening. Circulating ω3-PUFAs in the bloodstream and incorporated ω3-PUFAs in the cardiac membrane have a different mechanism to shorten the action potential. It is, however, unknown whether circulating ω3-PUFAs in the bloodstream enhance or diminish the effects of incorporated ω3-PUFAs. In the present study, we address this issue. Rabbits were fed a diet rich in fish oil (ω3) or sunflower oil (ω9, as control) for 3 weeks. Ventricular myocytes were isolated by enzymatic dissociation and action potentials were measured using the perforated patch-clamp technique in the absence and presence of acutely administered ω3-PUFAs. Plasma of ω3 fed rabbits contained more free eicosapentaenoic acid (EPA) and isolated myocytes of ω3 fed rabbits contained higher amounts of both EPA and docosahexaenoic acid (DHA) in their sarcolemma compared to control. In the absence of acutely administered fatty acids, ω3 myocytes had a shorter action potential with a more negative plateau than ω9 myocytes. In the ω9 myocytes, but not in the ω3 myocytes, acute administration of a mixture of EPA + DHA shortened the action potential significantly. From these data we conclude that incorporated ω3-PUFAs into the sarcolemma and acutely administered ω3 fatty acids do not have a cumulative effect on action potential duration and morphology. As a consequence, patients with a high cardiac ω3-PUFA status will probably not benefit from short term ω3 supplementation as an antiarrhythmic therapy.

  2. Channel sialic acids limit hERG channel activity during the ventricular action potential.

    Science.gov (United States)

    Norring, Sarah A; Ednie, Andrew R; Schwetz, Tara A; Du, Dongping; Yang, Hui; Bennett, Eric S

    2013-02-01

    Activity of human ether-a-go-go-related gene (hERG) 1 voltage-gated K(+) channels is responsible for portions of phase 2 and phase 3 repolarization of the human ventricular action potential. Here, we questioned whether and how physiologically and pathophysiologically relevant changes in surface N-glycosylation modified hERG channel function. Voltage-dependent hERG channel gating and activity were evaluated as expressed in a set of Chinese hamster ovary (CHO) cell lines under conditions of full glycosylation, no sialylation, no complex N-glycans, and following enzymatic deglycosylation of surface N-glycans. For each condition of reduced glycosylation, hERG channel steady-state activation and inactivation relationships were shifted linearly by significant depolarizing ∼9 and ∼18 mV, respectively. The hERG window current increased significantly by 50-150%, and the peak shifted by a depolarizing ∼10 mV. There was no significant change in maximum hERG current density. Deglycosylated channels were significantly more active (20-80%) than glycosylated controls during phases 2 and 3 of action potential clamp protocols. Simulations of hERG current and ventricular action potentials corroborated experimental data and predicted reduced sialylation leads to a 50-70-ms decrease in action potential duration. The data describe a novel mechanism by which hERG channel gating is modulated through physiologically and pathophysiologically relevant changes in N-glycosylation; reduced channel sialylation increases hERG channel activity during the action potential, thereby increasing the rate of action potential repolarization.

  3. A fast Na+/Ca2+-based action potential in a marine diatom.

    Directory of Open Access Journals (Sweden)

    Alison R Taylor

    Full Text Available BACKGROUND: Electrical impulses in animals play essential roles in co-ordinating an array of physiological functions including movement, secretion, environmental sensing and development. Underpinning many of these electrical signals is a fast Na+-based action potential that has been fully characterised only in cells associated with the neuromuscular systems of multicellular animals. Such rapid action potentials are thought to have evolved with the first metazoans, with cnidarians being the earliest representatives. The present study demonstrates that a unicellular protist, the marine diatom Odontella sinensis, can also generate a fast Na+/Ca2+ based action potential that has remarkably similar biophysical and pharmacological properties to invertebrates and vertebrate cardiac and skeletal muscle cells. METHODOLOGY/PRINCIPAL FINDINGS: The kinetic, ionic and pharmacological properties of the rapid diatom action potential were examined using single electrode current and voltage clamp techniques. Overall, the characteristics of the fast diatom currents most closely resemble those of vertebrate and invertebrate muscle Na+/Ca2+ currents. CONCLUSIONS/SIGNIFICANCE: This is the first demonstration of voltage-activated Na+ channels and the capacity to generate fast Na+-based action potentials in a unicellular photosynthetic organism. The biophysical and pharmacological characteristics together with the presence of a voltage activated Na+/Ca2+ channel homologue in the recently sequenced genome of the diatom Thalassiosira pseudonana, provides direct evidence supporting the hypothesis that this rapid signalling mechanism arose in ancestral unicellular eukaryotes and has been retained in at least two phylogenetically distant lineages of eukaryotes; opisthokonts and the stramenopiles. The functional role of the fast animal-like action potential in diatoms remains to be elucidated but is likely involved in rapid environmental sensing of these widespread and

  4. Recognition of Action as a Bayesian Parameter Estimation Problem over Time

    DEFF Research Database (Denmark)

    Krüger, Volker

    2007-01-01

    In this paper we will discuss two problems related to action recognition: The first problem is the one of identifying in a surveillance scenario whether a person is walking or running and in what rough direction. The second problem is concerned with the recovery of action primitives from observed...... complex actions. Both problems will be discussed within a statistical framework. Bayesian propagation over time offers a framework to treat likelihood observations at each time step and the dynamics between the time steps in a unified manner. The first problem will be approached as a patter recognition...... and tracking task by a Bayesian propagation of the likelihoods. The latter problem will be  approached by explicitly specifying the dynamics while the likelihood measure will give a measure how good each dynamical model fit at each time step. Extensive experimental results show the applicability...

  5. Differential effects of thioridazine enantiomers on action potential duration in rabbit papillary muscle

    DEFF Research Database (Denmark)

    Jensen, Ask Schou; Pennisi, Cristian Pablo; Sevcencu, Cristian

    2015-01-01

    with (+)-thioridazine. In this study we for the first time investigate the cardiotoxicity of the isolated thioridazine enantiomers and show their effects on ventricular repolarization. The effects of (+)-thioridazine, (-)-thioridazine, and racemate on the rabbit ventricular action potential duration (APD) were...... investigated in a randomized controlled blinded experiment. Action potentials were measured in papillary muscles isolated from 21 female rabbits, and the drug effect on 90% APD in comparison with control (DeltaDelta-APD90) was evaluated. Increasing concentrations of (+)-thioridazine and the racemate caused...

  6. Action Potential Recording and Pro-arrhythmia Risk Analysis in Human Ventricular Trabeculae.

    Science.gov (United States)

    Qu, Yusheng; Page, Guy; Abi-Gerges, Najah; Miller, Paul E; Ghetti, Andre; Vargas, Hugo M

    2017-01-01

    To assess drug-induced pro-arrhythmic risk, especially Torsades de Pointe (TdP), new models have been proposed, such as in-silico modeling of ventricular action potential (AP) and stem cell-derived cardiomyocytes (SC-CMs). Previously we evaluated the electrophysiological profile of 15 reference drugs in hESC-CMs and hiPSC-CMs for their effects on intracellular AP and extracellular field potential, respectively. Our findings indicated that SC-CMs exhibited immature phenotype and had the propensity to generate false positives in predicting TdP risk. To expand our knowledge with mature human cardiac tissues for drug-induced pro-arrhythmic risk assessment, human ventricular trabeculae (hVT) from ethically consented organ donors were used to evaluate the effects of the same 15 drugs (8 torsadogenic, 5 non-torsadogenic, and 2 discovery molecules) on AP parameters at 1 and 2 Hz. Each drug was tested blindly with 4 concentrations in duplicate trabeculae from 2 hearts. To identify the pro-arrhythmic risk of each drug, a pro-arrhythmic score was calculated as the weighted sum of percent drug-induced changes compared to baseline in various AP parameters, including AP duration and recognized pro-arrhythmia predictors such as triangulation, beat-to-beat variability and incidence of early-afterdepolarizations, at each concentration. In addition, to understand the translation of this preclinical hVT AP-based model to clinical studies, a ratio that relates each testing concentration to the human therapeutic unbound Cmax (Cmax) was calculated. At a ratio of 10, for the 8 torsadogenic drugs, 7 were correctly identified by the pro-arrhythmic score; 1 was mislabeled. For the 5 non-torsadogenic drugs, 4 were correctly identified as safe; 1 was mislabeled. Calculation of sensitivity, specificity, positive predictive value, and negative predictive value indicated excellent performance. For example, at a ratio of 10, scores for sensitivity, specificity, positive predictive value and

  7. Investigating a Potential Auxin-Related Mode of Hormetic/Inhibitory Action of the Phytotoxin Parthenin.

    Science.gov (United States)

    Belz, Regina G

    2016-01-01

    Parthenin is a metabolite of Parthenium hysterophorus and is believed to contribute to the weed's invasiveness via allelopathy. Despite the potential of parthenin to suppress competitors, low doses stimulate plant growth. This biphasic action was hypothesized to be auxin-like and, therefore, an auxin-related mode of parthenin action was investigated using two approaches: joint action experiments with Lactuca sativa, and dose-response experiments with auxin/antiauxin-resistant Arabidopsis thaliana genotypes. The joint action approach comprised binary mixtures of subinhibitory doses of the auxin 3-indoleacetic acid (IAA) mixed with parthenin or one of three reference compounds [indole-3-butyric acid (IBA), 2,3,5-triiodobenzoic acid (TIBA), 2-(p-chlorophenoxy)-2-methylpropionic acid (PCIB)]. The reference compounds significantly interacted with IAA at all doses, but parthenin interacted only at low doses indicating that parthenin hormesis may be auxin-related, in contrast to its inhibitory action. The genetic approach investigated the response of four auxin/antiauxin-resistant mutants and a wildtype to parthenin or two reference compounds (IAA, PCIB). The responses of mutant plants to the reference compounds confirmed previous reports, but differed from the responses observed for parthenin. Parthenin stimulated and inhibited all mutants independent of resistance. This provided no indication for an auxin-related action of parthenin. Therefore, the hypothesis of an auxin-related inhibitory action of parthenin was rejected in two independent experimental approaches, while the hypothesis of an auxin-related stimulatory effect could not be rejected.

  8. Model parameters of technical and tactical actions in the competitive activities of volleyball players

    Directory of Open Access Journals (Sweden)

    Doroshenko E.Iu.

    2013-10-01

    Full Text Available The application of modeling of technical and tactical actions as one of the leading components of the control system of competitive activities of highly skilled volleyball players. It is show that the proposed modeling techniques can generate the optimum orientation of the training process with the use of specialized tools at different stages of the annual cycle of training. In a study based on official statistics volleyball tournament World League in 2012 years. It is recommended to be oriented on the followings model indexes of actions of command and sportsmen: general amount of the collected glasses (170 - 190; amount of glasses, collected in an attack (139 - 157; amount of glasses, collected at blocking (12 - 24; amount of glasses, collected from a serve (9 - 17; the middle index of efficiency is protective actions (at the reception of ball from a serve -58,29%. It is shown that the performance of technical and tactical actions can be used as a model in the management of the process of training and competitive volleyball elite athletes.

  9. Noise Enhances Action Potential Generation in Mouse Sensory Neurons via Stochastic Resonance.

    Science.gov (United States)

    Onorato, Irene; D'Alessandro, Giuseppina; Di Castro, Maria Amalia; Renzi, Massimiliano; Dobrowolny, Gabriella; Musarò, Antonio; Salvetti, Marco; Limatola, Cristina; Crisanti, Andrea; Grassi, Francesca

    2016-01-01

    Noise can enhance perception of tactile and proprioceptive stimuli by stochastic resonance processes. However, the mechanisms underlying this general phenomenon remain to be characterized. Here we studied how externally applied noise influences action potential firing in mouse primary sensory neurons of dorsal root ganglia, modelling a basic process in sensory perception. Since noisy mechanical stimuli may cause stochastic fluctuations in receptor potential, we examined the effects of sub-threshold depolarizing current steps with superimposed random fluctuations. We performed whole cell patch clamp recordings in cultured neurons of mouse dorsal root ganglia. Noise was added either before and during the step, or during the depolarizing step only, to focus onto the specific effects of external noise on action potential generation. In both cases, step + noise stimuli triggered significantly more action potentials than steps alone. The normalized power norm had a clear peak at intermediate noise levels, demonstrating that the phenomenon is driven by stochastic resonance. Spikes evoked in step + noise trials occur earlier and show faster rise time as compared to the occasional ones elicited by steps alone. These data suggest that external noise enhances, via stochastic resonance, the recruitment of transient voltage-gated Na channels, responsible for action potential firing in response to rapid step-wise depolarizing currents.

  10. Propagated repolarization of simulated action potentials in cardiac muscle and smooth muscle

    Directory of Open Access Journals (Sweden)

    Kalloor Bijoy

    2005-02-01

    Full Text Available Abstract Background Propagation of repolarization is a phenomenon that occurs in cardiac muscle. We wanted to test whether this phenomenon would also occur in our model of simulated action potentials (APs of cardiac muscle (CM and smooth muscle (SM generated with the PSpice program. Methods A linear chain of 5 cells was used, with intracellular stimulation of cell #1 for the antegrade propagation and of cell #5 for the retrograde propagation. The hyperpolarizing stimulus parameters applied for termination of the AP in cell #5 were varied over a wide range in order to generate strength / duration (S/D curves. Because it was not possible to insert a second "black box" (voltage-controlled current source into the basic units representing segments of excitable membrane that would allow the cells to respond to small hyperpolarizing voltages, gap-junction (g.j. channels had to be inserted between the cells, represented by inserting a resistor (Rgj across the four cell junctions. Results Application of sufficient hyperpolarizing current to cell #5 to bring its membrane potential (Vm to within the range of the sigmoidal curve of the Na+ conductance (CM or Ca++ conductance (SM terminated the AP in cell #5 in an all-or-none fashion. If there were no g.j. channels (Rgj = ∞, then only cell #5 repolarized to its stable resting potential (RP; -80 mV for CM and -55 mV for SM. The positive junctional cleft potential (VJC produced only a small hyperpolarization of cell #4. However, if many g.j. channels were inserted, more hyperpolarizing current was required (for a constant duration to repolarize cell #5, but repolarization then propagated into cells 4, 3, 2, and 1. When duration of the pulses was varied, a typical S/D curve, characteristic of excitable membranes, was produced. The chronaxie measured from the S/D curve was about 1.0 ms, similar to that obtained for muscle membranes. Conclusions These experiments demonstrate that normal antegrade propagation of

  11. Latent semantics of action verbs reflect phonetic parameters of intensity and emotional content

    National Research Council Canada - National Science Library

    Petersen, Michael Kai

    2015-01-01

    .... As both the shape and movements of objects have been found to be associated with phonetic contrasts already in toddlers, this study explores whether articulatory and acoustic parameters may likewise...

  12. Inhibition by TRPA1 agonists of compound action potentials in the frog sciatic nerve

    Energy Technology Data Exchange (ETDEWEB)

    Matsushita, Akitomo; Ohtsubo, Sena; Fujita, Tsugumi; Kumamoto, Eiichi, E-mail: kumamote@cc.saga-u.ac.jp

    2013-04-26

    Highlights: •TRPA1 agonists inhibited compound action potentials in frog sciatic nerves. •This inhibition was not mediated by TRPA1 channels. •This efficacy was comparable to those of lidocaine and cocaine. •We found for the first time an ability of TRPA1 agonists to inhibit nerve conduction. -- Abstract: Although TRPV1 and TRPM8 agonists (vanilloid capsaicin and menthol, respectively) at high concentrations inhibit action potential conduction, it remains to be unknown whether TRPA1 agonists have a similar action. The present study examined the actions of TRPA1 agonists, cinnamaldehyde (CA) and allyl isothiocyanate (AITC), which differ in chemical structure from each other, on compound action potentials (CAPs) recorded from the frog sciatic nerve by using the air-gap method. CA and AITC concentration-dependently reduced the peak amplitude of the CAP with the IC{sub 50} values of 1.2 and 1.5 mM, respectively; these activities were resistant to a non-selective TRP antagonist ruthenium red or a selective TRPA1 antagonist HC-030031. The CA and AITC actions were distinct in property; the latter but not former action was delayed in onset and partially reversible, and CA but not AITC increased thresholds to elicit CAPs. A CAP inhibition was seen by hydroxy-α-sanshool (by 60% at 0.05 mM), which activates both TRPA1 and TRPV1 channels, a non-vanilloid TRPV1 agonist piperine (by 20% at 0.07 mM) and tetrahydrolavandulol (where the six-membered ring of menthol is opened; IC{sub 50} = 0.38 mM). It is suggested that TRPA1 agonists as well as TRPV1 and TRPM8 agonists have an ability to inhibit nerve conduction without TRP activation, although their agonists are quite different in chemical structure from each other.

  13. Equivalent local potentials and phase approach to low-energy scattering parameters

    Energy Technology Data Exchange (ETDEWEB)

    Jana, A.K.; Nandi, T.K.; Paul, A.K.; Talukdar, B. (Department of Physics, Santiniketan, West Bengal (India))

    1994-01-01

    It is shown that the use of the McTavish-Kermode-Melhem-type equivalent local potentials linearizes algorithms of the variable-phase approach needed to compute the low-energy scattering parameters. A case study is presented to demonstrate the merit of the linearized equations, with particular emphasis on the relationship between the interpolating scattering length function and potential functions. (Author).

  14. One-parameter families of supersymmetric isospectral potentials from Riccati solutions in function composition form

    Energy Technology Data Exchange (ETDEWEB)

    Rosu, Haret C., E-mail: hcr@ipicyt.edu.mx [IPICYT, Instituto Potosino de Investigacion Cientifica y Tecnologica, Camino a la presa San José 2055, Col. Lomas 4a Sección, 78216 San Luis Potosí, S.L.P. (Mexico); Mancas, Stefan C., E-mail: mancass@erau.edu [Department of Mathematics, Embry–Riddle Aeronautical University, Daytona Beach, FL 32114-3900 (United States); Chen, Pisin, E-mail: pisinchen@phys.ntu.edu.tw [Leung Center for Cosmology and Particle Astrophysics (LeCosPA) and Department of Physics, National Taiwan University, Taipei 10617, Taiwan (China)

    2014-04-15

    In the context of supersymmetric quantum mechanics, we define a potential through a particular Riccati solution of the composition form (F∘f)(x)=F(f(x)) and obtain a generalized Mielnik construction of one-parameter isospectral potentials when we use the general Riccati solution. Some examples for special cases of F and f are given to illustrate the method. An interesting result is obtained in the case of a parametric double well potential generated by this method, for which it is shown that the parameter of the potential controls the heights of the localization probability in the two wells, and for certain values of the parameter the height of the localization probability can be higher in the smaller well. -- Highlights: •Function-composition generalization of parametric isospectral potentials is presented. •Mielnik one-parameter family of harmonic potentials is obtained as a particular case. •Graphical discussion of regular and singular regions in the parameter space is given.

  15. The Transformative Potential of Action Research and ICT in the Second Language (L2) Classroom

    Science.gov (United States)

    Farren, Margaret; Crotty, Yvonne; Kilboy, Laura

    2015-01-01

    This study shows the transformative potential of action research and information and communications technology (ICT) in the second language (L2) classroom. Two enquiries from teacher-researchers are detailed in the article. Their engagement in a collaborative professional development Masters programme was pivotal in designing and implementing ICT…

  16. Viewing Objects and Planning Actions: On the Potentiation of Grasping Behaviours by Visual Objects

    Science.gov (United States)

    Makris, Stergios; Hadar, Aviad A.; Yarrow, Kielan

    2011-01-01

    How do humans interact with tools? Gibson (1979) suggested that humans perceive directly what tools afford in terms of meaningful actions. This "affordances" hypothesis implies that visual objects can potentiate motor responses even in the absence of an intention to act. Here we explore the temporal evolution of motor plans afforded by common…

  17. Preservation of cardiac function by prolonged action potentials in mice deficient of KChIP2

    DEFF Research Database (Denmark)

    Grubb, Søren Jahn; Aistrup, Gary L; Koivumäki, Jussi T

    2015-01-01

    Inherited ion channelopathies and electrical remodeling in heart disease alter the cardiac action potential with important consequences for excitation-contraction coupling. Potassium channel-interacting protein 2 (KChIP2) is reduced in heart failure and interacts under physiological conditions...

  18. A dual potassium channel activator improves repolarization reserve and normalizes ventricular action potentials

    DEFF Research Database (Denmark)

    Calloe, Kirstine; Di Diego, José M; Hansen, Rie Schultz

    2016-01-01

    in cultured canine cardiac myocytes and determined whether a dual K(+) current activator can normalize K(+) currents and restore action potential (AP) configuration. METHODS AND RESULTS: Ventricular myocytes were isolated and cultured for up to 48h. Current and voltage clamp recordings were made using patch...

  19. Action potential generation requires a high sodium channel density in the axon initial segment

    NARCIS (Netherlands)

    Kole, Maarten H. P.; Ilschner, Susanne U.; Kampa, Björn M.; Williams, Stephen R.; Ruben, Peter C.; Stuart, Greg J.

    2008-01-01

    The axon initial segment ( AIS) is a specialized region in neurons where action potentials are initiated. It is commonly assumed that this process requires a high density of voltage-gated sodium ( Na(+)) channels. Paradoxically, the results of patch-clamp studies suggest that the Na(+) channel

  20. The neuron-level phenomena underlying cognition and consciousness: synaptic activity and the action potential.

    Science.gov (United States)

    Cook, N D

    2008-05-15

    An unusual property of the neuron is its capability for cell-to-cell communication via synapses, known to be the neuron-level "protophenomenon" underlying the brain-level "real phenomenon" of cognition. The temporal synchronization of such synaptic activity is the leading candidate for explaining "cognitive binding" and therefore the unity of mind. An equally-unusual property of the neuron is the action potential, the means by which the neuron sends a signal down the axon. Although infrequently noted by researchers in relation to consciousness, signal propagation within the neuron entails the momentary permeability of the neuronal membrane, allowing a massive influx of charged ions into the cellular interior. Such openness to the extracellular world is arguably the protophenomenon of neuronal "sentience," literally, feeling the charge-state of the electrochemical environment. Sensitivity to the external pH is a common feature of all living cells, but is greatly amplified during the neuron's action potential. Synchronization of the action potentials of the same neurons that are involved in cognitive binding is the likely mechanism by which the sentience of individual neurons is coordinated into the brain-level phenomenon of subjective awareness. I conclude that a proper understanding of the permeability of the neuronal membrane during the action potential is as important for consciousness studies as is a proper understanding of synaptic transmission for the explication of the cognition made possible by neurons.

  1. Combined action potential- and dynamic-clamp for accurate computational modelling of the cardiac IKr current.

    Science.gov (United States)

    Bartolucci, Chiara; Altomare, Claudia; Bennati, Marco; Furini, Simone; Zaza, Antonio; Severi, Stefano

    2015-02-01

    In the present work Action-Potential clamp (APC) and Dynamic clamp (DC) were used in combination in order to optimize the Luo-Rudy (LRd) mathematical formulation of the guinea-pig rapid delayed rectifier K(+) current (IKr), and to validate the optimized model. To this end, IKr model parameters were adjusted to fit the experimental E4031-sensitive current (IE4031) recorded under APC in guinea-pig myocytes. Currents generated by LRd model (ILRd) and the optimized one (IOpt) were then compared by testing their suitability to replace IE4031 under DC. Under APC, ILRd was significantly larger than IE4031 (mean current densities 0.51±0.01 vs 0.21±0.05pA/pF; p<0.001), mainly because of different rectification. IOpt mean density (0.17±0.01pA/pF) was similar to the IE4031 one (NS); moreover, IOpt accurately reproduced IE4031 distribution along the different AP phases. Models were then compared under DC by blocking native IKr (5μM E4031) and replacing it with ILRd or IOpt. Whereas injection of ILRd overshortened AP duration (APD90) (by 25% of its pre-block value), IOpt injection restored AP morphology and duration to overlap pre-block values. This study highlights the power of APC and DC for the identification of reliable formulations of ionic current models. An optimized model of IKr has been obtained which fully reversed E4031 effects on the AP. The model strongly diverged from the widely used Luo-Rudy formulation; this can be particularly relevant to the in silico analysis of AP prolongation caused by IKr blocking or alterations. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Effects of estragole on the compound action potential of the rat sciatic nerve

    Directory of Open Access Journals (Sweden)

    J.H. Leal-Cardoso

    2004-08-01

    Full Text Available Estragole, a relatively nontoxic terpenoid ether, is an important constituent of many essential oils with widespread applications in folk medicine and aromatherapy and known to have potent local anesthetic activity. We investigated the effects of estragole on the compound action potential (CAP of the rat sciatic nerve. The experiments were carried out on sciatic nerves dissected from Wistar rats. Nerves, mounted in a moist chamber, were stimulated at a frequency of 0.2 Hz, with electric pulses of 50-100-µs duration at 10-20 V, and evoked CAP were monitored on an oscilloscope and recorded on a computer. CAP control parameters were: peak-to-peak amplitude (PPA, 9.9 ± 0.55 mV (N = 15, conduction velocity, 92.2 ± 4.36 m/s (N = 15, chronaxy, 45.6 ± 3.74 µs (N = 5, and rheobase, 3.9 ± 0.78 V (N = 5. Estragole induced a dose-dependent blockade of the CAP. At 0.6 mM, estragole had no demonstrable effect. At 2.0 and 6.0 mM estragole, PPA was significantly reduced at the end of 180-min exposure of the nerve to the drug to 85.6 ± 3.96 and 13.04 ± 1.80% of control, respectively. At 4.0 mM, estragole significantly altered PPA, conduction velocity, chronaxy, and rheobase (P <= 0.05, ANOVA; N = 5 to 49.3 ± 6.21 and 77.7 ± 3.84, 125.9 ± 10.43 and 116.7 ± 4.59%, of control, respectively. All of these effects developed slowly and were reversible upon a 300-min wash-out. The data show that estragole dose-dependently blocks nerve excitability.

  3. Ecstasy and methamphetamine elicit action potential bursts via different mechanisms in a central snail neuron.

    Science.gov (United States)

    Lin, Pei-Lin; Tsai, Ming-Cheng; Lu, Guan-Ling; Lu, Dah-Yuu; Chuang, Chieh-Min; Yang, Han-Yin; Huang, Shiang-Suo; Chen, Yi-Hung

    2010-01-01

    This study sought to determine the effects of (+) methamphetamine (METH) and its ring-substituted analog (+/-)3,4-methylenedioxymethamphetamine (MDMA; ecstasy) on electrophysiological behavior and their relationships to second messenger systems in an identifiable RP4 neuron of the African snail, Achatina fulica Ferussac. Extracellular application of MDMA at 1mM and METH at 3mM elicited action potential bursts that were not blocked after immersing the neurons in Ca(2+)-free solution. Notably, MDMA- (1mM) elicited action potential bursts were blocked by pretreatment with the protein kinase C (PKC) inhibitors chelerythrine (20 microM) and Ro 31-8220 (20 microM), but not by the PKA inhibitors KT-5720 (10 microM) and H89 (10 microM). The PKC activator phorbol 12,13-dibutyrate (PDBu; 3 microM), but not the PKA activator forskolin (50 microM), facilitated the induction of bursts elicited by MDMA at a lower concentration (0.3mM). In contrast, METH- (3mM) elicited action potential bursts were blocked by pretreatment with KT-5720 (10 microM) and H89 (10 microM), but not by chelerythrine (20 microM) and Ro 31-8220 (20 microM). Forskolin (50 microM), but not PDBu (3 microM) facilitated the induction of bursts elicited by METH at a lower concentration (1mM). Tetraethylammonium chloride (TEA), a blocker of the delayed rectifying K(+) current (I(KD)), did not elicit bursts at a concentration of 5mM but did facilitate the induction of action potential bursts elicited by both METH and MDMA. Voltage clamp studies revealed that both METH and MDMA decreased the TEA-sensitive I(KD) of the RP4 neuron. Forskolin (50 microM) or dibutyryl cAMP (1mM), a membrane-permeable cAMP analog, alone did not elicit action potential bursts. However, co-administration with forskolin (50 microM) and TEA (5mM) or co-administration with dibutyryl cAMP (1mM) and TEA (50mM) elicited action potential bursts in the presence of the PKC inhibitor chelerythrine (20 microM). Similarly, PDBu (10 microM) or phorbol

  4. Axonal sodium channel distribution shapes the depolarized action potential threshold of dentate granule neurons.

    Science.gov (United States)

    Kress, Geraldine J; Dowling, Margaret J; Eisenman, Lawrence N; Mennerick, Steven

    2010-04-01

    Intrinsic excitability is a key feature dictating neuronal response to synaptic input. Here we investigate the recent observation that dentate granule neurons exhibit a more depolarized voltage threshold for action potential initiation than CA3 pyramidal neurons. We find no evidence that tonic GABA currents, leak or voltage-gated potassium conductances, or the expression of sodium channel isoform differences can explain this depolarized threshold. Axonal initial segment voltage-gated sodium channels, which are dominated by the Na(V)1.6 isoform in both cell types, distribute more proximally and exhibit lower overall density in granule neurons than in CA3 neurons. To test possible contributions of sodium channel distributions to voltage threshold and to test whether morphological differences participate, we performed simulations of dentate granule neurons and of CA3 pyramidal neurons. These simulations revealed that cell morphology and sodium channel distribution combine to yield the characteristic granule neuron action potential upswing and voltage threshold. Proximal axon sodium channel distribution strongly contributes to the higher voltage threshold of dentate granule neurons for two reasons. First, action potential initiation closer to the somatodendritic current sink causes the threshold of the initiating axon compartment to rise. Second, the proximity of the action potential initiation site to the recording site causes somatic recordings to more faithfully reflect the depolarized threshold of the axon than in cells like CA3 neurons, with distally initiating action potentials. Our results suggest that the proximal location of axon sodium channels in dentate granule neurons contributes to the intrinsic excitability differences between DG and CA3 neurons and may participate in the low-pass filtering function of dentate granule neurons. (c) 2009 Wiley-Liss, Inc.

  5. Obtaining the Varshni potential function using the 2-body Kaxiras–Pandey parameters

    Directory of Open Access Journals (Sweden)

    TEIK-CHENG LIM

    2009-12-01

    Full Text Available A generalized version of the Varshni potential function was adopted by Kaxiras and Pandey for describing the 2-body energy portion of multi-body condensed matter. The former’s simplicity and resemblance to a Morse potential allows faster computation while the latter’s greater number of parameters allows better curve-fitting of spectroscopic data. This paper shows one set of parameter conversion from the Varshni function to the 2-body portion of the Kaxiras–Pandey function, and vice versa two sets of parameter conversion. The latter two sets reveal good correlation between plotted curves, and were verified by the imposition of equal energy curvatures at equilibrium and equal energy integral from equilibrium to dissociation. These parameter conversions can also be attained more easily by equating the product of indices (for short range and the summation of index reciprocals (for long range.

  6. Mechanisms of action of ligands of potential-dependent sodium channels.

    Science.gov (United States)

    Tikhonov, D B

    2008-06-01

    Potential-dependent sodium channels play a leading role in generating action potentials in excitable cells. Sodium channels are the site of action of a variety of modulator ligands. Despite numerous studies, the mechanisms of action of many modulators remain incompletely understood. The main reason that many important questions cannot be resolved is that there is a lack of precise data on the structures of the channels themselves. Structurally, potential-dependent sodium channels are members of the P-loop channel superfamily, which also include potassium and calcium channels and glutamate receptor channels. Crystallization of a series of potassium channels showed that it was possible to analyze the structures of different members of the superfamily using the "homologous modeling" method. The present study addresses model investigations of the actions of ligands of sodium channels, including tetrodotoxin and batrachotoxin, as well as local anesthetics. Comparison of experimental data on sodium channel ligands with x-ray analysis data allowed us to reach a new level of understanding of the mechanisms of channel modulation and to propose a series of experimentally verifiable hypotheses.

  7. Restitution slope is principally determined by steady-state action potential duration.

    Science.gov (United States)

    Shattock, Michael J; Park, Kyung Chan; Yang, Hsiang-Yu; Lee, Angela W C; Niederer, Steven; MacLeod, Kenneth T; Winter, James

    2017-06-01

    The steepness of the action potential duration (APD) restitution curve and local tissue refractoriness are both thought to play important roles in arrhythmogenesis. Despite this, there has been little recognition of the apparent association between steady-state APD and the slope of the restitution curve. The objective of this study was to test the hypothesis that restitution slope is determined by APD and to examine the relationship between restitution slope, refractoriness and susceptibility to VF. Experiments were conducted in isolated hearts and ventricular myocytes from adult guinea pigs and rabbits. Restitution curves were measured under control conditions and following intervention to prolong (clofilium, veratridine, bretylium, low [Ca]e, chronic transverse aortic constriction) or shorten (catecholamines, rapid pacing) ventricular APD. Despite markedly differing mechanisms of action, all interventions that prolonged the action potential led to a steepening of the restitution curve (and vice versa). Normalizing the restitution curve as a % of steady-state APD abolished the difference in restitution curves with all interventions. Effects on restitution were preserved when APD was modulated by current injection in myocytes pre-treated with the calcium chelator BAPTA-AM - to abolish the intracellular calcium transient. The non-linear relation between APD and the rate of repolarization of the action potential is shown to underpin the common influence of APD on the slope of the restitution curve. Susceptibility to VF was found to parallel changes in APD/refractoriness, rather than restitution slope. Steady-state APD is the principal determinant of the slope of the ventricular electrical restitution curve. In the absence of post-repolarization refractoriness, factors that prolong the action potential would be expected to steepen the restitution curve. However, concomitant changes in tissue refractoriness act to reduce susceptibility to sustained VF. Dependence on

  8. Contribution of action potentials to the extracellular field potential in the nucleus laminaris of barn owl.

    Science.gov (United States)

    Kuokkanen, Paula T; Ashida, Go; Kraemer, Anna; McColgan, Thomas; Funabiki, Kazuo; Wagner, Hermann; Köppl, Christine; Carr, Catherine E; Kempter, Richard

    2017-12-20

    Extracellular field potentials (EFP) are widely used to evaluate in vivo neural activity, but identification of multiple sources and their relative contributions is often ambiguous, making the interpretation of the EFP difficult. We have therefore analyzed a model EFP from a simple brainstem circuit with separable pre- and postsynaptic components to determine if we could isolate its sources. Our previous papers had shown that the barn owl neurophonic largely originates with spikes from input axons and synapses that terminate on the neurons in the nucleus laminaris (NL) (Kuokkanen et al., 2010; 2013; McColgan et al., 2017). To determine how much the postsynaptic NL neurons contributed to the neurophonic, we recorded EFP responses in NL in vivo. Power spectral analyses showed that a small spectral component of the evoked response, between 200 - 700 Hz, could be attributed to the NL neurons' spikes, while NM spikes dominate the EFP at frequencies {greater than or equal to}1 kHz. Thus, spikes of NL neurons and NM axons contribute to the EFP in NL in distinct frequency bands. We conclude that if the spectral components of source types are different and if their activities can be selectively modulated, the identification of EFP sources is possible.

  9. Nonlinear plasma sheath potential in the ASDEX Upgrade 3-strap antenna: a parameter scan

    Science.gov (United States)

    Tierens, W.; Jacquot, J.; Bobkov, V.; Noterdaeme, J. M.; Colas, L.; The ASDEX Upgrade Team

    2017-11-01

    In this paper we use the SSWICH-SW software to calculate the (nonlinear) plasma potential near the ASDEX Upgrade 3-strap antenna for various operating parameters, and compare it with the (linear) parallel electric field strength and the (linear) RF potential. It is believed that the plasma potential is the cause of ion sputtering and additional heat loads on the antenna, and that the parallel electric field strength (as calculated by linear codes without sheath boundary conditions) is a good proxy for the plasma potential, and our results confirm the latter.

  10. Simple techniques suitable for student use to record action potentials from the frog heart.

    Science.gov (United States)

    Yoshida, S

    2001-12-01

    Demonstrating action potentials during class experiments is very educational for science students. It is not easy, however, to obtain a stable intracellular recording of action potentials from the conventionally used skeletal muscle cells, because the tip of a glass microelectrode often comes out or breaks due to muscle contraction. Here, I present a much simpler recording method using a flexible polyethylene electrode with a wide orifice (approximately 1 mm) for a bullfrog heart beating on automaticity. Extracellular recordings of action potentials (electrocardiogram) can be obtained by placing an electrode on the cardiac surface, and transmembrane potentials can be obtained by rupturing the membrane with negative pressure, i.e., whole cell configuration. Once attached to the heart by suction, the polyethylene electrode does not easily come off during contraction of the heart. Perfusion of the heart via the postcaval vein offers us opportunities for observing the effects of either changing ionic compositions of solutions or applying drugs. The techniques shown here provide a simple and convenient way to perform a variety of class experiments.

  11. Label-free optical detection of action potential in mammalian neurons (Conference Presentation)

    Science.gov (United States)

    Batabyal, Subrata; Satpathy, Sarmishtha; Bui, Loan; Kim, Young-Tae; Mohanty, Samarendra K.; Davé, Digant P.

    2017-02-01

    Electrophysiology techniques are the gold standard in neuroscience for studying functionality of a single neuron to a complex neuronal network. However, electrophysiology techniques are not flawless, they are invasive nature, procedures are cumbersome to implement with limited capability of being used as a high-throughput recording system. Also, long term studies of neuronal functionality with aid of electrophysiology is not feasible. Non-invasive stimulation and detection of neuronal electrical activity has been a long standing goal in neuroscience. Introduction of optogenetics has ushered in the era of non-invasive optical stimulation of neurons, which is revolutionizing neuroscience research. Optical detection of neuronal activity that is comparable to electro-physiology is still elusive. A number of optical techniques have been reported recording of neuronal electrical activity but none is capable of reliably measuring action potential spikes that is comparable to electro-physiology. Optical detection of action potential with voltage sensitive fluorescent reporters are potential alternatives to electrophysiology techniques. The heavily rely on secondary reporters, which are often toxic in nature with background fluorescence, with slow response and low SNR making them far from ideal. The detection of one shot (without averaging)-single action potential in a true label-free way has been elusive so far. In this report, we demonstrate the optical detection of single neuronal spike in a cultured mammalian neuronal network without using any exogenous labels. To the best of our knowledge, this is the first demonstration of label free optical detection of single action potentials in a mammalian neuronal network, which was achieved using a high-speed phase sensitive interferometer. We have carried out stimulation and inhibition of neuronal firing using Glutamate and Tetrodotoxin respectively to demonstrate the different outcome (stimulation and inhibition) revealed in

  12. Action-potential discharge in hippocampal CA1 pyramidal neurons: current source-density analysis.

    Science.gov (United States)

    Richardson, T L; Turner, R W; Miller, J J

    1987-11-01

    1. The site of origin of evoked action-potential discharge in hippocampal CA1 pyramidal neurons was investigated using the in vitro rat hippocampal slice preparation. 2. Action-potential discharge in pyramidal cells was evoked by stimulation of efferent pyramidal cell fibers in the alveus (antidromic) or afferent synaptic inputs in stratum oriens (SO) or stratum radiatum (SR). Laminar profiles of evoked extracellular field potentials were recorded at 25-micron intervals along the entire dendrosomatic axis of the pyramidal cell and a one-dimensional current source-density analysis was applied. 3. Suprathreshold stimulation of the alveus evoked an antidromic population spike response and current sink with the shortest peak latency in stratum pyramidale or proximal stratum oriens. A biphasic positive/negative potential associated with a current source/sink was recorded in dendritic regions, with both components increasing in peak latency with distance from the border of stratum pyramidale. 4. Suprathreshold stimulation of SO or SR evoked a population spike response superimposed upon the underlying synaptic depolarization at all levels of the dendrosomatic axis. The shortest latency population spike and current sink were recorded in stratum pyramidale or proximal stratum oriens. In dendritic regions, a biphasic positive/negative potential and current source/sink conducted with increasing latency from the border of stratum pyramidale. 5. A direct comparison of alvear- and SR-evoked responses revealed a basic similarity in population spike potentials and associated sink/source relationships at both the somatic and dendritic level and a similar shift in peak latency of spike components along the pyramidal cell axis. 6. It is concluded that the initial site for generation of a spike along the dendrosomatic axis of the pyramidal cell following antidromic or orthodromic stimulation is in the region of the cell body layer (soma or axon hillock). Action-potential discharge in

  13. Sensitivity analysis of CLIMEX parameters in modeling potential distribution of Phoenix dactylifera L.

    Directory of Open Access Journals (Sweden)

    Farzin Shabani

    Full Text Available Using CLIMEX and the Taguchi Method, a process-based niche model was developed to estimate potential distributions of Phoenix dactylifera L. (date palm, an economically important crop in many counties. Development of the model was based on both its native and invasive distribution and validation was carried out in terms of its extensive distribution in Iran. To identify model parameters having greatest influence on distribution of date palm, a sensitivity analysis was carried out. Changes in suitability were established by mapping of regions where the estimated distribution changed with parameter alterations. This facilitated the assessment of certain areas in Iran where parameter modifications impacted the most, particularly in relation to suitable and highly suitable locations. Parameter sensitivities were also evaluated by the calculation of area changes within the suitable and highly suitable categories. The low temperature limit (DV2, high temperature limit (DV3, upper optimal temperature (SM2 and high soil moisture limit (SM3 had the greatest impact on sensitivity, while other parameters showed relatively less sensitivity or were insensitive to change. For an accurate fit in species distribution models, highly sensitive parameters require more extensive research and data collection methods. Results of this study demonstrate a more cost effective method for developing date palm distribution models, an integral element in species management, and may prove useful for streamlining requirements for data collection in potential distribution modeling for other species as well.

  14. Sensitivity analysis of CLIMEX parameters in modelling potential distribution of Lantana camara L.

    Science.gov (United States)

    Taylor, Subhashni; Kumar, Lalit

    2012-01-01

    A process-based niche model of L. camara L. (lantana), a highly invasive shrub species, was developed to estimate its potential distribution using CLIMEX. Model development was carried out using its native and invasive distribution and validation was carried out with the extensive Australian distribution. A good fit was observed, with 86.7% of herbarium specimens collected in Australia occurring within the suitable and highly suitable categories. A sensitivity analysis was conducted to identify the model parameters that had the most influence on lantana distribution. The changes in suitability were assessed by mapping the regions where the distribution changed with each parameter alteration. This allowed an assessment of where, within Australia, the modification of each parameter was having the most impact, particularly in terms of the suitable and highly suitable locations. The sensitivity of various parameters was also evaluated by calculating the changes in area within the suitable and highly suitable categories. The limiting low temperature (DV0), limiting high temperature (DV3) and limiting low soil moisture (SM0) showed highest sensitivity to change. The other model parameters were relatively insensitive to change. Highly sensitive parameters require extensive research and data collection to be fitted accurately in species distribution models. The results from this study can inform more cost effective development of species distribution models for lantana. Such models form an integral part of the management of invasive species and the results can be used to streamline data collection requirements for potential distribution modelling.

  15. Sensitivity analysis of CLIMEX parameters in modelling potential distribution of Lantana camara L.

    Directory of Open Access Journals (Sweden)

    Subhashni Taylor

    Full Text Available A process-based niche model of L. camara L. (lantana, a highly invasive shrub species, was developed to estimate its potential distribution using CLIMEX. Model development was carried out using its native and invasive distribution and validation was carried out with the extensive Australian distribution. A good fit was observed, with 86.7% of herbarium specimens collected in Australia occurring within the suitable and highly suitable categories. A sensitivity analysis was conducted to identify the model parameters that had the most influence on lantana distribution. The changes in suitability were assessed by mapping the regions where the distribution changed with each parameter alteration. This allowed an assessment of where, within Australia, the modification of each parameter was having the most impact, particularly in terms of the suitable and highly suitable locations. The sensitivity of various parameters was also evaluated by calculating the changes in area within the suitable and highly suitable categories. The limiting low temperature (DV0, limiting high temperature (DV3 and limiting low soil moisture (SM0 showed highest sensitivity to change. The other model parameters were relatively insensitive to change. Highly sensitive parameters require extensive research and data collection to be fitted accurately in species distribution models. The results from this study can inform more cost effective development of species distribution models for lantana. Such models form an integral part of the management of invasive species and the results can be used to streamline data collection requirements for potential distribution modelling.

  16. Label-free optical detection of action potential in mammalian neurons.

    Science.gov (United States)

    Batabyal, Subrata; Satpathy, Sarmishtha; Bui, Loan; Kim, Young-Tae; Mohanty, Samarendra; Bachoo, Robert; Davé, Digant P

    2017-08-01

    We describe an optical technique for label-free detection of the action potential in cultured mammalian neurons. Induced morphological changes due to action potential propagation in neurons are optically interrogated with a phase sensitive interferometric technique. Optical recordings composed of signal pulses mirror the electrical spike train activity of individual neurons in a network. The optical pulses are transient nanoscale oscillatory changes in the optical path length of varying peak magnitude and temporal width. Exogenous application of glutamate to cortical neuronal cultures produced coincident increase in the electrical and optical activity; both were blocked by application of a Na-channel blocker, Tetrodotoxin. The observed transient change in optical path length in a single optical pulse is primarily due to physical fluctuations of the neuronal cell membrane mediated by a yet unknown electromechanical transduction phenomenon. Our analysis suggests a traveling surface wave in the neuronal cell membrane is responsible for the measured optical signal pulses.

  17. Attention-dependent reductions in burstiness and action potential height in macaque area V4

    Science.gov (United States)

    Anderson, Emily B.; Mitchell, Jude F.; Reynolds, John H.

    2013-01-01

    Attention improves the encoding of visual stimuli. One mechanism that is implicated in facilitating sensory encoding is the firing of action potentials in bursts. We tested the hypothesis that when spatial attention is directed to a stimulus, this causes an increase in burst firing to the attended stimulus. To the contrary, we found an attention-dependent reduction in burstiness among putative pyramidal neurons in macaque area V4. We accounted for this using a conductance-based Hodgkin-Huxley style model in which attentional modulation stems from scaling excitation and inhibition. The model exhibited attention-dependent increases in firing rate and made the surprising and correct prediction that when attention is directed into a neuron’s receptive field, this reduces action potential height. The model thus provided a unified explanation for three distinct forms of attentional modulation, two of them novel, and implicates scaling of the responses of excitatory and inhibitory input populations in mediating attention. PMID:23852114

  18. Iridium Oxide Nanotube Electrodes for Highly Sensitive and Prolonged Intracellular Measurement of Action Potentials

    Science.gov (United States)

    Lin, Ziliang Carter; Xie, Chong; Osakada, Yasuko; Cui, Yi; Cui, Bianxiao

    2014-01-01

    Intracellular recording of action potentials is important to understand electrically-excitable cells. Recently, vertical nanoelectrodes have been developed to achieve highly sensitive, minimally invasive, and large scale intracellular recording. It has been demonstrated that the vertical geometry is crucial for the enhanced signal detection. Here we develop nanoelectrodes made up of nanotubes of iridium oxide. When cardiomyocytes are cultured upon those nanotubes, the cell membrane not only wraps around the vertical tubes but also protrudes deep into the hollow center. We show that this geometry enhances cell-electrode coupling and results in measuring much larger intracellular action potentials. The nanotube electrodes afford much longer intracellular access and are minimally invasive, making it possible to achieve stable recording up to an hour in a single session and more than 8 days of consecutive daily recording. This study suggests that the electrode performance can be significantly improved by optimizing the electrode geometry. PMID:24487777

  19. Cardiac action potential repolarization revisited: early repolarization shows all-or-none behaviour.

    Science.gov (United States)

    Trenor, Beatriz; Cardona, Karen; Saiz, Javier; Noble, Denis; Giles, Wayne

    2017-11-01

    In healthy mammalian hearts the action potential (AP) waveform initiates and modulates each contraction, or heartbeat. As a result, AP height and duration are key physiological variables. In addition, rate-dependent changes in ventricular AP duration (APD), and variations in APD at a fixed heart rate are both reliable biomarkers of electrophysiological stability. Present guidelines for the likelihood that candidate drugs will increase arrhythmias rely on small changes in APD and Q-T intervals as criteria for safety pharmacology decisions. However, both of these measurements correspond to the final repolarization of the AP. Emerging clinical evidence draws attention to the early repolarization phase of the action potential (and the J-wave of the ECG) as an additional important biomarker for arrhythmogenesis. Here we provide a mechanistic background to this early repolarization syndrome by summarizing the evidence that both the initial depolarization and repolarization phases of the cardiac action potential can exhibit distinct time- and voltage-dependent thresholds, and also demonstrating that both can show regenerative all-or-none behaviour. An important consequence of this is that not all of the dynamics of action potential repolarization in human ventricle can be captured by data from single myocytes when these results are expressed as 'repolarization reserve'. For example, the complex pattern of cell-to-cell current flow that is responsible for AP conduction (propagation) within the mammalian myocardium can change APD and the Q-T interval of the electrocardiogram alter APD stability, and modulate responsiveness to pharmacological agents (such as Class III anti-arrhythmic drugs). © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

  20. Membrane parameters, signal transmission, and the design of a graded potential neuron

    NARCIS (Netherlands)

    Hateren, J.H. van; Laughlin, S.B.

    1990-01-01

    The large monopolar cells (LMCs) of the fly, Calliphora vicina, visual system transmit graded potentials over distances of up to 1.0 mm. An electrical model was constructed to investigate the design principles relating their membrane parameters to signal transmission and filtering. Using existing

  1. TASK-1 Channels May Modulate Action Potential Duration of Human Atrial Cardiomyocytes

    Science.gov (United States)

    Limberg, Sven H.; Netter, Michael F.; Rolfes, Caroline; Rinné, Susanne; Schlichthörl, Günter; Zuzarte, Marylou; Vassiliou, Timon; Moosdorf, Rainer; Wulf, Hinnerk; Daut, Jürgen; Sachse, Frank B.; Decher, Niels

    2011-01-01

    Background/Aims: Atrial fibrillation is the most common arrhythmia in the elderly, and potassium channels with atrium-specific expression have been discussed as targets to treat atrial fibrillation. Our aim was to characterize TASK-1 channels in human heart and to functionally describe the role of the atrial whole cell current ITASK-1. Methods and Results: Using quantitative PCR, we show that TASK-1 is predominantly expressed in the atria, auricles and atrio-ventricular node of the human heart. Single channel recordings show the functional expression of TASK-1 in right human auricles. In addition, we describe for the first time the whole cell current carried by TASK-1 channels (ITASK-1) in human atrial tissue. We show that ITASK-1 contributes to the sustained outward current IKsus and that ITASK-1 is a major component of the background conductance in human atrial cardiomyocytes. Using patch clamp recordings and mathematical modeling of action potentials, we demonstrate that modulation of ITASK-1 can alter human atrial action potential duration. Conclusion: Due to the lack of ventricular expression and the ability to alter human atrial action potential duration, TASK-1 might be a drug target for the treatment of atrial fibrillation. PMID:22178873

  2. ER Stress-Mediated Signaling: Action Potential and Ca(2+) as Key Players.

    Science.gov (United States)

    Bahar, Entaz; Kim, Hyongsuk; Yoon, Hyonok

    2016-09-15

    The proper functioning of the endoplasmic reticulum (ER) is crucial for multiple cellular activities and survival. Disturbances in the normal ER functions lead to the accumulation and aggregation of unfolded proteins, which initiates an adaptive response, the unfolded protein response (UPR), in order to regain normal ER functions. Failure to activate the adaptive response initiates the process of programmed cell death or apoptosis. Apoptosis plays an important role in cell elimination, which is essential for embryogenesis, development, and tissue homeostasis. Impaired apoptosis can lead to the development of various pathological conditions, such as neurodegenerative and autoimmune diseases, cancer, or acquired immune deficiency syndrome (AIDS). Calcium (Ca(2+)) is one of the key regulators of cell survival and it can induce ER stress-mediated apoptosis in response to various conditions. Ca(2+) regulates cell death both at the early and late stages of apoptosis. Severe Ca(2+) dysregulation can promote cell death through apoptosis. Action potential, an electrical signal transmitted along the neurons and muscle fibers, is important for conveying information to, from, and within the brain. Upon the initiation of the action potential, increased levels of cytosolic Ca(2+) (depolarization) lead to the activation of the ER stress response involved in the initiation of apoptosis. In this review, we discuss the involvement of Ca(2+) and action potential in ER stress-mediated apoptosis.

  3. Determination of Nerve Fiber Diameter Distribution From Compound Action Potential: A Continuous Approach.

    Science.gov (United States)

    Un, M Kerem; Kaghazchi, Hamed

    2018-01-01

    When a signal is initiated in the nerve, it is transmitted along each nerve fiber via an action potential (called single fiber action potential (SFAP)) which travels with a velocity that is related with the diameter of the fiber. The additive superposition of SFAPs constitutes the compound action potential (CAP) of the nerve. The fiber diameter distribution (FDD) in the nerve can be computed from the CAP data by solving an inverse problem. This is usually achieved by dividing the fibers into a finite number of diameter groups and solve a corresponding linear system to optimize FDD. However, number of fibers in a nerve can be measured sometimes in thousands and it is possible to assume a continuous distribution for the fiber diameters which leads to a gradient optimization problem. In this paper, we have evaluated this continuous approach to the solution of the inverse problem. We have utilized an analytical function for SFAP and an assumed a polynomial form for FDD. The inverse problem involves the optimization of polynomial coefficients to obtain the best estimate for the FDD. We have observed that an eighth order polynomial for FDD can capture both unimodal and bimodal fiber distributions present in vivo, even in case of noisy CAP data. The assumed FDD distribution regularizes the ill-conditioned inverse problem and produces good results.

  4. ER Stress-Mediated Signaling: Action Potential and Ca2+ as Key Players

    Science.gov (United States)

    Bahar, Entaz; Kim, Hyongsuk; Yoon, Hyonok

    2016-01-01

    The proper functioning of the endoplasmic reticulum (ER) is crucial for multiple cellular activities and survival. Disturbances in the normal ER functions lead to the accumulation and aggregation of unfolded proteins, which initiates an adaptive response, the unfolded protein response (UPR), in order to regain normal ER functions. Failure to activate the adaptive response initiates the process of programmed cell death or apoptosis. Apoptosis plays an important role in cell elimination, which is essential for embryogenesis, development, and tissue homeostasis. Impaired apoptosis can lead to the development of various pathological conditions, such as neurodegenerative and autoimmune diseases, cancer, or acquired immune deficiency syndrome (AIDS). Calcium (Ca2+) is one of the key regulators of cell survival and it can induce ER stress-mediated apoptosis in response to various conditions. Ca2+ regulates cell death both at the early and late stages of apoptosis. Severe Ca2+ dysregulation can promote cell death through apoptosis. Action potential, an electrical signal transmitted along the neurons and muscle fibers, is important for conveying information to, from, and within the brain. Upon the initiation of the action potential, increased levels of cytosolic Ca2+ (depolarization) lead to the activation of the ER stress response involved in the initiation of apoptosis. In this review, we discuss the involvement of Ca2+ and action potential in ER stress-mediated apoptosis. PMID:27649160

  5. Action potential generation requires a high sodium channel density in the axon initial segment.

    Science.gov (United States)

    Kole, Maarten H P; Ilschner, Susanne U; Kampa, Björn M; Williams, Stephen R; Ruben, Peter C; Stuart, Greg J

    2008-02-01

    The axon initial segment (AIS) is a specialized region in neurons where action potentials are initiated. It is commonly assumed that this process requires a high density of voltage-gated sodium (Na(+)) channels. Paradoxically, the results of patch-clamp studies suggest that the Na(+) channel density at the AIS is similar to that at the soma and proximal dendrites. Here we provide data obtained by antibody staining, whole-cell voltage-clamp and Na(+) imaging, together with modeling, which indicate that the Na(+) channel density at the AIS of cortical pyramidal neurons is approximately 50 times that in the proximal dendrites. Anchoring of Na(+) channels to the cytoskeleton can explain this discrepancy, as disruption of the actin cytoskeleton increased the Na(+) current measured in patches from the AIS. Computational models required a high Na(+) channel density (approximately 2,500 pS microm(-2)) at the AIS to account for observations on action potential generation and backpropagation. In conclusion, action potential generation requires a high Na(+) channel density at the AIS, which is maintained by tight anchoring to the actin cytoskeleton.

  6. Low Somatic Sodium Conductance Enhances Action Potential Precision in Time-Coding Auditory Neurons.

    Science.gov (United States)

    Yang, Yang; Ramamurthy, Bina; Neef, Andreas; Xu-Friedman, Matthew A

    2016-11-23

    Auditory nerve fibers encode sounds in the precise timing of action potentials (APs), which is used for such computations as sound localization. Timing information is relayed through several cell types in the auditory brainstem that share an unusual property: their APs are not overshooting, suggesting that the cells have very low somatic sodium conductance (gNa). However, it is not clear how gNa influences temporal precision. We addressed this by comparing bushy cells (BCs) in the mouse cochlear nucleus with T-stellate cells (SCs), which do have normal overshooting APs. BCs play a central role in both relaying and refining precise timing information from the auditory nerve, whereas SCs discard precise timing information and encode the envelope of sound amplitude. Nucleated-patch recording at near-physiological temperature indicated that the Na current density was 62% lower in BCs, and the voltage dependence of gNa inactivation was 13 mV hyperpolarized compared with SCs. We endowed BCs with SC-like gNa using two-electrode dynamic clamp and found that synaptic activity at physiologically relevant rates elicited APs with significantly lower probability, through increased activation of delayed rectifier channels. In addition, for two near-simultaneous synaptic inputs, the window of coincidence detection widened significantly with increasing gNa, indicating that refinement of temporal information by BCs is degraded by gNa Thus, reduced somatic gNa appears to be an adaption for enhancing fidelity and precision in time-coding neurons. Proper hearing depends on analyzing temporal aspects of sounds with high precision. Auditory neurons that specialize in precise temporal information have a suite of unusual intrinsic properties, including nonovershooting action potentials and few sodium channels in the soma. However, it was not clear how low sodium channel availability in the soma influenced the temporal precision of action potentials initiated in the axon initial segment

  7. Regulation of gap junction conductance by calcineurin through Cx43 phosphorylation: implications for action potential conduction.

    Science.gov (United States)

    Jabr, Rita I; Hatch, Fiona S; Salvage, Samantha C; Orlowski, Alejandro; Lampe, Paul D; Fry, Christopher H

    2016-11-01

    Cardiac arrhythmias are associated with raised intracellular [Ca 2+ ] and slowed action potential conduction caused by reduced gap junction (GJ) electrical conductance (Gj). Ventricular GJs are composed of connexin proteins (Cx43), with Gj determined by Cx43 phosphorylation status. Connexin phosphorylation is an interplay between protein kinases and phosphatases but the precise pathways are unknown. We aimed to identify key Ca 2+ -dependent phosphorylation sites on Cx43 that regulate cardiac gap junction conductance and action potential conduction velocity. We investigated the role of the Ca 2+ -dependent phosphatase, calcineurin. Intracellular [Ca 2+ ] was raised in guinea-pig myocardium by a low-Na solution or increased stimulation. Conduction velocity and Gj were measured in multicellular strips. Phosphorylation of Cx43 serine residues (S365 and S368) and of the intermediary regulator I1 at threonine35 was measured by Western blot. Measurements were made in the presence and absence of inhibitors to calcineurin, I1 or protein phosphatase-1 and phosphatase-2.Raised [Ca 2 + ] i decreased Gj, reduced Cx43 phosphorylation at S365 and increased it at S368; these changes were reversed by calcineurin inhibitors. Cx43-S368 phosphorylation was reversed by the protein kinase C inhibitor chelerythrine. Raised [Ca 2+ ] i also decreased I1 phosphorylation, also prevented by calcineurin inhibitors, to increase activity of the Ca 2+ -independent phosphatase, PPI. The PP1 inhibitor, tautomycin, prevented Cx43-365 dephosphorylation, Cx43-S368 phosphorylation and Gj reduction in raised [Ca 2+ ] i . PP2A had no role. Conduction velocity was reduced by raised [Ca 2+ ] i and reversed by calcineurin inhibitors. Reduced action potential conduction and Gj in raised [Ca 2+ ] are regulated by calcineurin-dependent Cx43-S365 phosphorylation, leading to Cx43-S368 dephosphorylation. The calcineurin action is indirect, via I1 dephosphorylation and subsequent activation of PP1.

  8. Environmental Asthma Reduction Potential Estimates for Selected Mitigation Actions in Finland Using a Life Table Approach

    Directory of Open Access Journals (Sweden)

    Isabell Katharina Rumrich

    2015-06-01

    Full Text Available Aims: To quantify the reduction potential of asthma in Finland achievable by adjusting exposures to selected environmental factors. Methods: A life table model for the Finnish population for 1986–2040 was developed and Years Lived with Disability caused by asthma and attributable to the following selected exposures were estimated: tobacco smoke (smoking and second hand tobacco smoke, ambient fine particles, indoor dampness and mould, and pets. Results: At baseline (2011 about 25% of the total asthma burden was attributable to the selected exposures. Banning tobacco was the most efficient mitigation action, leading to 6% reduction of the asthma burden. A 50% reduction in exposure to dampness and mould as well as a doubling in exposure to pets lead each to a 2% reduction. Ban of urban small scale wood combustion, chosen as a mitigation action to reduce exposure to fine particles, leads to a reduction of less than 1% of the total asthma burden. Combination of the most efficient mitigation actions reduces the total asthma burden by 10%. A more feasible combination of mitigation actions leads to 6% reduction of the asthma burden. Conclusions: The adjustment of environmental exposures can reduce the asthma burden in Finland by up to 10%.

  9. Event-related potential effects of superior action anticipation in professional badminton players.

    Science.gov (United States)

    Jin, Hua; Xu, Guiping; Zhang, John X; Gao, Hongwei; Ye, Zuoer; Wang, Pin; Lin, Huiyan; Mo, Lei; Lin, Chong-De

    2011-04-04

    The ability to predict the trajectory of a ball based on the opponent's body kinematics has been shown to be critical to high-performing athletes in many sports. However, little is known about the neural correlates underlying such superior ability in action anticipation. The present event-related potential study compared brain responses from professional badminton players and non-player controls when they watched video clips of badminton games and predicted a ball's landing position. Replicating literature findings, the players made significantly more accurate judgments than the controls and showed better action anticipation. Correspondingly, they showed enlarged amplitudes of two ERP components, a P300 peaking around 350ms post-stimulus with a parietal scalp distribution and a P2 peaking around 250ms with a posterior-occipital distribution. The P300 effect was interpreted to reflect primed access and/or directing of attention to game-related memory representations in the players facilitating their online judgment of related actions. The P2 effect was suggested to reflect some generic learning effects. The results identify clear neural responses that differentiate between different levels of action anticipation associated with sports expertise. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  10. Action Research’s Potential to Foster Institutional Change for Urban Water Management

    Directory of Open Access Journals (Sweden)

    Dimitrios Zikos

    2013-04-01

    Full Text Available The paper discusses the potential of action research to meet the challenges entailed in institutional design for urban water management. Our overall aim is to briefly present action research and discuss its methodological merits with regard to the challenges posed by the different conceptual bases for extrapolating the effects of institutional design on institutional change. Thus, our aim is to explore how Action Research meets the challenge of scoping the field in an open fashion for determining the appropriate mechanisms of institutional change and supporting the emerging of new water institutions. To accomplish this aim, we select the Water Framework Directive (WFD as an illustrative driving force requiring changes in water management practices and implying the need for the emergence of new institutions. We employ a case of urban water management in the Volos Metropolitan Area, part of the Thessaly region in Greece, where a Pilot River Basin Plan was implemented. By applying action research and being involved in a long process of interaction between stakeholders, we examine the emergence of new institutions dealing with urban water management under the general principles of the major driving force for change: the WFD.

  11. Parameters of a cylindrical Woods-Saxon potential for the rare-earth region

    Energy Technology Data Exchange (ETDEWEB)

    Nojarov, R.

    1984-04-01

    A connection is established between the parameters of two widely used realisations of the deformed axially symmetric Woods-Saxon potential - the spherical coordinates Dubna version and the cylindrical coordinates Copenhagen version. The parameters of the latter version version are determined for the mass zones A = 155, 165, 173 and 181 by a fit to the single-particle levels of the former version but a larger nuclear radius (rsup(n)/sub 0/=1.30 fm, rsup(p)/sub 0/=1.28 fm) is introduced in order to better reproduce the experimental RMS radii.

  12. Contaminant Transport Parameters for the Groundwater Flow and Contaminant Transport Model of Corrective Action Units 101 and 102: Central and Western Pahute Mesa, Nye County, Nevada, Revision 0

    Energy Technology Data Exchange (ETDEWEB)

    Drici, Warda [International Technologies Corporation, Las Vegas, NV (United States)

    2003-08-01

    This report documents the analysis of the available transport parameter data conducted in support of the development of a Corrective Action Unit (CAU) groundwater flow model for Central and Western Pahute Mesa: CAUs 101 and 102.

  13. The real-time link between person perception and action: brain potential evidence for dynamic continuity.

    Science.gov (United States)

    Freeman, Jonathan B; Ambady, Nalini; Midgley, Katherine J; Holcomb, Phillip J

    2011-01-01

    Using event-related potentials, we investigated how the brain extracts information from another's face and translates it into relevant action in real time. In Study 1, participants made between-hand sex categorizations of sex-typical and sex-atypical faces. Sex-atypical faces evoked negativity between 250 and 550 ms (N300/N400 effects), reflecting the integration of accumulating sex-category knowledge into a coherent sex-category interpretation. Additionally, the lateralized readiness potential revealed that the motor cortex began preparing for a correct hand response while social category knowledge was still gradually evolving in parallel. In Study 2, participants made between-hand eye-color categorizations as part of go/no-go trials that were contingent on a target's sex. On no-go trials, although the hand did not actually move, information about eye color partially prepared the motor cortex to move the hand before perception of sex had finalized. Together, these findings demonstrate the dynamic continuity between person perception and action, such that ongoing results from face processing are immediately and continuously cascaded into the motor system over time. The preparation of action begins based on tentative perceptions of another's face before perceivers have finished interpreting what they just saw. © 2010 Psychology Press, an imprint of the Taylor & Francis Group, an Informa business

  14. Assessing the Potential of Climate Change Mitigation Actions in Three Different City Types in Finland

    Directory of Open Access Journals (Sweden)

    Seppo Junnila

    2012-07-01

    Full Text Available As the effects of global warming have become more evident, ambitious short-term greenhouse gas emission reduction targets have been set in recent years. Many cities worldwide have adopted an active approach to climate change mitigation, but policy makers are not always knowledgeable of the true effects of their planned mitigation action. The purpose of this paper is to evaluate the effectiveness of different mitigation strategies in achieving low-carbon urban communities. The assessment is conducted via means of consumption based hybrid life-cycle assessment, which allows the reduction potential to be analyzed from the perspective of an individual resident of the urban community. The assessed actions represent strategies that are both adopted by the case cities and possible to implement with current best practices in Finland. The four assessed actions comprise: (1 dense urban structure with less private driving; (2 the use of energy production based on renewable sources; (3 new low-energy residential construction; and (4 improving the energy efficiency of existing buildings. The findings show that the effectiveness depends greatly on the type of city, although in absolute terms the most significant reduction potential lies with lowering the fossil fuel dependence of the local energy production.

  15. Field and action potential recordings in heart slices: correlation with established in vitro and in vivo models

    Science.gov (United States)

    Himmel, Herbert M; Bussek, Alexandra; Hoffmann, Michael; Beckmann, Rolf; Lohmann, Horst; Schmidt, Matthias; Wettwer, Erich

    2012-01-01

    BACKGROUND AND PURPOSE Action potential (AP) recordings in ex vivo heart preparations constitute an important component of the preclinical cardiac safety assessment according to the ICH S7B guideline. Most AP measurement models are sensitive, predictive and informative but suffer from a low throughput. Here, effects of selected anti-arrhythmics (flecainide, quinidine, atenolol, sotalol, dofetilide, nifedipine, verapamil) on field/action potentials (FP/AP) of guinea pig and rabbit ventricular slices are presented and compared with data from established in vitro and in vivo models. EXPERIMENTAL APPROACH Data from measurements of membrane currents (hERG, INa), AP/FP (guinea pig and rabbit ventricular slices), AP (rabbit Purkinje fibre), haemodynamic/ECG parameters (conscious, telemetered dog) were collected, compared and correlated to complementary published data (focused literature search). KEY RESULTS The selected anti-arrhythmics, flecainide, quinidine, atenolol, sotalol, dofetilide, nifedipine and verapamil, influenced the shape of AP/FP of guinea pig and rabbit ventricular slices in a manner similar to that observed for rabbit PF. The findings obtained from slice preparations are in line with measurements of membrane currents in vitro, papillary muscle AP in vitro and haemodynamic/ECG parameters from conscious dogs in vivo, and were also corroborated by published data. CONCLUSION AND IMPLICATIONS FP and AP recordings from heart slices correlated well with established in vitro and in vivo models in terms of pharmacology and predictability. Heart slice preparations yield similar results as papillary muscle but offer enhanced throughput for mechanistic investigations and may substantially reduce the use of laboratory animals. PMID:22074238

  16. Voltage-gated sodium channel expression and action potential generation in differentiated NG108-15 cells.

    Science.gov (United States)

    Liu, Jinxu; Tu, Huiyin; Zhang, Dongze; Zheng, Hong; Li, Yu-Long

    2012-10-25

    The generation of action potential is required for stimulus-evoked neurotransmitter release in most neurons. Although various voltage-gated ion channels are involved in action potential production, the initiation of the action potential is mainly mediated by voltage-gated Na+ channels. In the present study, differentiation-induced changes of mRNA and protein expression of Na+ channels, Na+ currents, and cell membrane excitability were investigated in NG108-15 cells. Whole-cell patch-clamp results showed that differentiation (9 days) didn't change cell membrane excitability, compared to undifferentiated state. But differentiation (21 days) induced the action potential generation in 45.5% of NG108-15 cells (25/55 cells). In 9-day-differentiated cells, Na+ currents were mildly increased, which was also found in 21-day differentiated cells without action potential. In 21-day differentiated cells with action potential, Na+ currents were significantly enhanced. Western blot data showed that the expression of Na+ channels was increased with differentiated-time dependent manner. Single-cell real-time PCR data demonstrated that the expression of Na+ channel mRNA was increased by 21 days of differentiation in NG108-15 cells. More importantly, the mRNA level of Na+ channels in cells with action potential was higher than that in cells without action potential. Differentiation induces expression of voltage-gated Na+ channels and action potential generation in NG108-15 cells. A high level of the Na+ channel density is required for differentiation-triggered action potential generation.

  17. Associates of mortality and hospitalization in hemodialysis: potentially actionable laboratory variables and vascular access.

    Science.gov (United States)

    Lacson, Eduardo; Wang, Weiling; Hakim, Raymond M; Teng, Ming; Lazarus, J Michael

    2009-01-01

    To determine the most significant potentially actionable clinical variables associated with mortality and hospitalization risk in hemodialysis (HD) patients. Cohort study. Adult maintenance HD patients in the Fresenius Medical Care, North America database as of January 1, 2004, with baseline information from October 1, 2003, to December 31, 2003, comprising approximately 26% of the US HD population. Case-mix (age, sex, race, diabetes, vintage, and body surface area), vascular access, and laboratory (albumin, equilibrated Kt/V, hemoglobin, calcium, phosphorus, creatinine, bicarbonate, biointact parathyroid hormone, transferrin saturation, and white blood cell count) variables. 1-year mortality and hospitalization risk from January 1 to December 31, 2004. Cox proportional hazards models for death and hospitalization. The cohort (N = 78,420) had a mean age of 61.4 +/- 15.0 years, 47% were women, 49% were white, 41% were black race (10% defined as "other"), and 52% had diabetes. The top 5 actionable variables were the same for mortality and hospitalization. Final case-mix plus laboratory-adjusted hazard ratios for these top 5 actionable variables indicate 177% increased risk of death and 67% increased risk of hospitalization per 1-g/dL decrease in albumin level, 39% and 45% greater risk with catheters compared with fistulas, 18% and 9% greater risk per 1-mg/dL greater phosphorus level, 11% and 9% lower risk per 1-g/dL greater hemoglobin level, and 5% and 2% greater risk per 0.1-unit decrease in equilibrated Kt/V, respectively (all P < 0.0001). Observational cross-sectional study with limited comorbidity adjustment (for diabetes). The same variables are associated with both mortality and hospitalization in HD patients. The top 5 potentially actionable variables are readily identifiable, with albumin level and catheter use the most prominent, and all 5 are appropriate targets for improvement.

  18. Escape time from potential wells of strongly nonlinear oscillators with slowly varying parameters

    Directory of Open Access Journals (Sweden)

    Cai Jianping

    2005-01-01

    Full Text Available The effect of negative damping to an oscillatory system is to force the amplitude to increase gradually and the motion will be out of the potential well of the oscillatory system eventually. In order to deduce the escape time from the potential well of quadratic or cubic nonlinear oscillator, the multiple scales method is firstly used to obtain the asymptotic solutions of strongly nonlinear oscillators with slowly varying parameters, and secondly the character of modulus of Jacobian elliptic function is applied to derive the equations governing the escape time. The approximate potential method, instead of Taylor series expansion, is used to approximate the potential of an oscillation system such that the asymptotic solution can be expressed in terms of Jacobian elliptic function. Numerical examples verify the efficiency of the present method.

  19. Sodium and potassium currents involved in action potential propagation in normal bovine lactotrophs.

    Science.gov (United States)

    Cobbett, P; Ingram, C D; Mason, W T

    1987-11-01

    1. The properties of whole-cell and single-channel Na+ and K+ currents in immunocytochemically identified bovine lactotrophs were studied using the patch-clamp technique. 2. In the whole-cell, current-clamp mode, cells had membrane potentials of -94.7 +/- 6.7 mV and input resistances of 2-17 G omega. Current-induced action potentials were recorded with a threshold around -35 mV and amplitude of 40-65 mV. Repetitive firing was not sustained at frequencies greater than 1-2 Hz without total inactivation. 3. Under voltage clamp, action potentials were shown to be composed of an inward TTX-sensitive Na+ current and an outward K+ current that was abolished by internal Cs+. 4. The isolated Na+ current had a threshold for activation around -35 mV and rapidly inactivated to a steady state during a test voltage pulse. Inactivation was strongly voltage-dependent, with the Na+ current being half-inactivated at -20 mV. 5. Recovery from inactivation was voltage dependent and at a holding potential of -60 mV, 50% reactivation was achieved after 420 ms. The implications of this long reactivation time on sustained action potential frequency are discussed. 6. Single Na+ channel activity was examined with the outside-out patch configuration and yielded single-channel conductances of 22.5 pS. Reconstruction of the voltage and time dependence of single-channel currents provided an accurate picture of the whole-cell Na+ current. 7. Whole-cell outward current carried by K+ in the absence of Na+ and Ca2+ had a large conductance, was slowly activated and demonstrated no inactivation. A second, more rapidly activating Ca2+-dependent K+ current could also be demonstrated. 8. Ensemble analysis of whole-cell K+ currents in the absence of Ca2+ showed underlying single-channel amplitudes of 1.2 pA at +10 mV, with the lactotroph having about 350 active channels at this potential. 9. Recordings of single K+ channels also demonstrated two classes of channel: a small (50 pS) voltage

  20. Selecting the smoothing parameter for estimation of slowly changing evoked potential signals.

    Science.gov (United States)

    Raz, J; Turetsky, B; Fein, G

    1989-09-01

    Brain evoked potential (EP) data consist of a true response ("signal") and random background activity ("noise"), which are observed over repeated stimulus presentations ("trials"). A signal that changes slowly from trial to trial can be estimated by smoothing across trials and over time within trials. We present a method for selecting the smoothing parameter by minimizing an estimate of the mean average squared error (MASE). We evaluate the performance of this method using simulated EP data, and apply the method to an example set of real flash evoked potentials.

  1. An Excel‐based implementation of the spectral method of action potential alternans analysis

    Science.gov (United States)

    Pearman, Charles M.

    2014-01-01

    Abstract Action potential (AP) alternans has been well established as a mechanism of arrhythmogenesis and sudden cardiac death. Proper interpretation of AP alternans requires a robust method of alternans quantification. Traditional methods of alternans analysis neglect higher order periodicities that may have greater pro‐arrhythmic potential than classical 2:1 alternans. The spectral method of alternans analysis, already widely used in the related study of microvolt T‐wave alternans, has also been used to study AP alternans. Software to meet the specific needs of AP alternans analysis is not currently available in the public domain. An AP analysis tool is implemented here, written in Visual Basic for Applications and using Microsoft Excel as a shell. This performs a sophisticated analysis of alternans behavior allowing reliable distinction of alternans from random fluctuations, quantification of alternans magnitude, and identification of which phases of the AP are most affected. In addition, the spectral method has been adapted to allow detection and quantification of higher order regular oscillations. Analysis of action potential morphology is also performed. A simple user interface enables easy import, analysis, and export of collated results. PMID:25501439

  2. An Excel-based implementation of the spectral method of action potential alternans analysis.

    Science.gov (United States)

    Pearman, Charles M

    2014-12-01

    Action potential (AP) alternans has been well established as a mechanism of arrhythmogenesis and sudden cardiac death. Proper interpretation of AP alternans requires a robust method of alternans quantification. Traditional methods of alternans analysis neglect higher order periodicities that may have greater pro-arrhythmic potential than classical 2:1 alternans. The spectral method of alternans analysis, already widely used in the related study of microvolt T-wave alternans, has also been used to study AP alternans. Software to meet the specific needs of AP alternans analysis is not currently available in the public domain. An AP analysis tool is implemented here, written in Visual Basic for Applications and using Microsoft Excel as a shell. This performs a sophisticated analysis of alternans behavior allowing reliable distinction of alternans from random fluctuations, quantification of alternans magnitude, and identification of which phases of the AP are most affected. In addition, the spectral method has been adapted to allow detection and quantification of higher order regular oscillations. Analysis of action potential morphology is also performed. A simple user interface enables easy import, analysis, and export of collated results. © 2014 The Author. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  3. Beat-to-beat variability of cardiac action potential duration: underlying mechanism and clinical implications.

    Science.gov (United States)

    Nánási, Péter P; Magyar, János; Varró, András; Ördög, Balázs

    2017-10-01

    Beat-to-beat variability of cardiac action potential duration (short-term variability, SV) is a common feature of various cardiac preparations, including the human heart. Although it is believed to be one of the best arrhythmia predictors, the underlying mechanisms are not fully understood at present. The magnitude of SV is basically determined by the intensity of cell-to-cell coupling in multicellular preparations and by the duration of the action potential (APD). To compensate for the APD-dependent nature of SV, the concept of relative SV (RSV) has been introduced by normalizing the changes of SV to the concomitant changes in APD. RSV is reduced by I Ca , I Kr , and I Ks while increased by I Na , suggesting that ion currents involved in the negative feedback regulation of APD tend to keep RSV at a low level. RSV is also influenced by intracellular calcium concentration and tissue redox potential. The clinical implications of APD variability is discussed in detail.

  4. Carbon monoxide effects on human ventricle action potential assessed by mathematical simulations.

    Science.gov (United States)

    Trenor, Beatriz; Cardona, Karen; Saiz, Javier; Rajamani, Sridharan; Belardinelli, Luiz; Giles, Wayne R

    2013-01-01

    Carbon monoxide (CO) that is produced in a number of different mammalian tissues is now known to have significant effects on the cardiovascular system. These include: (i) vasodilation, (ii) changes in heart rate and strength of contractions, and (iii) modulation of autonomic nervous system input to both the primary pacemaker and the working myocardium. Excessive CO in the environment is toxic and can initiate or mediate life threatening cardiac rhythm disturbances. Recent reports link these ventricular arrhythmias to an increase in the slowly inactivating, or "late" component of the Na(+) current in the mammalian heart. The main goal of this paper is to explore the basis of this pro-arrhythmic capability of CO by incorporating changes in CO-induced ion channel activity with intracellular signaling pathways in the mammalian heart. To do this, a quite well-documented mathematical model of the action potential and intracellular calcium transient in the human ventricular myocyte has been employed. In silico iterations based on this model provide a useful first step in illustrating the cellular electrophysiological consequences of CO that have been reported from mammalian heart experiments. Specifically, when the Grandi et al. model of the human ventricular action potential is utilized, and after the Na(+) and Ca(2+) currents in a single myocyte are modified based on the experimental literature, early after-depolarization (EAD) rhythm disturbances appear, and important elements of the underlying causes of these EADs are revealed/illustrated. Our modified mathematical model of the human ventricular action potential also provides a convenient digital platform for designing future experimental work and relating these changes in cellular cardiac electrophysiology to emerging clinical and epidemiological data on CO toxicity.

  5. On modelling of physical effects accompanying the propagation of action potentials in nerve fibres

    CERN Document Server

    Engelbrecht, Jüri; Tamm, Kert; Laasmaa, Martin; Vendelin, Marko

    2016-01-01

    The recent theoretical and experimental studies have revealed many details of signal propagation in nervous systems. In this paper an attempt is made to unify various mathematical models which describe the signal propagation in nerve fibres. The analysis of existing single models permits to select the leading physiological effects. As a result, a more general mathematical model is described based on the coupling of action potentials with mechanical waves in a nerve fibre. The crucial issue is how to model coupling effects which are strongly linked to the ion currents through biomembranes.

  6. New parameter-free polarization potentials in low-energy positron collisions

    Science.gov (United States)

    Jain, Ashok

    1990-01-01

    The polarization potential plays a decisive role in shaping up the cross sections in low energy positron collisions with atoms and molecules. However, its inclusion without involving any adjustable parameter, is still a challenge. Various other techniques employed so far for positron collisions are summarized, and a new, nonadjustable and very simple form of the polarization potential for positron-atom (molecule) collisions below the threshold of positronium formation is discussed. This new recently proposed potential is based on the correlation energy of a single positron in a homogeneous electron gas. The correlation energy was calculated by solving the Schrodinger equation of the positron-electron system and fitted to an analytical form in various ranges of the density parameter. In the outside region, the correlation energy is joined smoothly with the correct asymptotic form. This new positron correlation polarization (PCOP) potential was tested on several atomic and molecular targets such as the Ar, CO, and CH4. The results on the total and differential cross sections on these targets are shown along with the experimental data where available.

  7. Three-dimensional mapping and regulation of action potential propagation in nanoelectronics-innervated tissues.

    Science.gov (United States)

    Dai, Xiaochuan; Zhou, Wei; Gao, Teng; Liu, Jia; Lieber, Charles M

    2016-09-01

    Real-time mapping and manipulation of electrophysiology in three-dimensional (3D) tissues could have important impacts on fundamental scientific and clinical studies, yet realization is hampered by a lack of effective methods. Here we introduce tissue-scaffold-mimicking 3D nanoelectronic arrays consisting of 64 addressable devices with subcellular dimensions and a submillisecond temporal resolution. Real-time extracellular action potential (AP) recordings reveal quantitative maps of AP propagation in 3D cardiac tissues, enable in situ tracing of the evolving topology of 3D conducting pathways in developing cardiac tissues and probe the dynamics of AP conduction characteristics in a transient arrhythmia disease model and subsequent tissue self-adaptation. We further demonstrate simultaneous multisite stimulation and mapping to actively manipulate the frequency and direction of AP propagation. These results establish new methodologies for 3D spatiotemporal tissue recording and control, and demonstrate the potential to impact regenerative medicine, pharmacology and electronic therapeutics.

  8. Three-dimensional mapping and regulation of action potential propagation in nanoelectronics innervated tissues

    Science.gov (United States)

    Dai, Xiaochuan; Zhou, Wei; Gao, Teng; Liu, Jia; Lieber, Charles M.

    2016-01-01

    Real-time mapping and manipulation of electrophysiology in three-dimensional (3D) tissues could impact broadly fundamental scientific and clinical studies, yet realization lacks effective methods. Here we introduce tissue-scaffold-mimicking 3D nanoelectronic arrays consisting of 64 addressable devices with subcellular dimensions and sub-millisecond time-resolution. Real-time extracellular action potential (AP) recordings reveal quantitative maps of AP propagation in 3D cardiac tissues, enable in situ tracing of the evolving topology of 3D conducting pathways in developing cardiac tissues, and probe the dynamics of AP conduction characteristics in a transient arrhythmia disease model and subsequent tissue self-adaptation. We further demonstrate simultaneous multi-site stimulation and mapping to manipulate actively the frequency and direction of AP propagation. These results establish new methodologies for 3D spatiotemporal tissue recording and control, and demonstrate the potential to impact regenerative medicine, pharmacology and electronic therapeutics. PMID:27347837

  9. Double peak sensory nerve action potentials to single stimuli in nerve conduction studies.

    Science.gov (United States)

    Leote, Joao; Pereira, Pedro; Valls-Sole, Josep

    2017-05-01

    In humans, sensory nerve action potentials (SNAPs) can show 2 separate deflections, i.e., double peak potentials (DPp), which necessarily means that 1 peak is delayed with respect to the other. DPps may have various origins and be due to either physical or physiological properties. We review the nature of commonly encountered DPps in clinical practice, provide the most likely interpretations for their physiological origin, and assess their reproducibility and clinical utility. We classified the DPps into 3 categories: (1) simultaneous anodal and cathodal stimulation. (2) simultaneous recording from 2 different nerves at the same site, and (3) SNAP desynchronization. Although the recording of DPps is not a standardized neurophysiological method, their study brings interesting cues about the physiology of nerve stimulation and paves the way for clinical application of such an observation. Muscle Nerve 55: 619-625, 2017. © 2016 Wiley Periodicals, Inc.

  10. Black hole algorithm for determining model parameter in self-potential data

    Science.gov (United States)

    Sungkono; Warnana, Dwa Desa

    2018-01-01

    Analysis of self-potential (SP) data is increasingly popular in geophysical method due to its relevance in many cases. However, the inversion of SP data is often highly nonlinear. Consequently, local search algorithms commonly based on gradient approaches have often failed to find the global optimum solution in nonlinear problems. Black hole algorithm (BHA) was proposed as a solution to such problems. As the name suggests, the algorithm was constructed based on the black hole phenomena. This paper investigates the application of BHA to solve inversions of field and synthetic self-potential (SP) data. The inversion results show that BHA accurately determines model parameters and model uncertainty. This indicates that BHA is highly potential as an innovative approach for SP data inversion.

  11. The Relation Between Adult Dark Spermatogonia and Other Parameters of Fertility Potential in Cryptorchid Testes

    DEFF Research Database (Denmark)

    Thorup, Jørgen Mogens; Kvist, Kolja; Clasen-Linde, Erik

    2013-01-01

    The fertility potential of boys with cryptorchidism may be related to the number of adult dark spermatogonia per tubular transverse section in testicular biopsies taken at orchiopexy. Placental-like alkaline phosphatase positive gonocytes in testes within year 1 of life indicate preserved ability...... for germ cell transformation. We related these parameters to the total number of tubular germ cells and other factors associated with fertility potential.......The fertility potential of boys with cryptorchidism may be related to the number of adult dark spermatogonia per tubular transverse section in testicular biopsies taken at orchiopexy. Placental-like alkaline phosphatase positive gonocytes in testes within year 1 of life indicate preserved ability...

  12. RIM-BPs Mediate Tight Coupling of Action Potentials to Ca(2+)-Triggered Neurotransmitter Release.

    Science.gov (United States)

    Acuna, Claudio; Liu, Xinran; Gonzalez, Aneysis; Südhof, Thomas C

    2015-09-23

    Ultrafast neurotransmitter release requires tight colocalization of voltage-gated Ca(2+) channels with primed, release-ready synaptic vesicles at the presynaptic active zone. RIM-binding proteins (RIM-BPs) are multidomain active zone proteins that bind to RIMs and to Ca(2+) channels. In Drosophila, deletion of RIM-BPs dramatically reduces neurotransmitter release, but little is known about RIM-BP function in mammalian synapses. Here, we generated double conditional knockout mice for RIM-BP1 and RIM-BP2, and analyzed RIM-BP-deficient synapses in cultured hippocampal neurons and the calyx of Held. Surprisingly, we find that in murine synapses, RIM-BPs are not essential for neurotransmitter release as such, but are selectively required for high-fidelity coupling of action potential-induced Ca(2+) influx to Ca(2+)-stimulated synaptic vesicle exocytosis. Deletion of RIM-BPs decelerated action-potential-triggered neurotransmitter release and rendered it unreliable, thereby impairing the fidelity of synaptic transmission. Thus, RIM-BPs ensure optimal organization of the machinery for fast release in mammalian synapses without being a central component of the machinery itself. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. The linear synchronization measures of uterine EMG signals: Evidence of synchronized action potentials during propagation.

    Science.gov (United States)

    Domino, Malgorzata; Pawlinski, Bartosz; Gajewski, Zdzislaw

    2016-11-01

    Evaluation of synchronization between myoelectric signals can give new insights into the functioning of the complex system of porcine myometrium. We propose a model of uterine contractions according to the hypothesis of action potentials similarity which is possible to detect during propagation in the uterine wall. We introduce similarity measures based on the concept of synchronization as used in matching linear signals such as electromyographic (EMG) time series data. The aim was to present linear measures to assess synchronization between contractions in different topographic regions of the uterus. We use the cross-correlation function (ƒx,y[l], ƒy,z[l]) and the cross-coherence function (Cxy[ƒ], Cyz[ƒ]) to assess synchronization between three data series of a diestral uterine EMG bundles in porcine reproductive tract. Spontaneous uterine activity was recorded using telemetry method directly by three-channel transmitter and three silver bipolar needle electrodes sutured on different topographic regions of the reproductive tract in the sow. The results show the usefulness of the cross-coherence function in that synchronization between uterine horn and corpus uteri for multiple action potentials (bundles) could be observed. The EMG bundles synchronization may be used to investigate the direction and velocity of EMG signals propagation in porcine reproductive tract. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Electrophysiological properties of computational human ventricular cell action potential models under acute ischemic conditions.

    Science.gov (United States)

    Dutta, Sara; Mincholé, Ana; Quinn, T Alexander; Rodriguez, Blanca

    2017-10-01

    Acute myocardial ischemia is one of the main causes of sudden cardiac death. The mechanisms have been investigated primarily in experimental and computational studies using different animal species, but human studies remain scarce. In this study, we assess the ability of four human ventricular action potential models (ten Tusscher and Panfilov, 2006; Grandi et al., 2010; Carro et al., 2011; O'Hara et al., 2011) to simulate key electrophysiological consequences of acute myocardial ischemia in single cell and tissue simulations. We specifically focus on evaluating the effect of extracellular potassium concentration and activation of the ATP-sensitive inward-rectifying potassium current on action potential duration, post-repolarization refractoriness, and conduction velocity, as the most critical factors in determining reentry vulnerability during ischemia. Our results show that the Grandi and O'Hara models required modifications to reproduce expected ischemic changes, specifically modifying the intracellular potassium concentration in the Grandi model and the sodium current in the O'Hara model. With these modifications, the four human ventricular cell AP models analyzed in this study reproduce the electrophysiological alterations in repolarization, refractoriness, and conduction velocity caused by acute myocardial ischemia. However, quantitative differences are observed between the models and overall, the ten Tusscher and modified O'Hara models show closest agreement to experimental data. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. The Influence of Glutamate on Axonal Compound Action Potential In Vitro.

    Science.gov (United States)

    Abouelela, Ahmed; Wieraszko, Andrzej

    2016-01-01

    Background  Our previous experiments demonstrated modulation of the amplitude of the axonal compound action potential (CAP) by electrical stimulation. To verify assumption that glutamate released from axons could be involved in this phenomenon, the modification of the axonal CAP induced by glutamate was investigated. Objectives  The major objective of this research is to verify the hypothesis that axonal activity would trigger the release of glutamate, which in turn would interact with specific axonal receptors modifying the amplitude of the action potential. Methods  Segments of the sciatic nerve were exposed to exogenous glutamate in vitro, and CAP was recorded before and after glutamate application. In some experiments, the release of radioactive glutamate analog from the sciatic nerve exposed to exogenous glutamate was also evaluated. Results  The glutamate-induced increase in CAP was blocked by different glutamate receptor antagonists. The effect of glutamate was not observed in Ca-free medium, and was blocked by antagonists of calcium channels. Exogenous glutamate, applied to the segments of sciatic nerve, induced the release of radioactive glutamate analog, demonstrating glutamate-induced glutamate release. Immunohistochemical examination revealed that axolemma contains components necessary for glutamatergic neurotransmission. Conclusion  The proteins of the axonal membrane can under the influence of electrical stimulation or exogenous glutamate change membrane permeability and ionic conductance, leading to a change in the amplitude of CAP. We suggest that increased axonal activity leads to the release of glutamate that results in changes in the amplitude of CAPs.

  16. Evolution of Action Potential Alternans in Rabbit Heart during Acute Regional Ischemia

    Directory of Open Access Journals (Sweden)

    Irma Martišienė

    2015-01-01

    Full Text Available This study investigates the development of the spatiotemporal pattern of action potential alternans during acute regional ischemia. Experiments were carried out in isolated Langendorff-perfused rabbit heart using a combination of optical mapping and microelectrode recordings. The alternans pattern significantly changed over time and had a biphasic character reaching maximum at 6–9 min after occlusion. Phase I (3–11 minutes of ischemia is characterized by rapid increase in the alternans magnitude and expansion of the alternans territory. Phase I is followed by gradual decline of alternans (Phase II in both magnitude and territory. During both phases we observed significant beat-to-beat variations of the optical action potential amplitude (OAPA alternans. Simultaneous microelectrode recordings from subepicardial and subendocardial layers showed that OAPA alternans coincided with intramural 2 : 1 conduction blocks. Our findings are consistent with the modeling studies predicting that during acute regional ischemia alternans can be driven by 2 : 1 conduction blocks in the ischemic region.

  17. Coupling parameter series expansion for fluid with square-well plus repulsive-square-barrier potential

    Directory of Open Access Journals (Sweden)

    Shiqi Zhou

    2013-10-01

    Full Text Available Monte Carlo simulations in the canonical ensemble are performed for fluid with potential consisting of a square-well plus a square-barrier to obtain thermodynamic properties such as pressure, excess energy, constant volume excess heat capacity, and excess chemical potential, and structural property such as radial distribution function. The simulations cover a wide density range for the fluid phase, several temperatures, and different combinations of the parameters defining the potential. These simulation data have been used to test performances of a coupling parameter series expansion (CPSE recently proposed by one of the authors [S. Zhou, Phys. Rev. E 74, 031119 (2006], and a traditional 2nd-order high temperature series expansion (HTSE based on a macroscopic compressibility approximation (MAC used with confidence since its introduction in 1967. It is found that (i the MCA-based 2nd-order HTSE unexpectedly and depressingly fails for most situations investigated, and the present simulation results can serve well as strict criteria for testing liquid state theories. (ii The CPSE perturbation scheme is shown to be capable of predicting very accurately most of the thermodynamic properties simulated, but the most appropriate level of truncating the CPSE differs and depends on the range of the potential to be calculated; in particular, the shorter the potential range is, the higher the most appropriate truncating level can be, and along with rising of the potential range the performance of the CPSE perturbation scheme will decrease at higher truncating level. (iii The CPSE perturbation scheme can calculate satisfactorily bulk fluid rdf, and such calculations can be done for all fluid states of the whole phase diagram. (iv The CPSE is a convergent series at higher temperatures, but show attribute of asymptotic series at lower temperatures, and as a result, the surest asymptotic value occurs at lower-order truncation.

  18. Potential of Sentinel-1 Radar Data for the Assessment of Soil and Cereal Cover Parameters.

    Science.gov (United States)

    Bousbih, Safa; Zribi, Mehrez; Lili-Chabaane, Zohra; Baghdadi, Nicolas; El Hajj, Mohammad; Gao, Qi; Mougenot, Bernard

    2017-11-14

    The main objective of this study is to analyze the potential use of Sentinel-1 (S1) radar data for the estimation of soil characteristics (roughness and water content) and cereal vegetation parameters (leaf area index (LAI), and vegetation height (H)) in agricultural areas. Simultaneously to several radar acquisitions made between 2015 and 2017, using S1 sensors over the Kairouan Plain (Tunisia, North Africa), ground measurements of soil roughness, soil water content, LAI and H were recorded. The NDVI (normalized difference vegetation index) index computed from Landsat optical images revealed a strong correlation with in situ measurements of LAI. The sensitivity of the S1 measurements to variations in soil moisture, which has been reported in several scientific publications, is confirmed in this study. This sensitivity decreases with increasing vegetation cover growth (NDVI), and is stronger in the VV (vertical) polarization than in the VH cross-polarization. The results also reveal a similar increase in the dynamic range of radar signals observed in the VV and VH polarizations as a function of soil roughness. The sensitivity of S1 measurements to vegetation parameters (LAI and H) in the VV polarization is also determined, showing that the radar signal strength decreases when the vegetation parameters increase. No vegetation parameter sensitivity is observed in the VH polarization, probably as a consequence of volume scattering effects.

  19. Potential of Sentinel-1 Radar Data for the Assessment of Soil and Cereal Cover Parameters

    Directory of Open Access Journals (Sweden)

    Safa Bousbih

    2017-11-01

    Full Text Available The main objective of this study is to analyze the potential use of Sentinel-1 (S1 radar data for the estimation of soil characteristics (roughness and water content and cereal vegetation parameters (leaf area index (LAI, and vegetation height (H in agricultural areas. Simultaneously to several radar acquisitions made between 2015 and 2017, using S1 sensors over the Kairouan Plain (Tunisia, North Africa, ground measurements of soil roughness, soil water content, LAI and H were recorded. The NDVI (normalized difference vegetation index index computed from Landsat optical images revealed a strong correlation with in situ measurements of LAI. The sensitivity of the S1 measurements to variations in soil moisture, which has been reported in several scientific publications, is confirmed in this study. This sensitivity decreases with increasing vegetation cover growth (NDVI, and is stronger in the VV (vertical polarization than in the VH cross-polarization. The results also reveal a similar increase in the dynamic range of radar signals observed in the VV and VH polarizations as a function of soil roughness. The sensitivity of S1 measurements to vegetation parameters (LAI and H in the VV polarization is also determined, showing that the radar signal strength decreases when the vegetation parameters increase. No vegetation parameter sensitivity is observed in the VH polarization, probably as a consequence of volume scattering effects.

  20. Urocortin2 prolongs action potential duration and modulates potassium currents in guinea pig myocytes and HEK293 cells.

    Science.gov (United States)

    Yang, Li-Zhen; Zhu, Yi-Chun

    2015-07-05

    We previously reported that activation of corticotropin releasing factor receptor type 2 by urocortin2 up-regulates both L-type Ca(2+) channels and intracellular Ca(2+) concentration in ventricular myocytes and plays an important role in cardiac contractility and arrhythmogenesis. This study goal was to further test the hypothesis that urocortin2 may modulate action potentials as well as rapidly and slowly activating delayed rectifier potassium currents. With whole cell patch-clamp techniques, action potentials and slowly activating delayed rectifier potassium currents were recorded in isolated guinea pig ventricular myocytes, respectively. And rapidly activating delayed rectifier potassium currents were tested in hERG-HEK293 cells. Urocortin2 produced a time- and concentration-dependent prolongation of action potential duration. The EC50 values of action potential duration and action potential duration at 90% of repolarization were 14.73 and 24.3nM respectively. The prolongation of action potential duration of urocortin2 was almost completely or partly abolished by H-89 (protein kinase A inhibitor) or KB-R7943 (Na(+)/Ca(2+) exchange inhibitor) pretreatment respectively. And urocortin2 caused reduction of rapidly activating delayed rectifier potassium currents in hERG-HEK293 cells. In addition, urocortin2 slowed the rate of slowly activating delayed rectifier potassium channel activation, and rightward shifted the threshold of slowly activating delayed rectifier potassium currents to more positive potentials. Urocortin2 prolonged action potential duration via activation of protein kinase A and Na(+)/ Ca(2+) exchange in isolated guinea pig ventricular myocytes in a time- and concentration- dependent manner. In hERG-HEK293 cells, urocortin2 reduced rapidly activating delayed rectifier potassium current density which may contribute to action potential duration prolongation. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Sensitivity analysis and parameter estimation for distributed hydrological modeling: potential of variational methods

    Science.gov (United States)

    Castaings, W.; Dartus, D.; Le Dimet, F.-X.; Saulnier, G.-M.

    2009-04-01

    Variational methods are widely used for the analysis and control of computationally intensive spatially distributed systems. In particular, the adjoint state method enables a very efficient calculation of the derivatives of an objective function (response function to be analysed or cost function to be optimised) with respect to model inputs. In this contribution, it is shown that the potential of variational methods for distributed catchment scale hydrology should be considered. A distributed flash flood model, coupling kinematic wave overland flow and Green Ampt infiltration, is applied to a small catchment of the Thoré basin and used as a relatively simple (synthetic observations) but didactic application case. It is shown that forward and adjoint sensitivity analysis provide a local but extensive insight on the relation between the assigned model parameters and the simulated hydrological response. Spatially distributed parameter sensitivities can be obtained for a very modest calculation effort (~6 times the computing time of a single model run) and the singular value decomposition (SVD) of the Jacobian matrix provides an interesting perspective for the analysis of the rainfall-runoff relation. For the estimation of model parameters, adjoint-based derivatives were found exceedingly efficient in driving a bound-constrained quasi-Newton algorithm. The reference parameter set is retrieved independently from the optimization initial condition when the very common dimension reduction strategy (i.e. scalar multipliers) is adopted. Furthermore, the sensitivity analysis results suggest that most of the variability in this high-dimensional parameter space can be captured with a few orthogonal directions. A parametrization based on the SVD leading singular vectors was found very promising but should be combined with another regularization strategy in order to prevent overfitting.

  2. Sensitivity analysis and parameter estimation for distributed hydrological modeling: potential of variational methods

    Directory of Open Access Journals (Sweden)

    W. Castaings

    2009-04-01

    Full Text Available Variational methods are widely used for the analysis and control of computationally intensive spatially distributed systems. In particular, the adjoint state method enables a very efficient calculation of the derivatives of an objective function (response function to be analysed or cost function to be optimised with respect to model inputs.

    In this contribution, it is shown that the potential of variational methods for distributed catchment scale hydrology should be considered. A distributed flash flood model, coupling kinematic wave overland flow and Green Ampt infiltration, is applied to a small catchment of the Thoré basin and used as a relatively simple (synthetic observations but didactic application case.

    It is shown that forward and adjoint sensitivity analysis provide a local but extensive insight on the relation between the assigned model parameters and the simulated hydrological response. Spatially distributed parameter sensitivities can be obtained for a very modest calculation effort (~6 times the computing time of a single model run and the singular value decomposition (SVD of the Jacobian matrix provides an interesting perspective for the analysis of the rainfall-runoff relation.

    For the estimation of model parameters, adjoint-based derivatives were found exceedingly efficient in driving a bound-constrained quasi-Newton algorithm. The reference parameter set is retrieved independently from the optimization initial condition when the very common dimension reduction strategy (i.e. scalar multipliers is adopted.

    Furthermore, the sensitivity analysis results suggest that most of the variability in this high-dimensional parameter space can be captured with a few orthogonal directions. A parametrization based on the SVD leading singular vectors was found very promising but should be combined with another regularization strategy in order to prevent overfitting.

  3. Regulation of action potential waveforms by axonal GABAA receptors in cortical pyramidal neurons.

    Directory of Open Access Journals (Sweden)

    Yang Xia

    Full Text Available GABAA receptors distributed in somatodendritic compartments play critical roles in regulating neuronal activities, including spike timing and firing pattern; however, the properties and functions of GABAA receptors at the axon are still poorly understood. By recording from the cut end (bleb of the main axon trunk of layer -5 pyramidal neurons in prefrontal cortical slices, we found that currents evoked by GABA iontophoresis could be blocked by picrotoxin, indicating the expression of GABAA receptors in axons. Stationary noise analysis revealed that single-channel properties of axonal GABAA receptors were similar to those of somatic receptors. Perforated patch recording with gramicidin revealed that the reversal potential of the GABA response was more negative than the resting membrane potential at the axon trunk, suggesting that GABA may hyperpolarize the axonal membrane potential. Further experiments demonstrated that the activation of axonal GABAA receptors regulated the amplitude and duration of action potentials (APs and decreased the AP-induced Ca2+ transients at the axon. Together, our results indicate that the waveform of axonal APs and the downstream Ca2+ signals are modulated by axonal GABAA receptors.

  4. Parameter estimation in neuronal stochastic differential equation models from intracellular recordings of membrane potentials in single neurons

    DEFF Research Database (Denmark)

    Ditlevsen, Susanne; Samson, Adeline

    2016-01-01

    Dynamics of the membrane potential in a single neuron can be studied by estimating biophysical parameters from intracellular recordings. Diffusion processes, given as continuous solutions to stochastic differential equations, are widely applied as models for the neuronal membrane potential evolut...

  5. Ventricular filling slows epicardial conduction and increases action potential duration in an optical mapping study of the isolated rabbit heart

    Science.gov (United States)

    Sung, Derrick; Mills, Robert W.; Schettler, Jan; Narayan, Sanjiv M.; Omens, Jeffrey H.; McCulloch, Andrew D.; McCullough, A. D. (Principal Investigator)

    2003-01-01

    INTRODUCTION: Mechanical stimulation can induce electrophysiologic changes in cardiac myocytes, but how mechanoelectric feedback in the intact heart affects action potential propagation remains unclear. METHODS AND RESULTS: Changes in action potential propagation and repolarization with increased left ventricular end-diastolic pressure from 0 to 30 mmHg were investigated using optical mapping in isolated perfused rabbit hearts. With respect to 0 mmHg, epicardial strain at 30 mmHg in the anterior left ventricle averaged 0.040 +/- 0.004 in the muscle fiber direction and 0.032 +/- 0.006 in the cross-fiber direction. An increase in ventricular loading increased average epicardial activation time by 25%+/- 3% (P action potential duration at 20% repolarization (APD20) but did at 80% repolarization (APD80), from 179 +/- 7 msec to 207 +/- 5 msec (P action potential duration by a load-dependent mechanism that may not involve stretch-activated channels.

  6. The Belem Framework for Action: Harnessing the Power and Potential of Adult Learning and Education for a Viable Future

    Science.gov (United States)

    Adult Learning, 2012

    2012-01-01

    This article presents the Belem Framework for Action. This framework focuses on harnessing the power and potential of adult learning and education for a viable future. This framework begins with a preamble on adult education and towards lifelong learning.

  7. Influence of kinetic effects on a sheath potential and divertor plasma parameters in ITER

    Energy Technology Data Exchange (ETDEWEB)

    Krasheninnikov, S.I.; Soboleva, T.K.; Igitkhanov, Yu.L.; Runov, A.M. (Kurchatov Institute, Moscow (Russian Federation))

    1991-01-01

    It was already noted that strong inhomogeneity of ITER divertor plasma parameters may be a reason of a pronounced deviation of a sheath potential U[sub d] at a plasma-divertor plate contact from the local value U[sub d][approx]3.5T[sub d] (T[sub d] is an electron temperature in a vicinity of the divertor plate). This effect may badly influence the divertor plates sputtering resulting in a plasma contamination. (author) 6 refs., 5 figs.

  8. Prediction of Thorough QT study results using action potential simulations based on ion channel screens.

    Science.gov (United States)

    Mirams, Gary R; Davies, Mark R; Brough, Stephen J; Bridgland-Taylor, Matthew H; Cui, Yi; Gavaghan, David J; Abi-Gerges, Najah

    2014-01-01

    Detection of drug-induced pro-arrhythmic risk is a primary concern for pharmaceutical companies and regulators. Increased risk is linked to prolongation of the QT interval on the body surface ECG. Recent studies have shown that multiple ion channel interactions can be required to predict changes in ventricular repolarisation and therefore QT intervals. In this study we attempt to predict the result of the human clinical Thorough QT (TQT) study, using multiple ion channel screening which is available early in drug development. Ion current reduction was measured, in the presence of marketed drugs which have had a TQT study, for channels encoded by hERG, CaV1.2, NaV1.5, KCNQ1/MinK, and Kv4.3/KChIP2.2. The screen was performed on two platforms - IonWorks Quattro (all 5 channels, 34 compounds), and IonWorks Barracuda (hERG & CaV1.2, 26 compounds). Concentration-effect curves were fitted to the resulting data, and used to calculate a percentage reduction in each current at a given concentration. Action potential simulations were then performed using the ten Tusscher and Panfilov (2006), Grandi et al. (2010) and O'Hara et al. (2011) human ventricular action potential models, pacing at 1Hz and running to steady state, for a range of concentrations. We compared simulated action potential duration predictions with the QT prolongation observed in the TQT studies. At the estimated concentrations, simulations tended to underestimate any observed QT prolongation. When considering a wider range of concentrations, and conventional patch clamp rather than screening data for hERG, prolongation of ≥5ms was predicted with up to 79% sensitivity and 100% specificity. This study provides a proof-of-principle for the prediction of human TQT study results using data available early in drug development. We highlight a number of areas that need refinement to improve the method's predictive power, but the results suggest that such approaches will provide a useful tool in cardiac safety

  9. Differential contribution of sodium channel subtypes to action potential generation in unmyelinated human C-type nerve fibers.

    Science.gov (United States)

    Lang, Philip M; Hilmer, Verena B; Grafe, Peter

    2007-09-01

    Multiple voltage-dependent sodium channels (Na(v)) contribute to action potentials and excitability of primary nociceptive neurons. The aim of the current study was to characterize subtypes of Na(v) that contribute to action potential generation in peripheral unmyelinated human C-type nerve fibers. Registration of C-fiber compound action potentials and determination of membrane threshold was performed by a computerized threshold tracking program. Nerve fibers were stimulated with a 1-ms current pulse either alone or after a small ramp current lasting 300 ms. Compound C-fiber action potentials elicited by supramaximal 1-ms current pulses were rather resistant to application of tetrodotoxin (30-90 nM). However, the same concentrations of tetrodotoxin strongly reduced the peak height and elevated membrane threshold of action potentials evoked at the end of a 300-ms current ramp. A similar effect was observed during application of lidocaine and mexiletine (50 microM each). These data indicate that more than one type of Na(v) contributes to the generation of action potentials in unmyelinated human C-type nerve fibers. The peak height of an action potential produced by a short electrical impulse is dependent on the activation of tetrodotoxin-resistant ion channels. In contrast, membrane threshold and action potential peak height at the end of a slow membrane depolarization are regulated by a subtype of Na(v) with high sensitivity to low concentrations of tetrodotoxin, lidocaine, and mexiletine. The electrophysiologic and pharmacologic characteristics may indicate the functional activity of the Na(v) 1.7 subtype of voltage-dependent sodium channels.

  10. Potential Mechanisms of Action in the Treatment of Social Impairment and Disorganization in Adolescents with ADHD.

    Science.gov (United States)

    Sadler, Joanna M; Evans, Steven W; Schultz, Brandon K; Zoromski, Allison K

    2011-09-01

    Two important domains that can be impaired in adolescents with ADHD are organization and social functioning; however, the development of interventions to target these areas in adolescents is in the early stages. Currently, small efficacy trials are beginning to be used to conduct preliminary tests on the proposed mechanisms of action for these interventions. These two studies examined the efficacy of organization and social functioning interventions for adolescents with ADHD, as well as the potential mechanisms of action for each intervention. Results from the organization intervention provide support for a significant relationship between performance on the organization checklist and overall GPA; however, there was no meaningful pattern of relationships between achieving mastery of the organization tasks and grades within quarter. Further, results from the social functioning intervention support a moderate relationship between performance on process measures of response to the intervention and outcome measures of social functioning. Results of this study provide implications for modifications to the measures and intervention procedures in future research.

  11. The VCS parameters: Potential hematological indicators for predicting antituberculosis drug-induced neutropenia.

    Science.gov (United States)

    Shen, Tian; Gu, Delin; Zhu, Yihua; Shi, Junwei; Xu, Dongsheng; Cao, Xingjian

    2016-08-01

    The morphological changes in activated neutrophils associated with antituberculosis drugs can be measured by volume, conductivity, and scatter (VCS) technology on the Coulter LH750 hematology analyzer. We conducted the current study to further validate the clinical usefulness of the neutrophil VCS parameters in predicting drug-induced neutropenia. Peripheral blood samples were collected from 52 patients with drug-induced neutropenia, 309 patients without any abnormal CBC, and 237 healthy controls. The mean neutrophil volume (MNV) with its distribution width (NDW) and the mean neutrophil scatter (MNS) were studied. We observed a significant increase in the MNV and NDW as well as a significant decrease in the MNS in neutropenia patients approximately one week prior to development of neutropenia compared to healthy controls as well as to case controls. In addition, the delta MNV and delta MNS were respectively correlated well with delta absolute neutrophil counts when neutropenia occurred. The ROC curve analyses showed that the MNV、NDW and MNS had larger areas under curves compared to conventional parameters. With a cutoff of 150.15 for the MNV, a sensitivity of 84.4% and specificity of 75.7% were achieved prior to neutropenia. The neutrophil VCS parameters may be clinically useful as potential hematological indicators for predicting antituberculosis drug-induced neutropenia. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Firm’s Innovation Expectation, Potential and Actions: Impressions on the Japanese Videogame Console Market

    Directory of Open Access Journals (Sweden)

    Paulo Antônio Zawislak

    2009-12-01

    Full Text Available Under the theoretical developments proposed by the Theory of the Firm, it is possible to understand the firm as the primary site for innovation. Innovation effort is justified by the need to generate solutions which should be validated in the market. This market validation process enables one to identify the life cycle of the solution, represented by the “S-curve”. Whether due to its sales volume, market share and even technological improvements, there is a sequence of events that are, invariably, repeated in all technologies: onset, growth, maturing and decay. This paper presents, based on a model for innovation expectation and potential, an analysis of the firms’ actions along different S-curves. To do this, sales volume historical data of videogame consoles in Japan were used. The most interesting finding is that the firms terminate the life cycle of each technology keeping, simultaneously, two or more different versions of the consoles.

  13. Action Potential Modulation of Neural Spin Networks Suggests Possible Role of Spin

    CERN Document Server

    Hu, H P

    2004-01-01

    In this paper we show that nuclear spin networks in neural membranes are modulated by action potentials through J-coupling, dipolar coupling and chemical shielding tensors and perturbed by microscopically strong and fluctuating internal magnetic fields produced largely by paramagnetic oxygen. We suggest that these spin networks could be involved in brain functions since said modulation inputs information carried by the neural spike trains into them, said perturbation activates various dynamics within them and the combination of the two likely produce stochastic resonance thus synchronizing said dynamics to the neural firings. Although quantum coherence is desirable and may indeed exist, it is not required for these spin networks to serve as the subatomic components for the conventional neural networks.

  14. Spatial heterogeneity of myocardial perfusion predicts local potassium channel expression and action potential duration.

    Science.gov (United States)

    Stoll, Marion; Quentin, Michael; Molojavyi, Andrej; Thämer, Volker; Decking, Ulrich K M

    2008-02-01

    In the heart, there is not only a transmural gradient of left ventricular perfusion and action potential duration (APD), but also spatial heterogeneity within each myocardial layer, where local blood flow and energy turnover vary more than three-fold between individual regions. We analysed at high spatial resolution whether a corresponding heterogeneity also extends to ion channel gene expression and APD. In the open-chest beagle dog, left ventricular 300 microL samples of very low or high flow were identified by radioactive microspheres and expression levels determined by quantitative PCR. The distribution of epicardial APD was assessed by mapping local activation repolarization intervals (ARIs) and QT interval (QT). ERG, the potassium channel mediating IKr, and KChIP2, the interacting protein modulating Ito, were increased in Low flow (3.3- and 2.5-fold, P channel expression and APD. Whenever this newly recognized intramural dispersion of APD increases, it may contribute to arrhythmogenesis.

  15. Mechanism of Action and Clinical Potential of Fingolimod for the Treatment of Stroke

    Directory of Open Access Journals (Sweden)

    Wentao Li

    2016-08-01

    Full Text Available Fingolimod (FTY720 is an orally bio-available immunomodulatory drug currently approved by the FDA for the treatment of multiple sclerosis. Currently, there is a significant interest in the potential benefits of FTY720 on stroke outcomes. FTY720 and the sphingolipid signaling pathway it modulates has a ubiquitous presence in the central nervous system and both rodent models and pilot clinical trials seem to indicate that the drug may improve overall functional recovery in different stroke subtypes. Although the precise mechanisms behind these beneficial effects are yet unclear, there is evidence that FTY720 has a role in regulating cerebrovascular responses, blood brain barrier permeability, and cell survival in the event of cerebrovascular insult. In this article, we critically review the data obtained from the latest laboratory findings and clinical trials involving both ischemic and hemorrhagic stroke, and attempt to form a cohesive picture of FTY720’s mechanisms of action in stroke

  16. Effect of sampling frequency on the measurement of phase-locked action potentials.

    Directory of Open Access Journals (Sweden)

    Go eAshida

    2010-09-01

    Full Text Available Phase-locked spikes in various types of neurons encode temporal information. To quantify the degree of phase-locking, the metric called vector strength (VS has been most widely used. Since VS is derived from spike timing information, error in measurement of spike occurrence should result in errors in VS calculation. In electrophysiological experiments, the timing of an action potential is detected with finite temporal precision, which is determined by the sampling frequency. In order to evaluate the effects of the sampling frequency on the measurement of VS, we derive theoretical upper and lower bounds of VS from spikes collected with finite sampling rates. We next estimate errors in VS assuming random sampling effects, and show that our theoretical calculation agrees with data from electrophysiological recordings in vivo. Our results provide a practical guide for choosing the appropriate sampling frequency in measuring VS.

  17. Iridium oxide nanotube electrodes for sensitive and prolonged intracellular measurement of action potentials

    Science.gov (United States)

    Lin, Ziliang Carter; Xie, Chong; Osakada, Yasuko; Cui, Yi; Cui, Bianxiao

    2014-02-01

    Intracellular recording of action potentials is important to understand electrically-excitable cells. Recently, vertical nanoelectrodes have been developed to achieve highly sensitive, minimally invasive and large-scale intracellular recording. It has been demonstrated that the vertical geometry is crucial for the enhanced signal detection. Here we develop nanoelectrodes of a new geometry, namely nanotubes of iridium oxide. When cardiomyocytes are cultured upon those nanotubes, the cell membrane not only wraps around the vertical tubes but also protrudes deep into the hollow centre. We show that this nanotube geometry enhances cell-electrode coupling and results in larger signals than solid nanoelectrodes. The nanotube electrodes also afford much longer intracellular access and are minimally invasive, making it possible to achieve stable recording up to an hour in a single session and more than 8 days of consecutive daily recording. This study suggests that the nanoelectrode performance can be significantly improved by optimizing the electrode geometry.

  18. Fast sodium channel gating supports localized and efficient axonal action potential initiation.

    Science.gov (United States)

    Schmidt-Hieber, Christoph; Bischofberger, Josef

    2010-07-28

    Action potentials (APs) are initiated in the proximal axon of most neurons. In myelinated axons, a 50-times higher sodium channel density in the initial segment compared to the soma may account for this phenomenon. However, little is known about sodium channel density and gating in proximal unmyelinated axons. To study the mechanisms underlying AP initiation in unmyelinated hippocampal mossy fibers of adult mice, we recorded sodium currents in axonal and somatic membrane patches. We demonstrate that sodium channel density in the proximal axon is approximately 5 times higher than in the soma. Furthermore, sodium channel activation and inactivation are approximately 2 times faster. Modeling revealed that the fast activation localized the initiation site to the proximal axon even upon strong synaptic stimulation, while fast inactivation contributed to energy-efficient membrane charging during APs. Thus, sodium channel gating and density in unmyelinated mossy fiber axons appear to be specialized for robust AP initiation and propagation with minimal current flow.

  19. Comparison of three spike detectors dedicated to single unit action potentials of the auditory nerve.

    Science.gov (United States)

    Bourien, J; Ruel, J; Senhadji, L; Puel, J L

    2007-01-01

    This paper compares three methods for the detection of single unit action potentials in auditory nerve. The detector structures are similar consisting of a filtering procedure in the first stage and a decision rule in the second stage. The detection accuracy of each detector is characterized by the couple probability of a true detection vs. rates of false detection with synthetic data. The performance comparison between detectors shows that the detector using a band-pass finite-impulse-response filter with complex coefficients offers the best performance. This observation was especially evident for low signal to noise ratios. This finding is confirmed with real data and leads us to revise the protocol of spike detection in auditory nerve.

  20. miR-19b Regulates Ventricular Action Potential Duration in Zebrafish

    Science.gov (United States)

    Benz, Alexander; Kossack, Mandy; Auth, Dominik; Seyler, Claudia; Zitron, Edgar; Juergensen, Lonny; Katus, Hugo A.; Hassel, David

    2016-01-01

    Sudden cardiac death due to ventricular arrhythmias often caused by action potential duration (APD) prolongation is a common mode of death in heart failure (HF). microRNAs, noncoding RNAs that fine tune gene expression, are frequently dysregulated during HF, suggesting a potential involvement in the electrical remodeling process accompanying HF progression. Here, we identified miR-19b as an important regulator of heart function. Zebrafish lacking miR-19b developed severe bradycardia and reduced cardiac contractility. miR-19b deficient fish displayed increased sensitivity to AV-block, a characteristic feature of long QT syndrome in zebrafish. Patch clamp experiments from whole hearts showed that miR-19b deficient zebrafish exhibit significantly prolonged ventricular APD caused by impaired repolarization. We found that miR-19b directly and indirectly regulates the expression of crucial modulatory subunits of cardiac ion channels, and thereby modulates AP duration and shape. Interestingly, miR-19b knockdown mediated APD prolongation can rescue a genetically induced short QT phenotype. Thus, miR-19b might represent a crucial modifier of the cardiac electrical activity, and our work establishes miR-19b as a potential candidate for human long QT syndrome. PMID:27805004

  1. Biochemical methane potential (BMP) tests: Reducing test time by early parameter estimation.

    Science.gov (United States)

    Da Silva, C; Astals, S; Peces, M; Campos, J L; Guerrero, L

    2018-01-01

    Biochemical methane potential (BMP) test is a key analytical technique to assess the implementation and optimisation of anaerobic biotechnologies. However, this technique is characterised by long testing times (from 20 to >100days), which is not suitable for waste utilities, consulting companies or plants operators whose decision-making processes cannot be held for such a long time. This study develops a statistically robust mathematical strategy using sensitivity functions for early prediction of BMP first-order model parameters, i.e. methane yield (B 0 ) and kinetic constant rate (k). The minimum testing time for early parameter estimation showed a potential correlation with the k value, where (i) slowly biodegradable substrates (k≤0.1d -1 ) have a minimum testing times of ≥15days, (ii) moderately biodegradable substrates (0.1

  2. The effects of passivation parameters on pitting potential of biomedical stainless steel

    Directory of Open Access Journals (Sweden)

    Petković Dušan Lj.

    2017-01-01

    Full Text Available Passivation is a chemical process in which the electrochemical condition of passivity is gained on the surface of metal alloys. Biomedical AISI 316LVM stainless steel (SS can be passivized by means of nitric acid immersion in order to improve a protective oxide layer on the surface and consequently increase corrosion resistance of the SS in the physiological solutions. In this study, multiple regression analysis and artificial neural network (ANN were employed for mathematical modeling of the AISI 316LVM SS passivation process after immersion in the nitric acid solution. The pitting potential, which represents the mea-sure of pitting corrosion resistance, was chosen as the response, while the passivation parameters were nitric acid concentration, temperature and passivation time. The comparison between experimental results and models predictions showed that only the ANN model provided statistically accurate predictions with a high coefficient of determination and a low mean relative error. Finally, based on the derived ANN equation, the effects of the passivation parameters on pitting potential were examined. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. ON174004 and Grant no. TR35034

  3. Potential Value of Coagulation Parameters for Suggesting Preeclampsia During the Third Trimester of Pregnancy.

    Science.gov (United States)

    Chen, Ying; Lin, Li

    2017-07-01

    Preeclampsia is a relatively common complication of pregnancy and considered to be associated with different degrees of coagulation dysfunction. This study was developed to evaluate the potential value of coagulation parameters for suggesting preeclampsia during the third trimester of pregnancy. Data from 188 healthy pregnant women, 125 patients with preeclampsia in the third trimester and 120 age-matched nonpregnant women were analyzed. Prothrombin time, prothrombin activity, activated partial thromboplastin time, fibrinogen (Fg), antithrombin, platelet count, mean platelet volume, platelet distribution width and plateletcrit were tested. All parameters, excluding prothrombin time, platelet distribution width and plateletcrit, differed significantly between healthy pregnant women and those with preeclampsia. Platelet count, antithrombin and Fg were significantly lower and mean platelet volume and prothrombin activity were significantly higher in patients with preeclampsia (P preeclampsia was 0.872 for Fg with an optimal cutoff value of ≤2.87g/L (sensitivity = 0.68 and specificity = 0.98). For severe preeclampsia, the area under the curve for Fg reached up to 0.922 with the same optimal cutoff value (sensitivity = 0.84, specificity = 0.98, positive predictive value = 0.96 and negative predictive value = 0.93). Fg is a biomarker suggestive of preeclampsia in the third trimester of pregnancy, and our data provide a potential cutoff value of Fg ≤ 2.87g/L for screening preeclampsia, especially severe preeclampsia. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  4. Glutamine and glutamate limit the shortening of action potential duration in anoxia-challenged rabbit hearts.

    Science.gov (United States)

    Drake, Kenneth J; Shotwell, Matthew S; Wikswo, John P; Sidorov, Veniamin Y

    2015-09-01

    In clinical conditions, amino acid supplementation is applied to improve contractile function, minimize ischemia/reperfusion injury, and facilitate postoperative recovery. It has been shown that glutamine enhances myocardial ATP/APD (action potential duration) and glutathione/oxidized glutathione ratios, and can increase hexosamine biosynthesis pathway flux, which is believed to play a role in cardioprotection. Here, we studied the effect of glutamine and glutamate on electrical activity in Langendorff-perfused rabbit hearts. The hearts were supplied by Tyrode's media with or without 2.5 mmol/L glutamine and 150 μmol/L glutamate, and exposed to two 6-min anoxias with 20-min recovery in between. Change in APD was detected using a monophasic action potential probe. A nonlinear mixed-effects regression technique was used to evaluate the effect of amino acids on APD over the experiment. Typically, the dynamic of APD change encompasses three phases: short transient increase (more prominent in the first episode), slow decrease, and fast increase (starting with the beginning of recovery). The effect of both anoxic challenge and glutamine/glutamate was cumulative, being more pronounced in the second anoxia. The amino acids' protective effect became largest by the end of anoxia - 20.0% (18.9, 95% CI: [2.6 ms, 35.1 ms]), during the first anoxia and 36.6% (27.1, 95% CI: [7.7 ms, 46.6 ms]), during the second. Following the second anoxia, APD difference between control and supplemented hearts progressively increased, attaining 10.8% (13.6, 95% CI: [4.1 ms, 23.1 ms]) at the experiments' end. Our data reveal APD stabilizing and suggest an antiarrhythmic capacity of amino acid supplementation in anoxic/ischemic conditions. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  5. Sodium Channel β2 Subunits Prevent Action Potential Propagation Failures at Axonal Branch Points.

    Science.gov (United States)

    Cho, In Ha; Panzera, Lauren C; Chin, Morven; Hoppa, Michael B

    2017-09-27

    Neurotransmitter release depends on voltage-gated Na + channels (Na v s) to propagate an action potential (AP) successfully from the axon hillock to a synaptic terminal. Unmyelinated sections of axon are very diverse structures encompassing branch points and numerous presynaptic terminals with undefined molecular partners of Na + channels. Using optical recordings of Ca 2+ and membrane voltage, we demonstrate here that Na + channel β2 subunits (Na v β2s) are required to prevent AP propagation failures across the axonal arborization of cultured rat hippocampal neurons (mixed male and female). When Na v β2 expression was reduced, we identified two specific phenotypes: (1) membrane excitability and AP-evoked Ca 2+ entry were impaired at synapses and (2) AP propagation was severely compromised with >40% of axonal branches no longer responding to AP-stimulation. We went on to show that a great deal of electrical signaling heterogeneity exists in AP waveforms across the axonal arborization independent of axon morphology. Therefore, Na v β2 is a critical regulator of axonal excitability and synaptic function in unmyelinated axons. SIGNIFICANCE STATEMENT Voltage-gated Ca 2+ channels are fulcrums of neurotransmission that convert electrical inputs into chemical outputs in the form of vesicle fusion at synaptic terminals. However, the role of the electrical signal, the presynaptic action potential (AP), in modulating synaptic transmission is less clear. What is the fidelity of a propagating AP waveform in the axon and what molecules shape it throughout the axonal arborization? Our work identifies several new features of AP propagation in unmyelinated axons: (1) branches of a single axonal arborization have variable AP waveforms independent of morphology, (2) Na + channel β2 subunits modulate AP-evoked Ca 2+ -influx, and (3) β2 subunits maintain successful AP propagation across the axonal arbor. These findings are relevant to understanding the flow of excitation in the

  6. BK channels regulate spontaneous action potential rhythmicity in the suprachiasmatic nucleus.

    Directory of Open Access Journals (Sweden)

    Jack Kent

    Full Text Available BACKGROUND: Circadian ( approximately 24 hr rhythms are generated by the central pacemaker localized to the suprachiasmatic nucleus (SCN of the hypothalamus. Although the basis for intrinsic rhythmicity is generally understood to rely on transcription factors encoded by "clock genes", less is known about the daily regulation of SCN neuronal activity patterns that communicate a circadian time signal to downstream behaviors and physiological systems. Action potentials in the SCN are necessary for the circadian timing of behavior, and individual SCN neurons modulate their spontaneous firing rate (SFR over the daily cycle, suggesting that the circadian patterning of neuronal activity is necessary for normal behavioral rhythm expression. The BK K(+ channel plays an important role in suppressing spontaneous firing at night in SCN neurons. Deletion of the Kcnma1 gene, encoding the BK channel, causes degradation of circadian behavioral and physiological rhythms. METHODOLOGY/PRINCIPAL FINDINGS: To test the hypothesis that loss of robust behavioral rhythmicity in Kcnma1(-/- mice is due to the disruption of SFR rhythms in the SCN, we used multi-electrode arrays to record extracellular action potentials from acute wild-type (WT and Kcnma1(-/- slices. Patterns of activity in the SCN were tracked simultaneously for up to 3 days, and the phase, period, and synchronization of SFR rhythms were examined. Loss of BK channels increased arrhythmicity but also altered the amplitude and period of rhythmic activity. Unexpectedly, Kcnma1(-/- SCNs showed increased variability in the timing of the daily SFR peak. CONCLUSIONS/SIGNIFICANCE: These results suggest that BK channels regulate multiple aspects of the circadian patterning of neuronal activity in the SCN. In addition, these data illustrate the characteristics of a disrupted SCN rhythm downstream of clock gene-mediated timekeeping and its relationship to behavioral rhythms.

  7. Modulation of KCNQ1 alternative splicing regulates cardiac IKs and action potential repolarization.

    Science.gov (United States)

    Lee, Hsiang-Chun; Rudy, Yoram; Po-Yuan, Phd; Sheu, Sheng-Hsiung; Chang, Jan-Gowth; Cui, Jianmin

    2013-08-01

    Slow delayed-rectifier potassium current (IKs) channels, made of the pore-forming KCNQ1 and auxiliary KCNE1 subunits, play a key role in determining action potential duration (APD) in cardiac myocytes. The consequences of drug-induced KCNQ1 splice alteration remain unknown. To study the modulation of KCNQ1 alternative splicing by amiloride and the consequent changes in IKs and action potentials (APs) in ventricular myocytes. Canine endocardial, midmyocardial, and epicardial ventricular myocytes were isolated. Levels of KCNQ1a and KCNQ1b as well as a series of splicing factors were quantified by using the reverse transcriptase-polymerase chain reaction and Western blot. The effect of amiloride-induced changes in the KCNQ1b/total KCNQ1 ratio on AP was measured by using whole-cell patch clamp with and without isoproterenol. With 50 μmol/L of amiloride for 6 hours, KCNQ1a at transcriptional and translational levels increased in midmyocardial myocytes but decreased in endo- and epicardial myocytes. Likewise, changes in splicing factors in midmyocardial were opposite to that in endo- and epicardial myocytes. In midmyocardial myocytes amiloride shortened APD and decreased isoproterenol-induced early afterdepolarizations significantly. The same amiloride-induced effects were demonstrated by using human ventricular myocyte model for AP simulations under beta-adrenergic stimulation. Moreover, amiloride reduced the transmural dispersion of repolarization in pseudo-electrocardiogram. Amiloride regulates IKs and APs with transmural differences and reduces arrhythmogenicity through the modulation of KCNQ1 splicing. We suggested that the modulation of KCNQ1 splicing may help prevent arrhythmia. Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  8. Sympathetic Nervous Regulation of Calcium and Action Potential Alternans in the Intact Heart.

    Science.gov (United States)

    Winter, James; Bishop, Martin J; Wilder, Catherine D E; O'Shea, Christopher; Pavlovic, Davor; Shattock, Michael J

    2018-01-01

    Rationale: Arrhythmogenic cardiac alternans are thought to be an important determinant for the initiation of ventricular fibrillation. There is limited information on the effects of sympathetic nerve stimulation (SNS) on alternans in the intact heart and the conclusions of existing studies, focused on investigating electrical alternans, are conflicted. Meanwhile, several lines of evidence implicate instabilities in Ca handling, not electrical restitution, as the primary mechanism underpinning alternans. Despite this, there have been no studies on Ca alternans and SNS in the intact heart. The present study sought to address this, by application of voltage and Ca optical mapping for the simultaneous study of APD and Ca alternans in the intact guinea pig heart during direct SNS. Objective : To determine the effects of SNS on APD and Ca alternans in the intact guinea pig heart and to examine the mechanism(s) by which the effects of SNS are mediated. Methods and Results : Studies utilized simultaneous voltage and Ca optical mapping in isolated guinea pig hearts with intact innervation. Alternans were induced using a rapid dynamic pacing protocol. SNS was associated with rate-independent shortening of action potential duration (APD) and the suppression of APD and Ca alternans, as indicated by a shift in the alternans threshold to faster pacing rates. Qualitatively similar results were observed with exogenous noradrenaline perfusion. In contrast with previous reports, both SNS and noradrenaline acted to flatten the slope of the electrical restitution curve. Pharmacological block of the slow delayed rectifying potassium current (I Ks ), sufficient to abolish I Ks -mediated APD-adaptation, partially reversed the effects of SNS on pacing-induced alternans. Treatment with cyclopiazonic acid, an inhibitor of the sarco(endo)plasmic reticulum ATPase, had opposite effects to that of SNS, acting to increase susceptibility to alternans, and suggesting that accelerated Ca reuptake

  9. The Potential Therapeutic Agent Mepacrine Protects Caco-2 Cells against Clostridium perfringens Enterotoxin Action.

    Science.gov (United States)

    Freedman, John C; Hendricks, Matthew R; McClane, Bruce A

    2017-01-01

    Clostridium perfringens enterotoxin (CPE) causes the diarrhea associated with a common bacterial food poisoning and many antibiotic-associated diarrhea cases. The severity of some CPE-mediated disease cases warrants the development of potential therapeutics. A previous study showed that the presence of mepacrine inhibited CPE-induced electrophysiology effects in artificial lipid bilayers lacking CPE receptors. However, that study did not assess whether mepacrine inactivates CPE or, instead, inhibits a step in CPE action. Furthermore, CPE action in host cells is complex, involving the toxin binding to receptors, receptor-bound CPE oligomerizing into a prepore on the membrane surface, and β-hairpins in the CPE prepore inserting into the membrane to form a pore that induces cell death. Therefore, the current study evaluated the ability of mepacrine to protect cells from CPE. This drug was found to reduce CPE-induced cytotoxicity in Caco-2 cells. This protection did not involve mepacrine inactivation of CPE, indicating that mepacrine affects one or more steps in CPE action. Western blotting then demonstrated that mepacrine decreases CPE pore levels in Caco-2 cells. This mepacrine-induced reduction in CPE pore levels did not involve CPE binding inhibition but rather an increase in CPE monomer dissociation due to mepacrine interactions with Caco-2 membranes. In addition, mepacrine was also shown to inhibit CPE pores when already present in Caco-2 cells. These in vitro studies, which identified two mepacrine-sensitive steps in CPE-induced cytotoxicity, add support to further testing of the therapeutic potential of mepacrine against CPE-mediated disease. IMPORTANCEClostridium perfringens enterotoxin (CPE) causes the gastrointestinal (GI) symptoms of a common bacterial food poisoning and several nonfoodborne human GI diseases. A previous study showed that, via an undetermined mechanism, the presence of mepacrine blocks CPE-induced electrophysiologic activity in artificial

  10. Sympathetic Nervous Regulation of Calcium and Action Potential Alternans in the Intact Heart

    Directory of Open Access Journals (Sweden)

    James Winter

    2018-01-01

    Full Text Available Rationale: Arrhythmogenic cardiac alternans are thought to be an important determinant for the initiation of ventricular fibrillation. There is limited information on the effects of sympathetic nerve stimulation (SNS on alternans in the intact heart and the conclusions of existing studies, focused on investigating electrical alternans, are conflicted. Meanwhile, several lines of evidence implicate instabilities in Ca handling, not electrical restitution, as the primary mechanism underpinning alternans. Despite this, there have been no studies on Ca alternans and SNS in the intact heart. The present study sought to address this, by application of voltage and Ca optical mapping for the simultaneous study of APD and Ca alternans in the intact guinea pig heart during direct SNS.Objective: To determine the effects of SNS on APD and Ca alternans in the intact guinea pig heart and to examine the mechanism(s by which the effects of SNS are mediated.Methods and Results: Studies utilized simultaneous voltage and Ca optical mapping in isolated guinea pig hearts with intact innervation. Alternans were induced using a rapid dynamic pacing protocol. SNS was associated with rate-independent shortening of action potential duration (APD and the suppression of APD and Ca alternans, as indicated by a shift in the alternans threshold to faster pacing rates. Qualitatively similar results were observed with exogenous noradrenaline perfusion. In contrast with previous reports, both SNS and noradrenaline acted to flatten the slope of the electrical restitution curve. Pharmacological block of the slow delayed rectifying potassium current (IKs, sufficient to abolish IKs-mediated APD-adaptation, partially reversed the effects of SNS on pacing-induced alternans. Treatment with cyclopiazonic acid, an inhibitor of the sarco(endoplasmic reticulum ATPase, had opposite effects to that of SNS, acting to increase susceptibility to alternans, and suggesting that accelerated Ca

  11. Potential Beneficiaries of the Obama Administration’s Executive Action Programs Deeply Embedded in US Society

    Directory of Open Access Journals (Sweden)

    Donald Kerwin

    2016-03-01

    Full Text Available The Obama administration has developed two broad programs to defer immigration enforcement actions against undocumented persons living in the United States: (1 Deferred Action for Parents of Americans and Lawful Permanent Residents (DAPA; and (2 Deferred Action for Childhood Arrivals (DACA. The DACA program, which began in August 2012, was expanded on November 20, 2014. DAPA and the DACA expansion (hereinafter referred to as “DACA-plus” are currently under review by the US Supreme Court and subject to an active injunction.This paper offers a statistical portrait of the intended direct beneficiaries of DAPA, DACA, and DACA-plus. It finds that potential DAPA, DACA, and DACA-plus recipients are deeply embedded in US society, with high employment rates, extensive US family ties, long tenure, and substantial rates of English-language proficiency. The paper also notes various groups that would benefit indirectly from the full implementation of DAPA and DACA or, conversely, would suffer from the removal of potential beneficiaries of these programs. For example, all those who would rely on the retirement programs of the US government will benefit from the high employment rates and relative youth of the DACA population, while many US citizens who rely on the income of a DAPA-eligible parent would fall into poverty or extreme poverty should that parent be removed from the United States.This paper offers an analysis of potential DAPA and DACA beneficiaries. In an earlier study, the authors made the case for immigration reform based on long-term trends related to the US undocumented population, including potential DAPA and DACA beneficiaries (Warren and Kerwin 2015. By contrast, this paper details the degree to which these populations have become embedded in US society. It also compares persons eligible for the original DACA program with those eligible for DACA-plus.As stated, the great majority of potential DAPA and DACA recipients enjoy strong family

  12. Nocturnal heart rate variability parameters as potential fibromyalgia biomarker: correlation with symptoms severity.

    Science.gov (United States)

    Lerma, Claudia; Martinez, Aline; Ruiz, Natllely; Vargas, Angelica; Infante, Oscar; Martinez-Lavin, Manuel

    2011-01-01

    At present, there is neither a laboratory test nor an imaging technique able to differentiate people with fibromyalgia (FM) from healthy controls. This lack of an objective biomarker has hampered FM recognition and research. Heart rate variability (HRV) analyses provide a quantitative marker of autonomic nervous system activity. Nighttime is a stable period in which most people are resting. Sleep is modulated by autonomic activity. Sleeping problems are prominent in FM. The objectives of this study are: 1) to explore different nocturnal HRV parameters as potential FM biomarkers and 2) to seek correlation between such HRV parameters and diverse FM symptoms. We studied 22 women suffering from FM and 22 age-matched controls. All participants filled out several questionnaires related to FM symptoms. All participants used a Holter monitor over 24 hours while undertaking their routine activities during the day and while sleeping at their homes at night. Time-domain HRV parameters analyzed from 0000 to 0600 hours included, among others: mean normal-normal interbeat intervals (mean NN), standard deviation of the NN intervals (SDNN), and standard deviation of the successive NN differences (SDSD). Nocturnal SDNN of less than 114 ms had the greatest predictive value to set apart patients from controls with an odds ratio of 13.6 (95% confidence interval: 3.9 to 47.8). In patients, decreased nighttime HRV markers indicative of sympathetic predominance had significant correlations with several FM symptoms: SDSD was associated with pain intensity (r = -0.65, P = 0.001). SDNN correlated with constipation (r = -0.53, P = 0.001), and mean NN with depression (r = -0.53, P = 0.001). Controls displayed an opposite behavior. For them, increased nighttime SDNN correlated with Fibromyalgia Impact Questionnaire scores (r = 0.69, P = 0.001) and with other FM symptoms. Nocturnal HRV indices indicative of sympathetic predominance are significantly different in FM women when compared to

  13. A fluorescent, genetically-encoded voltage probe capable of resolving action potentials.

    Science.gov (United States)

    Barnett, Lauren; Platisa, Jelena; Popovic, Marko; Pieribone, Vincent A; Hughes, Thomas

    2012-01-01

    There is a pressing need in neuroscience for genetically-encoded, fluorescent voltage probes that can be targeted to specific neurons and circuits to allow study of neural activity using fluorescent imaging. We created 90 constructs in which the voltage sensing portion (S1-S4) of Ciona intestinalis voltage sensitive phosphatase (CiVSP) was fused to circularly permuted eGFP. This led to ElectricPk, a probe that is an order of magnitude faster (taus ~1-2 ms) than any currently published fluorescent protein-based voltage probe. ElectricPk can follow the rise and fall of neuronal action potentials with a modest decrease in fluorescence intensity (~0.7% ΔF/F). The probe has a nearly linear fluorescence/membrane potential response to both hyperpolarizing and depolarizing steps. This is the first probe based on CiVSP that captures the rapid movements of the voltage sensor, suggesting that voltage probes designed with circularly permuted fluorescent proteins may have some advantages.

  14. A fluorescent, genetically-encoded voltage probe capable of resolving action potentials.

    Directory of Open Access Journals (Sweden)

    Lauren Barnett

    Full Text Available There is a pressing need in neuroscience for genetically-encoded, fluorescent voltage probes that can be targeted to specific neurons and circuits to allow study of neural activity using fluorescent imaging. We created 90 constructs in which the voltage sensing portion (S1-S4 of Ciona intestinalis voltage sensitive phosphatase (CiVSP was fused to circularly permuted eGFP. This led to ElectricPk, a probe that is an order of magnitude faster (taus ~1-2 ms than any currently published fluorescent protein-based voltage probe. ElectricPk can follow the rise and fall of neuronal action potentials with a modest decrease in fluorescence intensity (~0.7% ΔF/F. The probe has a nearly linear fluorescence/membrane potential response to both hyperpolarizing and depolarizing steps. This is the first probe based on CiVSP that captures the rapid movements of the voltage sensor, suggesting that voltage probes designed with circularly permuted fluorescent proteins may have some advantages.

  15. Optophysiological approach to resolve neuronal action potentials with high spatial and temporal resolution in cultured neurons

    Directory of Open Access Journals (Sweden)

    Stephane ePages

    2011-10-01

    Full Text Available Cell to cell communication in the central nervous system is encoded into transient and local membrane potential changes (ΔVm. Deciphering the rules that govern synaptic transmission and plasticity entails to be able to perform Vm recordings throughout the entire neuronal arborization. Classical electrophysiology is, in most cases, not able to do so within small and fragile neuronal subcompartments. Thus, optical techniques based on the use of fluorescent voltage-sensitive dyes (VSDs have been developed. However, reporting spontaneous or small ΔVm from neuronal ramifications has been challenging, in part due to the limited sensitivity and phototoxicity of VSD-based optical measurements. Here we demonstrate the use of water soluble VSD, ANNINE-6plus, with laser scanning microscopy to optically record ΔVm in cultured neurons. We show that the sensitivity (> 10 % of fluorescence change for 100 mV depolarization and time response (submillisecond of the dye allows the robust detection of action potentials (APs even without averaging, allowing the measurement of spontaneous neuronal firing patterns. In addition, we show that back-propagating APs can be recorded, along distinct dendritic sites and within dendritic spines. Importantly, our approach does not induce any detectable phototoxic effect on cultured neurons. This optophysiological approach provides a simple, minimally invasive and versatile optical method to measure electrical activity in cultured neurons with high temporal (ms resolution and high spatial (µm resolution.

  16. Human neural tuning estimated from compound action potentials in normal hearing human volunteers

    Science.gov (United States)

    Verschooten, Eric; Desloovere, Christian; Joris, Philip X.

    2015-12-01

    The sharpness of cochlear frequency tuning in humans is debated. Evoked otoacoustic emissions and psychophysical measurements suggest sharper tuning in humans than in laboratory animals [15], but this is disputed based on comparisons of behavioral and electrophysiological measurements across species [14]. Here we used evoked mass potentials to electrophysiologically quantify tuning (Q10) in humans. We combined a notched noise forward masking paradigm [9] with the recording of trans tympanic compound action potentials (CAP) from masked probe tones in awake human and anesthetized monkey (Macaca mulatta). We compare our results to data obtained with the same paradigm in cat and chinchilla [16], and find that CAP-Q10values in human are ˜1.6x higher than in cat and chinchilla and ˜1.3x higher than in monkey. To estimate frequency tuning of single auditory nerve fibers (ANFs) in humans, we derive conversion functions from ANFs in cat, chinchilla, and monkey and apply these to the human CAP measurements. The data suggest that sharp cochlear tuning is a feature of old-world primates.

  17. Compound muscle action potential and motor function in children with spinal muscular atrophy.

    Science.gov (United States)

    Lewelt, Aga; Krosschell, Kristin J; Scott, Charles; Sakonju, Ai; Kissel, John T; Crawford, Thomas O; Acsadi, Gyula; D'anjou, Guy; Elsheikh, Bakri; Reyna, Sandra P; Schroth, Mary K; Maczulski, Jo Anne; Stoddard, Gregory J; Elovic, Elie; Swoboda, Kathryn J

    2010-11-01

    Reliable outcome measures that reflect the underlying disease process and correlate with motor function in children with SMA are needed for clinical trials. Maximum ulnar compound muscle action potential (CMAP) data were collected at two visits over a 4-6-week period in children with SMA types II and III, 2-17 years of age, at four academic centers. Primary functional outcome measures included the Modified Hammersmith Functional Motor Scale (MHFMS) and MHFMS-Extend. CMAP negative peak amplitude and area showed excellent discrimination between the ambulatory and non-ambulatory SMA cohorts (ROC = 0.88). CMAP had excellent test-retest reliability (ICC = 0.96-0.97, n = 64) and moderate to strong correlation with the MHFMS and MHFMS-Extend (r = 0.61-0.73, n = 68, P < 0.001). Maximum ulnar CMAP amplitude and area is a feasible, valid, and reliable outcome measure for use in pediatric multicenter clinical trials in SMA. CMAP correlates well with motor function and has potential value as a relevant surrogate for disease status.

  18. Honey as a Potential Natural Antioxidant Medicine: An Insight into Its Molecular Mechanisms of Action

    Science.gov (United States)

    Ahmed, Sarfraz; Sulaiman, Siti Amrah; Baig, Atif Amin; Ibrahim, Muhammad; Liaqat, Sana; Fatima, Saira; Jabeen, Sadia; Shamim, Nighat

    2018-01-01

    Honey clasps several medicinal and health effects as a natural food supplement. It has been established as a potential therapeutic antioxidant agent for various biodiverse ailments. Data report that it exhibits strong wound healing, antibacterial, anti-inflammatory, antifungal, antiviral, and antidiabetic effects. It also retains immunomodulatory, estrogenic regulatory, antimutagenic, anticancer, and numerous other vigor effects. Data also show that honey, as a conventional therapy, might be a novel antioxidant to abate many of the diseases directly or indirectly associated with oxidative stress. In this review, these wholesome effects have been thoroughly reviewed to underscore the mode of action of honey exploring various possible mechanisms. Evidence-based research intends that honey acts through a modulatory road of multiple signaling pathways and molecular targets. This road contemplates through various pathways such as induction of caspases in apoptosis; stimulation of TNF-α, IL-1β, IFN-γ, IFNGR1, and p53; inhibition of cell proliferation and cell cycle arrest; inhibition of lipoprotein oxidation, IL-1, IL-10, COX-2, and LOXs; and modulation of other diverse targets. The review highlights the research done as well as the apertures to be investigated. The literature suggests that honey administered alone or as adjuvant therapy might be a potential natural antioxidant medicinal agent warranting further experimental and clinical research. PMID:29492183

  19. Phase relationship between alternans of early and late phases of ventricular action potentials.

    Directory of Open Access Journals (Sweden)

    Linyuan eJing

    2012-06-01

    Full Text Available Background: Alternans of early phase and of duration of action potential (AP critically affect dispersion of refractoriness through their influence on conduction and repolarization. We investigated the phase relationship between the two alternans and its effect on conduction. Methods and Results: Transmembrane potentials recorded from ventricles of 8 swine and 3 canines during paced activation intervals of ≤ 300 ms were used to quantify alternans of maximum rate of depolarization (|dv/dt|max and of APD. Incidence of APD alternans was 62% and 76% in swine and canines. Alternans of APD was frequently accompanied with alternans of |dv/dt|max. Of these, 4 and 26 % were out of phase in swine and canines, i.e. low |dv/dt|max preceded long APD. Computer simulations show that out of phase alternans attenuate variation of wavelength and thus minimize formation of spatially discordant alternans. Conclusions: The spontaneous switching of phase relationship between alternans of depolarization and repolarization suggests that mechanisms underlying these alternans may operate independent of each other. The phase between these alternans can critically impact spatial dispersion of refractoriness and thus stability of conduction, with the in phase relation promoting transition from concord to discord while out of phase preventing formation of discord.

  20. Effect of phentolamine, alprenolol and prenylamine on maximum rate of rise of action potential in guinea-pig papillary muscles.

    Science.gov (United States)

    Sada, H

    1978-10-01

    Effects of phentolamine (13.3, 26.5 and 53.0 micron), alprenolol (3.5, 7.0 and 17.5 micron) and prenylamine (2.4, 4.8 and 11.9 micron) on the transmembrane potential were studied in isolated guinea-pig papillary muscles, superfused with Tyrode's solution. 1. Phentolamine, alprenolol and prenylamine reduced the maximum rate of rise of action potential (.Vmax) dose-dependently. Higher concentrations of phentolamine and prenylamine caused a loss of plateau in a majority of the preparations. Resting potential was not altered by any of the drugs. Readmittance of drug-free Tyrode's solution reversed these changes induced by 13.3 micron of phentolamine and all conconcentrations of alprenolol almost completely but those induced by higher concentrations of phentolamine and all concentrations of prenylamine only slightly. 2. .Vmax at steady state was increased with decreasing driving frequencies (0.5 and 0.25 Hz) and was decreased with increasing ones (2--5 Hz) in comparison with that at 1 Hz. Such changes were all exaggerated by the above drugs, particularly by prenylamine. 3. Prenylamine and, to a lesser degree, phentolamine and alprenolol delayed dose-dependently the recovery process of .Vmax in premature responses. 4. .Vmax in the first response after interruption of stimulation recovered toward the predrug value in the presence of the above three drugs. The time constants of recovery process ranged between 10.5 and 15.0s for phentolamine, between 4.5 and 15.5s for alprenolol. The time constant of the main component was estimated to be approximately 2s for the recovery process with prenylamine. 5. On the basis of the model recently proposed by Hondeghem and Katzung (1977), it is suggested that the drug molecules associate with the open sodium channels and dissociated slowly from the closed channels and that the inactivation parameter in the drug-associated channels is shifted in the hyperpolarizing direction.

  1. The effects of stimulus parameters on auditory evoked potentials of Carassius auratus.

    Science.gov (United States)

    Garabon, Jessica R; Higgs, Dennis M

    2017-11-01

    Whole-brain responses to sound are easily measured through auditory evoked potentials (AEP), but it is unclear how differences in experimental parameters affect these responses. The effect of varying parameters is especially unclear in fish studies, the majority of which use simple sound types and then extrapolate to natural conditions. The current study investigated AEPs in goldfish (Carassius auratus) using sounds of different durations (5, 10, and 20 ms) and frequencies (200, 500, 600 and 700 Hz) to test stimulus effects on latency and thresholds. We quantified differences in latency and threshold in comparison to a 10-ms test tone, a duration often used in AEP fish studies. Both response latency and threshold were significantly affected by stimulus duration, with latency patterning suggesting that AEP fires coincident with a decrease in stimulus strength. Response latency was also significantly affected by presentation frequency. These results show that stimulus type has important effects on AEP measures of hearing and call for clearer standards across different measures of AEP. Duration effects also suggest that AEP measures represent summed responses of duration-detecting neural circuit, but more effort is needed to understand the neural drivers of this commonly used technique.

  2. Comment on "Penetration of Action Potentials During Collision in the Median and Lateral Giant Axons of Invertebrates"

    DEFF Research Database (Denmark)

    Berg, Rune W.; Stauning, Marius Tving; Sorensen, Jakob Balslev

    2017-01-01

    The action potential (AP) is an electrical impulse elicited by depolarization of the neuronal membrane from the resting membrane potential (around − 70 mV). It propagates along the axon, allowing for rapid and distant communication. Recently, it was claimed that two APs traveling in opposite...

  3. Modifying welding process parameters can reduce the neurotoxic potential of manganese-containing welding fumes.

    Science.gov (United States)

    Sriram, Krishnan; Lin, Gary X; Jefferson, Amy M; Stone, Samuel; Afshari, Aliakbar; Keane, Michael J; McKinney, Walter; Jackson, Mark; Chen, Bean T; Schwegler-Berry, Diane; Cumpston, Amy; Cumpston, Jared L; Roberts, Jenny R; Frazer, David G; Antonini, James M

    2015-02-03

    Welding fumes (WF) are a complex mixture of toxic metals and gases, inhalation of which can lead to adverse health effects among welders. The presence of manganese (Mn) in welding electrodes is cause for concern about the potential development of Parkinson's disease (PD)-like neurological disorder. Consequently, from an occupational safety perspective, there is a critical need to prevent adverse exposures to WF. As the fume generation rate and physicochemical characteristics of welding aerosols are influenced by welding process parameters like voltage, current or shielding gas, we sought to determine if changing such parameters can alter the fume profile and consequently its neurotoxic potential. Specifically, we evaluated the influence of voltage on fume composition and neurotoxic outcome. Rats were exposed by whole-body inhalation (40 mg/m(3); 3h/day × 5 d/week × 2 weeks) to fumes generated by gas-metal arc welding using stainless steel electrodes (GMA-SS) at standard/regular voltage (25 V; RVSS) or high voltage (30 V; HVSS). Fumes generated under these conditions exhibited similar particulate morphology, appearing as chain-like aggregates; however, HVSS fumes comprised of a larger fraction of ultrafine particulates that are generally considered to be more toxic than their fine counterparts. Paradoxically, exposure to HVSS fumes did not elicit dopaminergic neurotoxicity, as monitored by the expression of dopaminergic and PD-related markers. We show that the lack of neurotoxicity is due to reduced solubility of Mn in HVSS fumes. Our findings show promise for process control procedures in developing prevention strategies for Mn-related neurotoxicity during welding; however, it warrants additional investigations to determine if such modifications can be suitably adapted at the workplace to avert or reduce adverse neurological risks. Published by Elsevier Ireland Ltd.

  4. Potentiating Action of Propofol at GABAA Receptors of Retinal Bipolar Cells

    Science.gov (United States)

    Yue, Lan; Xie, An; Bruzik, Karol S.; Frølund, Bente; Qian, Haohua

    2011-01-01

    Purpose. Propofol (2,6-diisopropyl phenol), a widely used systemic anesthetic, is known to potentiate GABAA receptor activity in a number of CNS neurons and to produce changes in electroretinographically recorded responses of the retina. However, little is known about propofol's effects on specific retinal neurons. The authors investigated the action of propofol on GABA-elicited membrane current responses of retinal bipolar cells, which have both GABAA and GABAC receptors. Methods. Single, enzymatically dissociated bipolar cells obtained from rat retina were treated with propofol delivered by brief application in combination with GABA or other pharmacologic agents or as a component of the superfusing medium. Results. When applied with GABA at subsaturating concentrations and with TPMPA (a known GABAC antagonist), propofol markedly increased the peak amplitude and altered the kinetics of the response. Propofol increased the response elicited by THIP (a GABAA-selective agonist), and the response was reduced by bicuculline (a GABAA antagonist). The response to 5-methyl I4AA, a GABAC-selective agonist, was not enhanced by propofol. Serial brief applications of (GABA + TPMPA + propofol) led to a progressive increase in peak response amplitude and, at higher propofol concentrations, additional changes that included a prolonged time course of response recovery. Pre-exposure of the cell to perfusing propofol typically enhanced the rate of development of potentiation produced by (GABA + TPMPA + propofol) applications. Conclusions. Propofol exerts a marked and selective potentiation on GABAA receptors of retinal bipolar cells. The data encourage the use of propofol in future studies of bipolar cell function. PMID:21071744

  5. Research on the changes of some physiological parameters in several fish species under the action of the talstar insecticide

    Directory of Open Access Journals (Sweden)

    Maria Cristina PONEPAL

    2010-05-01

    Full Text Available Talstar insecticide is labeled for numerous bugs and many other household pests and lawn pests. Bifenthrin is highly toxic to fish and aquatic arthropods. Bifenhrin LC50 values range from 0.0038 to17.8 μg/L and is only slightly toxic to both waterfowl and upland game birds (LD50 values range from 1.800 mg/kg to > 2.150 mg/kg. Bifenthrin had no effect on mollusks at its limit of water solubility. This study was carried out to analyze the effects of sublethal and lethal concentrations – from 0.000625 to 0.005 ml Talstar/l water on some physiological parameters (oxygen consumption, breathing frequency, number of erythrocytes on fish belonging to three species: prussian carp (Carassius auratus gibelio Bloch, bleak (Alburnus alburnus L. and perch (Perca fluviatilis L.. The acute and subacute toxicity of Talstar insecticide was evaluated in glass aquaria under semystatic conditions. The Tlastar product, under the concentrations from 0.000625 to 0.005 ml/l water, produces, after one week of immersion, a significant decrease of the fish oxygen consumption. The insecticide has changed the fish respiratory rhythm in all investigated concentrations after seven days of exposure. The number of erythrocytes has significantly decrease after seven days of immersion at insecticide concentrations of 0.000625 ml Talstar/l water (bleak and perch and 0.00125 (prussian carp ml Talstar/l water. From the three investigated fish species, the perch proved to be the most sensitive to the action of the toxic substance, followed by the bleak and the prussian carp.

  6. Liénard-type models for the simulation of the action potential of cardiac nodal cells

    Science.gov (United States)

    Podziemski, P.; Żebrowski, J. J.

    2013-10-01

    Existing models of cardiac cells which include multi-variable cardiac transmembrane current are too complex to simulate the long time dynamical properties of the heart rhythm. The large number of parameters that need to be defined and set for such models make them not only cumbersome to use but also require a large computing power. Consequently, the application of such models for the bedside analysis of heart rate of a specific patient may be difficult. Other ways of modelling need to be investigated. We consider the general problem of developing a model of cardiac pacemaker tissue that allows to combine the investigation of phenomena at a time scale of thousands of heart beats with the ability to reproduce realistic tissue-level characteristics of cell dynamics. We propose a modified van der Pol-Duffing equation-a Liénard-type oscillator-as a phenomenological model for cardiac nodal tissue, with certain important physiological similarities to ion-channel models of cardiac pacemaker cells. The model presented here is specifically designed to qualitatively reproduce mesoscopic characteristics of cell dynamics, including action potential duration (APD) restitution properties, phase response characteristics, and phase space structure. We show that these characteristics agree qualitatively with the extensive ionic models and experimental results in the literature [Anumonwo et al., 1991, [33], Cao et al., 1999, [49], Coster and Celler, 2003, [31], Qu, 2004, [45], Tsalikakis et al., 2007, [32], Inada et al., 2009, [14], Qu et al., 2010, [50

  7. Calcium-activated chloride current determines action potential morphology during calcium alternans in atrial myocytes.

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    Kanaporis, Giedrius; Blatter, Lothar A

    2016-02-01

    Cardiac alternans--periodic beat-to-beat alternations in contraction, action potential (AP) morphology or cytosolic calcium transient (CaT) amplitude--is a high risk indicator for cardiac arrhythmias and sudden cardiac death. However, it remains an unresolved issue whether beat-to-beat alternations in intracellular Ca(2+) ([Ca(2+)]i ) or AP morphology are the primary cause of pro-arrhythmic alternans. Here we show that in atria AP alternans occurs secondary to CaT alternans. CaT alternans leads to complex beat-to-beat changes in Ca(2+)-regulated ion currents that determine alternans of AP morphology. We report the novel finding that alternans of AP morphology is largely sustained by the activity of Ca(2+)-activated Cl(-) channels (CaCCs). Suppression of the CaCCs significantly reduces AP alternans, while CaT alternans remains unaffected. The demonstration of a major role of CaCCs in the development of AP alternans opens new possibilities for atrial alternans and arrhythmia prevention. Cardiac alternans, described as periodic beat-to-beat alternations in contraction, action potential (AP) morphology or cytosolic Ca transient (CaT) amplitude, is a high risk indicator for cardiac arrhythmias and sudden cardiac death. We investigated mechanisms of cardiac alternans in single rabbit atrial myocytes. CaTs were monitored simultaneously with membrane currents or APs recorded with the patch clamp technique. Beat-to-beat alternations of AP morphology and CaT amplitude revealed a strong quantitative correlation. Application of voltage clamp protocols in the form of pre-recorded APs (AP-clamp) during pacing-induced CaT alternans revealed a Ca(2+)-dependent current consisting of a large outward component (4.78 ± 0.58 pA pF(-1) in amplitude) coinciding with AP phases 1 and 2 that was followed by an inward current (-0.42 ± 0.03 pA pF(-1); n = 21) during AP repolarization. Approximately 90% of the initial outward current was blocked by substitution of Cl(-) ions or application

  8. Mechanism of potassium efflux and action potential shortening during ischaemia in isolated mammalian cardiac muscle.

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    Gasser, R N; Vaughan-Jones, R D

    1990-12-01

    1. Ischaemia was simulated in the isolated sheep cardiac Purkinje fibre and guinea-pig papillary muscle by immersing the preparations in paraffin oil. Ion-selective microelectrodes recorded potassium (Ks+) and pH (pHs) in the thin film of Tyrode solution trapped at the fibre surface while other microelectrodes recorded intracellular pH (pHi), membrane potential and action potentials (AP) (evoked by field stimulation), or membrane current (two-microelectrode voltage clamp in shortened Purkinje fibres). Twitch tension was also monitored. The paraffin oil model reproduced the salient characteristics of myocardial ischaemia, i.e. a decrease of twitch tension; a decrease of pHi and pHs; a rise in Ks+ (by 2-3 mM); a depolarization of diastolic membrane potential; considerable shortening of the AP (up to 30% within 4 min). 2. The sulphonylurea compounds, glibenclamide (200 microM) and tolbutamide (1 mM), known inhibitors of the KATP channel, completely blocked the ischaemic rise of Ks+ and prevented AP shortening. Ischaemic tension decline was notably less pronounced in the presence of sulphonylureas. 3. The ischaemic increase of slope conductance (Purkinje fibre) was prevented by 1 mM-tolbutamide and 200 microM-glibenclamide. 4. Sulphonylureas did not affect resting membrane potential, the AP or the current-voltage relationship under non-ischaemic conditions (this also indicates that ischaemic Ks+ accumulation is not fuelled by the background K+ current [iK1] which was shown, as expected, to be Ba2+ sensitive). 5. In a normally perfused preparation, reducing intracellular ATP by inhibiting glycolysis with 2-deoxyglucose (DOG) produced a similar AP shortening plus a membrane hyperpolarization, both of which were inhibited by tolbutamide or glibenclamide. The AP shortening was not related uniquely to the fall of pHi observed under these conditions since experimentally reducing pHi (by reducing pHo in the absence of DOG) lengthened rather than shortened the AP. 6. The

  9. Bacteriocins: modes of action and potentials in food preservation and control of food poisoning.

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    Abee, T; Krockel, L; Hill, C

    1995-12-01

    Lactic acid bacteria (LAB) play an essential role in the majority of food fermentations, and a wide variety of strains are routinely employed as starter cultures in the manufacture of dairy, meat, vegetable and bakery products. One of the most important contributions of these microorganisms is the extended shelf life of the fermented product by comparison to that of the raw substrate. Growth of spoilage and pathogenic bacteria in these foods is inhibited due to competition for nutrients and the presence of starter-derived inhibitors such as lactic acid, hydrogen peroxide and bacteriocins (Ray and Daeschel, 1992). Bacteriocins, are a heterogenous group of anti-bacterial proteins that vary in spectrum of activity, mode of action, molecular weight, genetic origin and biochemical properties. Currently, artificial chemical preservatives are employed to limit the number of microorganisms capable of growing within foods, but increasing consumer awareness of potential health risks associated with some of these substances has led researchers to examine the possibility of using bacteriocins produced by LAB as biopreservatives. The major classes of bacteriocins produced by LAB include: (I) lantibiotics, (II) small heat stable peptides, (III) large heat labile proteins, and (IV) complex proteins whose activity requires the association of carbohydrate or lipid moieties (Klaenhammer, 1993). Significantly however, the inhibitory activity of these substances is confined to Gram-positive bacteria and inhibition of Gram-negatives by these bacteriocins has not been demonstrated, an observation which can be explained by a detailed analysis and comparison of the composition of Gram-positive and Gram-negative bacterial cell walls (Fig. 1). In both types the cytoplasmic membrane which forms the border between the cytoplasm and the external environment, is surrounded by a layer of peptidoglycan which is significantly thinner in Gram-negative bacteria than in Gram-positive bacteria. Gram

  10. Ventricular action potential adaptation to regular exercise: role of β-adrenergic and KATPchannel function.

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    Wang, Xinrui; Fitts, Robert H

    2017-08-01

    Regular exercise training is known to affect the action potential duration (APD) and improve heart function, but involvement of β-adrenergic receptor (β-AR) subtypes and/or the ATP-sensitive K + (K ATP ) channel is unknown. To address this, female and male Sprague-Dawley rats were randomly assigned to voluntary wheel-running or control groups; they were anesthetized after 6-8 wk of training, and myocytes were isolated. Exercise training significantly increased APD of apex and base myocytes at 1 Hz and decreased APD at 10 Hz. Ca 2+ transient durations reflected the changes in APD, while Ca 2+ transient amplitudes were unaffected by wheel running. The nonselective β-AR agonist isoproterenol shortened the myocyte APD, an effect reduced by wheel running. The isoproterenol-induced shortening of APD was largely reversed by the selective β 1 -AR blocker atenolol, but not the β 2 -AR blocker ICI 118,551, providing evidence that wheel running reduced the sensitivity of the β 1 -AR. At 10 Hz, the K ATP channel inhibitor glibenclamide prolonged the myocyte APD more in exercise-trained than control rats, implicating a role for this channel in the exercise-induced APD shortening at 10 Hz. A novel finding of this work was the dual importance of altered β 1 -AR responsiveness and K ATP channel function in the training-induced regulation of APD. Of physiological importance to the beating heart, the reduced response to adrenergic agonists would enhance cardiac contractility at resting rates, where sympathetic drive is low, by prolonging APD and Ca 2+ influx; during exercise, an increase in K ATP channel activity would shorten APD and, thus, protect the heart against Ca 2+ overload or inadequate filling. NEW & NOTEWORTHY Our data demonstrated that regular exercise prolonged the action potential and Ca 2+ transient durations in myocytes isolated from apex and base regions at 1-Hz and shortened both at 10-Hz stimulation. Novel findings were that wheel running shifted the

  11. Compound motor action potential duration and latency are markers of recurrent laryngeal nerve injury.

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    Bhatt, Neel K; Park, Andrea M; Al-Lozi, Mohammad T; Gale, Derrick C; Paniello, Randal C

    2017-08-01

    Compound motor action potential (CMAP) can quantitatively evaluate innervation following injury to the recurrent laryngeal nerve (RLN) in canines. CMAP duration (the total time of CMAP) and latency (the time between the nerve impulse and the onset of action potentials) have not been assessed following RLN injury. Animal study. Twelve canine hemilaryngeal preparations were investigated. Baseline CMAP duration and latency were derived. Group A (n = 5) underwent RLN stretch injury, and group B (n = 7) underwent RLN transection/repair. The change in CMAP duration and latency was assessed between the baseline and 6-month measurements using receiver operator characteristic (ROC) curves for each group individually and combined. Six months following injury, transection/repair injuries had the most significant increase in CMAP duration (2.8 ± 0.6 ms vs. 4.2 ± 0.8 ms, difference 1.4 ms 95% confidence interval [CI]: 0.43 to 2.40) and latency (2.6 ± 0.5 ms vs. 5.6 ± 1.5 ms, difference 3.0 ms 95% CI: 1.65 to 4.38). Stretch injuries also caused an increase in CMAP duration (2.3 ± 0.8 ms vs. 3.0 ± 0.6 ms, difference 0.7 ms 95% CI: -0.49 to 1.77) and latency (2.5 ± 0.8 ms vs. 4.7 ± 1.5 ms, difference 2.3 95% CI: 0.76 to 3.80). Using ROC curves, CMAP duration and latency differentiated between the baseline control and RLN injury at 6 months (area under the curve = 0.78 and 0.98, respectively). CMAP duration and latency are both quantitative measures that may have clinical utility as markers of RLN injury. CMAP latency had superior discrimination between injured and uninjured RLNs. Increased CMAP duration and latency may be explained by incomplete myelination and focal conduction block. NA. Laryngoscope, 127:1855-1860, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  12. Computational analysis of the human sinus node action potential: model development and effects of mutations.

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    Fabbri, Alan; Fantini, Matteo; Wilders, Ronald; Severi, Stefano

    2017-04-01

    We constructed a comprehensive mathematical model of the spontaneous electrical activity of a human sinoatrial node (SAN) pacemaker cell, starting from the recent Severi-DiFrancesco model of rabbit SAN cells. Our model is based on electrophysiological data from isolated human SAN pacemaker cells and closely matches the action potentials and calcium transient that were recorded experimentally. Simulated ion channelopathies explain the clinically observed changes in heart rate in corresponding mutation carriers, providing an independent qualitative validation of the model. The model shows that the modulatory role of the 'funny current' (I f ) in the pacing rate of human SAN pacemaker cells is highly similar to that of rabbit SAN cells, despite its considerably lower amplitude. The model may prove useful in the design of experiments and the development of heart-rate modulating drugs. The sinoatrial node (SAN) is the normal pacemaker of the mammalian heart.  Over several decades, a large amount of data on the ionic mechanisms underlying the spontaneous electrical activity of SAN pacemaker cells has been obtained, mostly in experiments on single cells isolated from rabbit SAN. This wealth of data has allowed the development of mathematical models of the electrical activity of rabbit SAN pacemaker cells. The present study aimed to construct a comprehensive model of the electrical activity of a human SAN pacemaker cell using recently obtained electrophysiological data from human SAN pacemaker cells.  We based our model on the recent Severi-DiFrancesco model of a rabbit SAN pacemaker cell. The action potential and calcium transient of the resulting model are close to the experimentally recorded values. The model has a much smaller 'funny current' (I f ) than do rabbit cells, although its modulatory role is highly similar. Changes in pacing rate upon the implementation of mutations associated with sinus node dysfunction agree with the clinical observations. This agreement

  13. Antinociceptive and anti-inflammatory potentials of kolaviron: mechanisms of action.

    Science.gov (United States)

    Onasanwo, Samuel A; Rotu, Rume A

    2016-06-01

    Major attention has been on dietary and medicinal phytochemicals that inhibit or reverse abnormal conditions caused by nociceptive and inflammatory stimuli. Garcinia kola (Guttiferae) seed, known as "bitter kola", plays an important role in African ethno-medicine and traditional hospitality like in the treatment of inflammation, colds, bronchitis, bacterial, and viral infections. A number of useful phytochemicals have been isolated from the seed, and the most prominent of them is kolaviron (Garcinia bioflavonoid), which has been suggested to have antinociceptive and anti-inflammatory potentials. The aim of this experiment is to explore the mechanisms of action of the antinociceptive and anti-inflammatory potentials of kolaviron. The probable mechanisms of action of kolaviron were assessed by using naloxone, prazosin, and atropine to investigate the involvement of adrenergic, opioidergic, and cholinergic systems, respectively, using tail flick, the acetic acid-induced writhing, formalin-induced paw licking, and carrageenan-induced paw edema models. Also, hematoxylin and eosin (H&E) staining was used to analyze the level of inflammation. In the acetic acid-induced writhing test in mice, pretreatment with naloxone, prazosin, and atropine significantly reversed the antinociception effects of kolaviron (200 mg/kg) when compared with control and kolaviron groups. In the formalin-induced paw licking test in mice, there was a significant decrease on the antinociceptive effects of kolaviron in the late phase when compared with the control, while the pretreatment with naloxone and prazosin significantly reversed the antinociception of kolaviron but atropine did not have any significant decrease when compared with the kolaviron group. In the tail flick latency assay in rats, pretreatment with naloxone and prazosin significantly reversed the antinociception of kolaviron but atropine; however, did not have any significant increase when compared with the control and kolaviron

  14. Biotic potential and reproductive parameters of Spodoptera dolichos (Lepidoptera: Noctuidae in the laboratory

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    Débora G. Montezano

    2015-12-01

    Full Text Available ABSTRACT The biotic potential and reproductive parameters of Spodoptera dolichos (Fabricius, 1794 were evaluated under controlled conditions (25 ± 1°C, 70 ± 10% RH and 14 hour photophase. The longevity, pre-, post- and oviposition periods, fecundity, and fertility of 25 couples were evaluated. The longevity of females (12.9 days was not significantly different than that of males (12.4 days. The mean durations of the pre-, post- and oviposition periods were 3.0, 0.4 and 10.4 days, respectively. The mean fecundity was 4,086.0 eggs per female and mean fertility was 3,557.8 larvae per female. On average, a female copulated 1.4 times. The biotic potential of S. dolichos was estimated at 7.138 x 1018 individuals/female/year. The net reproductive rate (Ro was 1,711.98 times per generation and the mean generation time (T was 56.19 days. The intrinsic rate of increase (rm was 0.133, with a finite rate of increase (l of 1.142 per day. These results are compared with other species from Spodoptera and their relevance for management strategies of S. dolichos.

  15. Motor Unit Number Estimation and Motor Unit Action Potential Analysis in Carpal Tunnel Syndrome

    Science.gov (United States)

    Sohn, Min Kyun; Jee, Sung Ju; Kim, Young-Jae; Shin, Hyun-Dae

    2011-01-01

    Objective To evaluate the clinical significance of motor unit number estimation (MUNE) and quantitative analysis of motor unit action potential (MUAP) in carpal tunnel syndrome (CTS) according to electrophysiologic severity, ultrasonographic measurement and clinical symptoms. Method We evaluated 78 wrists of 45 patients, who had been diagnosed with CTS and 42 wrists of 21 healthy controls. Median nerve conduction studies, amplitude and duration of MUAP, and the MUNE of the abductor pollicis brevis were measured. The cross sectional area (CSA) of the median nerve at the pisiform and distal radioulnar joint level was determined by high resolution ultrasonography. Clinical symptom of CTS was assessed using the Boston Carpal Tunnel Questionnaire (BCTQ). Results The MUNE, the amplitude and the duration of MUAP of the CTS group were significantly different from those found in the control group. The area under the ROC curve was 0.944 for MUNE, 0.923 for MUAP amplitude and 0.953 for MUAP duration. MUNE had a negative correlation with electrophysiologic stage of CTS, amplitude and duration of MUAP, CSA at pisiform level, and the score of BCTQ. The amplitude and duration of MUAP had a positive correlation with the score of BCTQ. The electrophysiologic stage was correlated with amplitude but not with the duration of MUAP. Conclusion MUNE, amplitude and duration of MUAP are useful tests for diagnosis of CTS. In addition, the MUNE serves as a good indicator of CTS severity. PMID:22506210

  16. A Hybrid Classifier for Characterizing Motor Unit Action Potentials in Diagnosing Neuromuscular Disorders

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    Kamali T

    2013-12-01

    Full Text Available Background: The time and frequency features of motor unit action potentials (MUAPs extracted from electromyographic (EMG signal provide discriminative information for diagnosis and treatment of neuromuscular disorders. However, the results of conventional automatic diagnosis methods using MUAP features is not convincing yet. Objective: The main goal in designing a MUAP characterization system is obtaining high classifcation accuracy to be used in clinical decision system. For this aim, in this study, a robust classifer is proposed to improve MUAP classifcation performance in estimating the class label (myopathic, neuropathic and normal of a given MUAP. Method: The proposed scheme employs both time and time–frequency features of a MUAP along with an ensemble of support vector machines (SVMs classifers in hybrid serial/parallel architecture. Time domain features includes phase, turn, peak to peak amplitude, area, and duration of the MUAP. Time–frequency features are discrete wavelet transform coeffcients of the MUAP. Results: Evaluation results of the developed system using EMG signals of 23 subjects (7 with myopathic, 8 with neuropathic and 8 with no diseases showed that the system estimated the class label of MUAPs extracted from these signals with average of accuracy of 91% which is at least 5% higher than the accuracy of two previously presented methods. Conclusion: Using different optimized subsets of features along with the presented hybrid classifer results in a classifcation accuracy that is encouraging to be used in clinical applications for MUAP characterization.

  17. Dendritic Properties Control Energy Efficiency of Action Potentials in Cortical Pyramidal Cells.

    Science.gov (United States)

    Yi, Guosheng; Wang, Jiang; Wei, Xile; Deng, Bin

    2017-01-01

    Neural computation is performed by transforming input signals into sequences of action potentials (APs), which is metabolically expensive and limited by the energy available to the brain. The metabolic efficiency of single AP has important consequences for the computational power of the cell, which is determined by its biophysical properties and morphologies. Here we adopt biophysically-based two-compartment models to investigate how dendrites affect energy efficiency of APs in cortical pyramidal neurons. We measure the Na + entry during the spike and examine how it is efficiently used for generating AP depolarization. We show that increasing the proportion of dendritic area or coupling conductance between two chambers decreases Na + entry efficiency of somatic AP. Activating inward Ca 2+ current in dendrites results in dendritic spike, which increases AP efficiency. Activating Ca 2+ -activated outward K + current in dendrites, however, decreases Na + entry efficiency. We demonstrate that the active and passive dendrites take effects by altering the overlap between Na + influx and internal current flowing from soma to dendrite. We explain a fundamental link between dendritic properties and AP efficiency, which is essential to interpret how neural computation consumes metabolic energy and how biophysics and morphologies contribute to such consumption.

  18. Calcium dependence of action potential-induced endocytosis in chromaffin cells.

    Science.gov (United States)

    Chan, Shyue-An; Chow, Robert; Smith, Corey

    2003-02-01

    Exocytosis occurs via fusion of transmitter-containing granules with the cell membrane, whereupon the granule contents are released and the cell membrane surface area increases. Exocytosis is followed by endocytosis to maintain proper cell membrane surface area and composition. We have shown that adrenal chromaffin cells internalize membrane in a biphasic manner following action potential stimulation. At basal firing rates (single - 0.5 Hz trains) endocytosis occurs by a rapid retrieval of membrane (termed Phase I) that is independent of the activity of the protein phosphatase calcineurin and wanes in efficiency with cell activity. At intermediate firing frequencies (>6 Hz) a second, calcineurin-sensitive, form of activity-enhanced endocytosis emerges (Phase II). In this study, we employ electrophysiological, electrochemical, and computational techniques to estimate intracellular Ca(2+) at the site of endocytosis by measuring secretion rates. The measured rates of secretion yield estimates of [Ca(2+)](i) based on a kinetic scheme for exocytosis calibrated under highly controlled [Ca(2+)](i). Based on this analysis, we propose that Phase I endocytosis is inhibited by cytosolic Ca(2+) with a K(inh)=605 nM, while Phase II endocytosis is activated by Ca(2+) with a K(act)=1.46 micro M. Molecular processes that may be consistent with the measured behaviors are discussed.

  19. Action potential propagation in transverse-axial tubular system is impaired in heart failure.

    Science.gov (United States)

    Sacconi, Leonardo; Ferrantini, Cecilia; Lotti, Jacopo; Coppini, Raffaele; Yan, Ping; Loew, Leslie M; Tesi, Chiara; Cerbai, Elisabetta; Poggesi, Corrado; Pavone, Francesco S

    2012-04-10

    The plasma membrane of cardiac myocytes presents complex invaginations known as the transverse-axial tubular system (TATS). Despite TATS's crucial role in excitation-contraction coupling and morphological alterations found in pathological settings, TATS's electrical activity has never been directly investigated in remodeled tubular networks. Here we develop an ultrafast random access multiphoton microscope that, in combination with a customly synthesized voltage-sensitive dye, is used to simultaneously measure action potentials (APs) at multiple sites within the sarcolemma with submillisecond temporal and submicrometer spatial resolution in real time. We find that the tight electrical coupling between different sarcolemmal domains is guaranteed only within an intact tubular system. In fact, acute detachment by osmotic shock of most tubules from the surface sarcolemma prevents AP propagation not only in the disconnected tubules, but also in some of the tubules that remain connected with the surface. This indicates that a structural disorganization of the tubular system worsens the electrical coupling between the TATS and the surface. The pathological implications of this finding are investigated in failing hearts. We find that AP propagation into the pathologically remodeled TATS frequently fails and may be followed by local spontaneous electrical activity. Our findings provide insight on the relationship between abnormal TATS and asynchronous calcium release, a major determinant of cardiac contractile dysfunction and arrhythmias.

  20. The transformative potential of action research and ICT in the Second Language (L2 classroom

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    Farren Margaret

    2015-12-01

    Full Text Available This study shows the transformative potential of action research and information and communications technology (ICT in the second language (L2 classroom. Two enquiries from teacher-researchers are detailed in the article. Their engagement in a collaborative professional development Masters programme was pivotal in designing and implementing ICT creatively in their classroom. Gee (2008 advocates the use of the preferred media of our classroom students in order to address their learning. Prensky (2001 urges us to feel the fear and do it anyway with our digital native classes. A post-primary teacher and a primary teacher show us how they felt the fear, did it and transformed aspects of their own teaching in the process. The Masters programme required the teachers to engage with innovative practices, informed by their own values, and integrate technologies that were new to them into their repertoire of classroom strategies. Peer validation meetings with colleagues enabled meaningful insights to emerge from the research. The teachers improve and transform their second language (L2 practice in collaboration and validation with others.

  1. Action potential generation at an AIS-like process in the axonless retinal AII amacrine cell

    Science.gov (United States)

    Wu, Chaowen; Ivanova, Elena; Cui, Jinjuan; Lu, Qi; Pan, Zhuo-Hua

    2011-01-01

    In axon-bearing neurons, action potentials conventionally initiate at the axon initial segment (AIS) and are important for neuron excitability and cell-to-cell communication. However in axonless neurons, spike origin has remained unclear. Here we report in the axonless spiking AII amacrine cell of the mouse retina a dendritic process sharing organizational and functional similarities with the AIS. This process was revealed through viral-mediated expression of channelrhodopsin-2-GFP (ChR2-GFP) with the AIS-targeting motif of sodium channels (NavII-III). The AII-processes showed clustering of voltage-gated Na+ channel 1.1 (Nav1.1) as well as AIS markers ankyrin-G and neurofascin. Furthermore, NavII-III targeting disrupted Nav1.1 clustering in the AII-process which drastically decreased Na+ current and abolished the ability of the AII amacrine cell to generate spiking. Our findings indicate that despite lacking an axon, spiking in the axonless neuron can originate at a specialized AIS-like process. PMID:21994381

  2. Action potential energy efficiency varies among neuron types in vertebrates and invertebrates.

    Directory of Open Access Journals (Sweden)

    Biswa Sengupta

    2010-07-01

    Full Text Available The initiation and propagation of action potentials (APs places high demands on the energetic resources of neural tissue. Each AP forces ATP-driven ion pumps to work harder to restore the ionic concentration gradients, thus consuming more energy. Here, we ask whether the ionic currents underlying the AP can be predicted theoretically from the principle of minimum energy consumption. A long-held supposition that APs are energetically wasteful, based on theoretical analysis of the squid giant axon AP, has recently been overturned by studies that measured the currents contributing to the AP in several mammalian neurons. In the single compartment models studied here, AP energy consumption varies greatly among vertebrate and invertebrate neurons, with several mammalian neuron models using close to the capacitive minimum of energy needed. Strikingly, energy consumption can increase by more than ten-fold simply by changing the overlap of the Na(+ and K(+ currents during the AP without changing the APs shape. As a consequence, the height and width of the AP are poor predictors of energy consumption. In the Hodgkin-Huxley model of the squid axon, optimizing the kinetics or number of Na(+ and K(+ channels can whittle down the number of ATP molecules needed for each AP by a factor of four. In contrast to the squid AP, the temporal profile of the currents underlying APs of some mammalian neurons are nearly perfectly matched to the optimized properties of ionic conductances so as to minimize the ATP cost.

  3. Action potential simulation (APS) in patients with fibromyalgia syndrome (FMS): a controlled single subject experimental design.

    Science.gov (United States)

    Fengler, R K B; Jacobs, J W G; Bac, M; van Wijck, A J M; van Meeteren, N L U

    2007-03-01

    Action potential simulation (APS) is becoming a popular method of pain reduction. Nevertheless, little is known about the efficacy of this relatively new treatment. The aim of this study was to investigate whether APS helps to reduce pain, improves patients' perception of daily functioning and social participation in patients with fibromyalgia syndrome (FMS). Ten patients with FMS according to the American College of Rheumatology (ACR) criteria entered this double blind crossover single-case study. In a period of 20 weeks, the patients underwent two treatment periods of 4 weeks, one with verum and one with placebo, at random, in a double blind fashion. Outcome measures were evaluated on a weekly basis. Primary outcome measure was pain measured with the Fibromyalgia Impact Questionnaire (FIQ) questions 4 and 5, the number of tender points and the total tender point pain intensity score. Both visual inspection and statistical analysis were done to analyse the data from this single-subject design. Performing visual inspection and statistical analysis, no positive results of the APS treatment were found in this study. Remarkable is the fact that placebo APS had significantly better results than verum APS. In this single-case study with ten patients (all female), APS was not a helpful method to reduce pain, to improve patients' perception of daily functioning and social participation in patients with FMS.

  4. Covariation of axon initial segment location and dendritic tree normalizes the somatic action potential.

    Science.gov (United States)

    Hamada, Mustafa S; Goethals, Sarah; de Vries, Sharon I; Brette, Romain; Kole, Maarten H P

    2016-12-20

    In mammalian neurons, the axon initial segment (AIS) electrically connects the somatodendritic compartment with the axon and converts the incoming synaptic voltage changes into a temporally precise action potential (AP) output code. Although axons often emanate directly from the soma, they may also originate more distally from a dendrite, the implications of which are not well-understood. Here, we show that one-third of the thick-tufted layer 5 pyramidal neurons have an axon originating from a dendrite and are characterized by a reduced dendritic complexity and thinner main apical dendrite. Unexpectedly, the rising phase of somatic APs is electrically indistinguishable between neurons with a somatic or a dendritic axon origin. Cable analysis of the neurons indicated that the axonal axial current is inversely proportional to the AIS distance, denoting the path length between the soma and the start of the AIS, and to produce invariant somatic APs, it must scale with the local somatodendritic capacitance. In agreement, AIS distance inversely correlates with the apical dendrite diameter, and model simulations confirmed that the covariation suffices to normalize the somatic AP waveform. Therefore, in pyramidal neurons, the AIS location is finely tuned with the somatodendritic capacitive load, serving as a homeostatic regulation of the somatic AP in the face of diverse neuronal morphologies.

  5. Loss of Saltation and Presynaptic Action Potential Failure in Demyelinated Axons.

    Science.gov (United States)

    Hamada, Mustafa S; Popovic, Marko A; Kole, Maarten H P

    2017-01-01

    In cortical pyramidal neurons the presynaptic terminals controlling transmitter release are located along unmyelinated axon collaterals, far from the original action potential (AP) initiation site, the axon initial segment (AIS). Once initiated, APs will need to reliably propagate over long distances and regions of geometrical inhomogeneity like branch points (BPs) to rapidly depolarize the presynaptic terminals and confer temporally precise synaptic transmission. While axon pathologies such as demyelinating diseases are well established to impede the fidelity of AP propagation along internodes, to which extent myelin loss affects propagation along BPs and axon collaterals is not well understood. Here, using the cuprizone demyelination model, we performed optical voltage-sensitive dye (VSD) imaging from control and demyelinated layer 5 pyramidal neuron axons. In the main axon, we find that myelin loss switches the modality of AP propagation from rapid saltation towards a slow continuous wave. The duration of single AP waveforms at BPs or nodes was, however, only slightly briefer. In contrast, by using two-photon microscopy-guided loose-seal patch recordings from axon collaterals we revealed a presynaptic AP broadening in combination with a reduced velocity and frequency-dependent failure. Finally, internodal myelin loss was also associated with de novo sprouting of axon collaterals starting from the primary (demyelinated) axon. Thus, the loss of oligodendrocytes and myelin sheaths bears functional consequences beyond the main axon, impeding the temporal fidelity of presynaptic APs and affecting the functional and structural organization of synaptic connectivity within the neocortex.

  6. Altered Chloride Homeostasis Decreases the Action Potential Threshold and Increases Hyperexcitability in Hippocampal Neurons.

    Science.gov (United States)

    Sørensen, Andreas T; Ledri, Marco; Melis, Miriam; Nikitidou Ledri, Litsa; Andersson, My; Kokaia, Merab

    2017-01-01

    Chloride ions play an important role in controlling excitability of principal neurons in the central nervous system. When neurotransmitter GABA is released from inhibitory interneurons, activated GABA type A (GABA A ) receptors on principal neurons become permeable to chloride. Typically, chloride flows through activated GABA A receptors into the neurons causing hyperpolarization or shunting inhibition, and in turn inhibits action potential (AP) generation. However, in situations when intracellular chloride concentration is increased, chloride ions can flow in opposite direction, depolarize neurons, and promote AP generation. It is generally recognized that altered chloride homeostasis per se has no effect on the AP threshold. Here, we demonstrate that chloride overload of mouse principal CA3 pyramidal neurons not only makes these cells more excitable through GABA A receptor activation but also lowers the AP threshold, further aggravating excitability. This phenomenon has not been described in principal neurons and adds to our understanding of mechanisms regulating neuronal and network excitability, particularly in developing brain and during pathological situations with altered chloride homeostasis. This finding further broadens the spectrum of neuronal plasticity regulated by ionic compositions across the cellular membrane.

  7. Correlates of a single cortical action potential in the epidural EEG

    Science.gov (United States)

    Teleńczuk, Bartosz; Baker, Stuart N; Kempter, Richard; Curio, Gabriel

    2015-01-01

    To identify the correlates of a single cortical action potential in surface EEG, we recorded simultaneously epidural EEG and single-unit activity in the primary somatosensory cortex of awake macaque monkeys. By averaging over EEG segments coincident with more than hundred thousand single spikes, we found short-lived (≈ 0.5 ms) triphasic EEG deflections dominated by high-frequency components > 800 Hz. The peak-to-peak amplitude of the grand-averaged spike correlate was 80 nV, which matched theoretical predictions, while single-neuron amplitudes ranged from 12 to 966 nV. Combining these estimates with post-stimulus-time histograms of single-unit responses to median-nerve stimulation allowed us to predict the shape of the evoked epidural EEG response and to estimate the number of contributing neurons. These findings establish spiking activity of cortical neurons as a primary building block of high-frequency epidural EEG, which thus can serve as a quantitative macroscopic marker of neuronal spikes. PMID:25554430

  8. An overview of skin penetration enhancers: penetration enhancing activity, skin irritation potential and mechanism of action

    Directory of Open Access Journals (Sweden)

    Sarunyoo Songkro

    2009-08-01

    Full Text Available Transdermal drug delivery has attracted considerable attention over the past 2-3 decades in regard of its many potentialadvantages. However, the role of the skin as a protective barrier renders skin absorption of most drugs problematic. Therefore,skin penetration enhancers are frequently used in the field of transdermal drug delivery in order to reversibly reduce thebarrier function of the stratum corneum, the outermost layer of the skin. To date, a wide range of chemical compounds havebeen shown to enhance the skin penetration of therapeutic drugs. This review presents a critical account of the most commonlyused chemical penetration enhancers (fatty acids and surfactants, and some newer classes of chemical enhancers (terpenes,polymers, monoolein, oxazolidinones, with emphasis on their efficacy, mechanism of action, and skin irritation potential. Thisreview also discusses the traditional and more recently developed methods for the screening and evaluation of chemical penetration enhancers, and addresses the continuing problems in the rational selection of a chemical penetration enhancer for a specific drug to be delivered via the transdermal route.

  9. Effects of stochastic channel gating and distribution on the cardiac action potential.

    Science.gov (United States)

    Lemay, Mathieu; de Lange, Enno; Kucera, Jan P

    2011-07-21

    Ion channels exhibit stochastic conformational changes determining their gating behavior. In addition, the process of protein turnover leads to a natural variability of the number of membrane and gap junctional channels. Nevertheless, in computational models, these two aspects are scarcely considered and their impacts are largely unknown. We investigated the effects of stochastic current fluctuations and channel distributions on action potential duration (APD), intercellular conduction delays (ICDs) and conduction blocks using a modified ventricular cell model (Rudy et al.) with Markovian formulations of the principal ion currents (to simulate their stochastic open-close gating behavior) and with channel counts drawn from Poisson distributions (to simulate their natural variability). In single cells, APD variability (coefficient of variation: 1.6% at BCL=1000ms) was essentially caused by stochastic channel gating of I(Ks), persistent I(Na) and I(Ca,L). In cell strands, ICD variability induced by stochastic channel gating and Poissonian channel distributions was low under normal conditions. Nonetheless, at low intercellular coupling levels, Poissonian gap junctional channel distribution resulted in a large ICD variability (coefficient of variation >20%), highly heterogeneous conduction patterns and conduction blocks. Therefore, the stochastic behavior of current fluctuations and channel distributions can contribute to the heterogeneity of conduction patterns and to conduction block, as observed previously in experiments in cardiac tissue with altered intercellular coupling. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Dendritic Properties Control Energy Efficiency of Action Potentials in Cortical Pyramidal Cells

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    Guosheng Yi

    2017-09-01

    Full Text Available Neural computation is performed by transforming input signals into sequences of action potentials (APs, which is metabolically expensive and limited by the energy available to the brain. The metabolic efficiency of single AP has important consequences for the computational power of the cell, which is determined by its biophysical properties and morphologies. Here we adopt biophysically-based two-compartment models to investigate how dendrites affect energy efficiency of APs in cortical pyramidal neurons. We measure the Na+ entry during the spike and examine how it is efficiently used for generating AP depolarization. We show that increasing the proportion of dendritic area or coupling conductance between two chambers decreases Na+ entry efficiency of somatic AP. Activating inward Ca2+ current in dendrites results in dendritic spike, which increases AP efficiency. Activating Ca2+-activated outward K+ current in dendrites, however, decreases Na+ entry efficiency. We demonstrate that the active and passive dendrites take effects by altering the overlap between Na+ influx and internal current flowing from soma to dendrite. We explain a fundamental link between dendritic properties and AP efficiency, which is essential to interpret how neural computation consumes metabolic energy and how biophysics and morphologies contribute to such consumption.

  11. Adhesion to carbon nanotube conductive scaffolds forces action-potential appearance in immature rat spinal neurons.

    Directory of Open Access Journals (Sweden)

    Alessandra Fabbro

    Full Text Available In the last decade, carbon nanotube growth substrates have been used to investigate neurons and neuronal networks formation in vitro when guided by artificial nano-scaled cues. Besides, nanotube-based interfaces are being developed, such as prosthesis for monitoring brain activity. We recently described how carbon nanotube substrates alter the electrophysiological and synaptic responses of hippocampal neurons in culture. This observation highlighted the exceptional ability of this material in interfering with nerve tissue growth. Here we test the hypothesis that carbon nanotube scaffolds promote the development of immature neurons isolated from the neonatal rat spinal cord, and maintained in vitro. To address this issue we performed electrophysiological studies associated to gene expression analysis. Our results indicate that spinal neurons plated on electro-conductive carbon nanotubes show a facilitated development. Spinal neurons anticipate the expression of functional markers of maturation, such as the generation of voltage dependent currents or action potentials. These changes are accompanied by a selective modulation of gene expression, involving neuronal and non-neuronal components. Our microarray experiments suggest that carbon nanotube platforms trigger reparative activities involving microglia, in the absence of reactive gliosis. Hence, future tissue scaffolds blended with conductive nanotubes may be exploited to promote cell differentiation and reparative pathways in neural regeneration strategies.

  12. Decline of compound muscle action potentials and statistical MUNEs during Wallerian degeneration.

    Science.gov (United States)

    Unlusoy Acar, Z; Yalinay Dikmen, P; Yayla, V; Başaran, K; Emekli, U; Öge, A E

    2014-09-01

    In two previous studies, we found that the compound muscle action potential (CMAP) amplitude loss was significantly higher than the loss of estimated motor unit numbers in the course of Wallerian degeneration (WD). In order to overcome some drawbacks of the method previously used, we performed a similar CMAP vs MUNE comparison by using the statistical motor unit number estimation (MUNE) method. Initial electrophysiological studies on 6 patients were performed between 22 and 98 hours after the injuries; it was possible to make repeated examinations, four times in 1 nerve, twice in 1 nerve and three times in 4 nerves, before the eventual complete disappearance of the CMAPs. The transected/intact (T/I) side CMAP ratios declined steeply as WD evolved. They were significantly lower than the relatively stable MUNE ratios 48 hours after the injury. This study, performed with the use of statistical MUNE, strengthens our previous observation by the incremental method that might have some relevance to the pathophysiology of early WD. CMAP amplitude loss that is more than expected from the amount of axonal degeneration may indicate a considerable amount of inactive muscle fibers in the motor units innervated by the nerve fibers, which are undergoing degeneration but still retain their excitability. Although technical sources of error cannot be totally excluded, our findings could more likely be explained by the failing of neuromuscular synapses in an asynchronous order before complete unresponsiveness of the motor unit ensues. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  13. Multifocal fluorescence microscope for fast optical recordings of neuronal action potentials.

    Science.gov (United States)

    Shtrahman, Matthew; Aharoni, Daniel B; Hardy, Nicholas F; Buonomano, Dean V; Arisaka, Katsushi; Otis, Thomas S

    2015-02-03

    In recent years, optical sensors for tracking neural activity have been developed and offer great utility. However, developing microscopy techniques that have several kHz bandwidth necessary to reliably capture optically reported action potentials (APs) at multiple locations in parallel remains a significant challenge. To our knowledge, we describe a novel microscope optimized to measure spatially distributed optical signals with submillisecond and near diffraction-limit resolution. Our design uses a spatial light modulator to generate patterned illumination to simultaneously excite multiple user-defined targets. A galvanometer driven mirror in the emission path streaks the fluorescence emanating from each excitation point during the camera exposure, using unused camera pixels to capture time varying fluorescence at rates that are ∼1000 times faster than the camera's native frame rate. We demonstrate that this approach is capable of recording Ca(2+) transients resulting from APs in neurons labeled with the Ca(2+) sensor Oregon Green Bapta-1 (OGB-1), and can localize the timing of these events with millisecond resolution. Furthermore, optically reported APs can be detected with the voltage sensitive dye DiO-DPA in multiple locations within a neuron with a signal/noise ratio up to ∼40, resolving delays in arrival time along dendrites. Thus, the microscope provides a powerful tool for photometric measurements of dynamics requiring submillisecond sampling at multiple locations. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  14. Benefits of Nut Consumption on Insulin Resistance and Cardiovascular Risk Factors: Multiple Potential Mechanisms of Actions

    Directory of Open Access Journals (Sweden)

    Yoona Kim

    2017-11-01

    Full Text Available Epidemiological and clinical studies have indicated that nut consumption could be a healthy dietary strategy to prevent and treat type 2 diabetes (T2DM and related cardiovascular disease (CVD. The objective of this review is to examine the potential mechanisms of action of nuts addressing effects on glycemic control, weight management, energy balance, appetite, gut microbiota modification, lipid metabolism, oxidative stress, inflammation, endothelial function and blood pressure with a focus on data from both animal and human studies. The favourable effects of nuts could be explained by the unique nutrient composition and bioactive compounds in nuts. Unsaturated fatty acids (monounsaturated fatty acids and polyunsaturated fatty acids present in nuts may play a role in glucose control and appetite suppression. Fiber and polyphenols in nuts may also have an anti-diabetic effect by altering gut microbiota. Nuts lower serum cholesterol by reduced cholesterol absorption, inhibition of HMG-CoA reductase and increased bile acid production by stimulation of 7-α hydroxylase. Arginine and magnesium improve inflammation, oxidative stress, endothelial function and blood pressure. In conclusion, nuts contain compounds that favourably influence glucose homeostasis, weight control and vascular health. Further investigations are required to identify the most important mechanisms by which nuts decrease the risk of T2DM and CVD.

  15. Effects of terpineol on the compound action potential of the rat sciatic nerve

    Directory of Open Access Journals (Sweden)

    M.R. Moreira

    2001-10-01

    Full Text Available Terpineol, a volatile terpenoid alcohol of low toxicity, is widely used in the perfumery industry. It is an important chemical constituent of the essential oil of many plants with widespread applications in folk medicine and in aromatherapy. The effects of terpineol on the compound action potential (CAP of rat sciatic nerve were studied. Terpineol induced a dose-dependent blockade of the CAP. At 100 µM, terpineol had no demonstrable effect. At 300 µM terpineol, peak-to-peak amplitude and conduction velocity of CAP were significantly reduced at the end of 180-min exposure of the nerve to the drug, from 3.28 ± 0.22 mV and 33.5 ± 7.05 m/s, respectively, to 1.91 ± 0.51 mV and 26.2 ± 4.55 m/s. At 600 µM, terpineol significantly reduced peak-to-peak amplitude and conduction velocity from 2.97 ± 0.55 mV and 32.8 ± 3.91 m/s to 0.24 ± 0.23 mV and 2.72 ± 2.72 m/s, respectively (N = 5. All these effects developed slowly and were reversible upon 180-min washout.

  16. Adhesion to carbon nanotube conductive scaffolds forces action-potential appearance in immature rat spinal neurons.

    Science.gov (United States)

    Fabbro, Alessandra; Sucapane, Antonietta; Toma, Francesca Maria; Calura, Enrica; Rizzetto, Lisa; Carrieri, Claudia; Roncaglia, Paola; Martinelli, Valentina; Scaini, Denis; Masten, Lara; Turco, Antonio; Gustincich, Stefano; Prato, Maurizio; Ballerini, Laura

    2013-01-01

    In the last decade, carbon nanotube growth substrates have been used to investigate neurons and neuronal networks formation in vitro when guided by artificial nano-scaled cues. Besides, nanotube-based interfaces are being developed, such as prosthesis for monitoring brain activity. We recently described how carbon nanotube substrates alter the electrophysiological and synaptic responses of hippocampal neurons in culture. This observation highlighted the exceptional ability of this material in interfering with nerve tissue growth. Here we test the hypothesis that carbon nanotube scaffolds promote the development of immature neurons isolated from the neonatal rat spinal cord, and maintained in vitro. To address this issue we performed electrophysiological studies associated to gene expression analysis. Our results indicate that spinal neurons plated on electro-conductive carbon nanotubes show a facilitated development. Spinal neurons anticipate the expression of functional markers of maturation, such as the generation of voltage dependent currents or action potentials. These changes are accompanied by a selective modulation of gene expression, involving neuronal and non-neuronal components. Our microarray experiments suggest that carbon nanotube platforms trigger reparative activities involving microglia, in the absence of reactive gliosis. Hence, future tissue scaffolds blended with conductive nanotubes may be exploited to promote cell differentiation and reparative pathways in neural regeneration strategies.

  17. Improved health and growth of fish fed mannan oligosaccharides: potential mode of action.

    Science.gov (United States)

    Torrecillas, Silvia; Montero, Daniel; Izquierdo, Marisol

    2014-02-01

    Nowadays, aquaculture industry still confronts several disease-related problems mainly caused by viruses, bacteria and parasites. In the last decade, the use of mannan oligosaccharides (MOS) in fish production has received increased attention due to its beneficial effects on fish performance and disease resistance. This review shows the MOS use in aquaculture with a specific emphasis on the effectiveness of the several MOS forms available in the market related to disease resistance, fish nutrition and the possible mechanisms involved. Among the main beneficial effects attributed to MOS dietary supplementation, enhanced fish performance, feed efficiency and pathogen protection by potentiation of the systemic and local immune system and the reinforcement of the epithelial barrier structure and functionality are some of the most commonly demonstrated benefits. These combined effects suggest that the reinforcement of the intestinal integrity and functionality, together with the stimulation of the innate immune system, are the primary mode of action of MOS in fish. However, the supplementation strategy related to the structure of the MOS added, the correct dose and duration, as well as fish species, size and culture conditions are determinant factors to achieve improvements in health status and growth performance. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Do Resin Cements Alter Action Potentials of Isolated Rat Sciatic Nerve?

    Science.gov (United States)

    Ertan, Ahmet Atila; Beriat, Nilufer Celebi; Onur, Mehmet Ali; Tan, Gamze; Cehreli, Murat Cavit

    2011-01-01

    Objectives: The purpose of this study was to explore the effects dual-cure resin cements on nerve conduction. Methods: Panavia F, RelyX ARC, and Variolink II polymerized either by light-emitting diode (LED) or quartz tungsten halogen (QTH) were used in the study (n=10). The conductance of sciatic nerves of 50 rats were measured before and after contact with the specimens for 1 h. Results: The time-dependent change in nerve conductance and the comparison of LED versus QTH showed that differences between groups are significant (P<.05). For both polymerization techniques, pair-wise comparisons of resin cements showed that the nerve conductance between groups is different (P<.05). RelyX ARC elicited irreversible inhibition of compound action potentials (more than 50% change) and Panavia F and Variolink II polymerized by LED and QTH did not alter nerve conduction beyond physiologic limits. Conclusions: Resin cements may alter nerve conductance and even lead to neurotoxic effects. PMID:21494389

  19. MCH and apomorphine in combination enhance action potential firing of nucleus accumbens shell neurons in vitro

    Directory of Open Access Journals (Sweden)

    F Woodward Hopf

    2013-04-01

    Full Text Available The MCH and dopamine receptor systems have been shown to modulate a number of behaviors related to reward processing, addiction, and neuropsychiatric conditions such as schizophrenia and depression. In addition, MCH and dopamine receptors can interact in a positive manner, for example in the expression of cocaine self-administration. A recent report (Chung et al., 2011a showed that the DA1/DA2 dopamine receptor activator apomorphine suppresses pre-pulse inhibition, a preclinical model for some aspects of schizophrenia. Importantly, MCH can enhance the effects of lower doses of apomorphine, suggesting that co-modulation of dopamine and MCH receptors might alleviate some symptoms of schizophrenia with a lower dose of dopamine receptor modulator and thus fewer potential side effects. Here, we investigated whether MCH and apomorphine could enhance action potential firing in vitro in the nucleus accumbens shell (NAshell, a region which has previously been shown to mediate some behavioral effects of MCH. Using whole-cell patch-clamp electrophysiology, we found that MCH, which has no effect on firing on its own, was able to increase NAshell firing when combined with a subthreshold dose of apomorphine. Further, this MCH/apomorphine increase in firing was prevented by an antagonist of either a DA1 or a DA2 receptor, suggesting that apomorphine acts through both receptor types to enhance NAshell firing. The MCH/apomorphine-mediated firing increase was also prevented by an MCH receptor antagonist or a PKA inhibitor. Taken together, our results suggest that MCH can interact with lower doses of apomorphine to enhance NAshell firing, and thus that MCH and apomorphine might interact in vivo within the NAshell to suppress pre-pulse inhibition.

  20. Burst analysis tool for developing neuronal networks exhibiting highly varying action potential dynamics

    Directory of Open Access Journals (Sweden)

    Fikret Emre eKapucu

    2012-06-01

    Full Text Available In this paper we propose a firing statistics based neuronal network burst detection algorithm for neuronal networks exhibiting highly variable action potential dynamics. Electrical activity of neuronal networks is generally analyzed by the occurrences of spikes and bursts both in time and space. Commonly accepted analysis tools employ burst detection algorithms based on predefined criteria. However, maturing neuronal networks, such as those originating from human embryonic stem cells (hESC, exhibit highly variable network structure and time-varying dynamics. To explore the developing burst/spike activities of such networks, we propose a burst detection algorithm which utilizes the firing statistics based on interspike interval (ISI histograms. Moreover, the algorithm calculates interspike interval thresholds for burst spikes as well as for pre-burst spikes and burst tails by evaluating the cumulative moving average and skewness of the ISI histogram. Because of the adaptive nature of the proposed algorithm, its analysis power is not limited by the type of neuronal cell network at hand. We demonstrate the functionality of our algorithm with two different types of microelectrode array (MEA data recorded from spontaneously active hESC-derived neuronal cell networks. The same data was also analyzed by two commonly employed burst detection algorithms and the differences in burst detection results are illustrated. The results demonstrate that our method is both adaptive to the firing statistics of the network and yields successful burst detection from the data. In conclusion, the proposed method is a potential tool for analyzing of hESC-derived neuronal cell networks and thus can be utilized in studies aiming to understand the development and functioning of human neuronal networks and as an analysis tool for in vitro drug screening and neurotoxicity assays.

  1. Action Potential Shortening and Impairment of Cardiac Function by Ablation ofSlc26a6.

    Science.gov (United States)

    Sirish, Padmini; Ledford, Hannah A; Timofeyev, Valeriy; Thai, Phung N; Ren, Lu; Kim, Hyo Jeong; Park, Seojin; Lee, Jeong Han; Dai, Gu; Moshref, Maryam; Sihn, Choong-Ryoul; Chen, Wei Chun; Timofeyeva, Maria Valeryevna; Jian, Zhong; Shimkunas, Rafael; Izu, Leighton T; Chiamvimonvat, Nipavan; Chen-Izu, Ye; Yamoah, Ebenezer N; Zhang, Xiao-Dong

    2017-10-01

    Intracellular pH (pH i ) is critical to cardiac excitation and contraction; uncompensated changes in pH i impair cardiac function and trigger arrhythmia. Several ion transporters participate in cardiac pH i regulation. Our previous studies identified several isoforms of a solute carrier Slc26a6 to be highly expressed in cardiomyocytes. We show that Slc26a6 mediates electrogenic Cl - /HCO 3 - exchange activities in cardiomyocytes, suggesting the potential role of Slc26a6 in regulation of not only pH i , but also cardiac excitability. To test the mechanistic role of Slc26a6 in the heart, we took advantage of Slc26a6 knockout ( Slc26a6 -/ - ) mice using both in vivo and in vitro analyses. Consistent with our prediction of its electrogenic activities, ablation of Slc26a6 results in action potential shortening. There are reduced Ca 2+ transient and sarcoplasmic reticulum Ca 2+ load, together with decreased sarcomere shortening in Slc26a6 -/ - cardiomyocytes. These abnormalities translate into reduced fractional shortening and cardiac contractility at the in vivo level. Additionally, pH i is elevated in Slc26a6 -/ - cardiomyocytes with slower recovery kinetics from intracellular alkalization, consistent with the Cl - /HCO 3 - exchange activities of Slc26a6. Moreover, Slc26a6 -/ - mice show evidence of sinus bradycardia and fragmented QRS complex, supporting the critical role of Slc26a6 in cardiac conduction system. Our study provides mechanistic insights into Slc26a6, a unique cardiac electrogenic Cl - /HCO 3 - transporter in ventricular myocytes, linking the critical roles of Slc26a6 in regulation of pH i , excitability, and contractility. pH i is a critical regulator of other membrane and contractile proteins. Future studies are needed to investigate possible changes in these proteins in Slc26a6 -/ - mice. © 2017 American Heart Association, Inc.

  2. Small-Molecule Inhibitors of Pendrin Potentiate the Diuretic Action of Furosemide

    Science.gov (United States)

    Cil, Onur; Haggie, Peter M.; Phuan, Puay-wah; Tan, Joseph-Anthony

    2016-01-01

    Pendrin is a Cl−/HCO3− exchanger expressed in type B and non-A, non-B intercalated cells in the distal nephron, where it facilitates Cl− absorption and is involved in Na+ absorption and acid-base balance. Pendrin-knockout mice show no fluid-electrolyte abnormalities under baseline conditions, although mice with double knockout of pendrin and the Na+/Cl− cotransporter (NCC) manifest profound salt wasting. Thus, pendrin may attenuate diuretic-induced salt loss, but this function remains unconfirmed. To clarify the physiologic role of pendrin under conditions not confounded by gene knockout, and to test the potential utility of pendrin inhibitors for diuretic therapy, we tested in mice a small-molecule pendrin inhibitor identified from a high-throughput screen. In vitro, a pyrazole-thiophenesulfonamide, PDSinh-C01, inhibited Cl−/anion exchange mediated by mouse pendrin with a 50% inhibitory concentration of 1–3 µM, without affecting other major kidney tubule transporters. Administration of PDSinh-C01 to mice at predicted therapeutic doses, determined from serum and urine pharmacokinetics, did not affect urine output, osmolality, salt excretion, or acid-base balance. However, in mice treated acutely with furosemide, administration of PDSinh-C01 produced a 30% increase in urine output, with increased Na+ and Cl− excretion. In mice treated long term with furosemide, in which renal pendrin is upregulated, PDSinh-C01 produced a 60% increase in urine output. Our findings clarify the role of pendrin in kidney function and suggest pendrin inhibition as a novel approach to potentiate the action of loop diuretics. Such combination therapy might enhance diuresis and salt excretion for treatment of hypertension and edema, perhaps including diuretic-resistant edema. PMID:27153921

  3. Burst analysis tool for developing neuronal networks exhibiting highly varying action potential dynamics.

    Science.gov (United States)

    Kapucu, Fikret E; Tanskanen, Jarno M A; Mikkonen, Jarno E; Ylä-Outinen, Laura; Narkilahti, Susanna; Hyttinen, Jari A K

    2012-01-01

    In this paper we propose a firing statistics based neuronal network burst detection algorithm for neuronal networks exhibiting highly variable action potential dynamics. Electrical activity of neuronal networks is generally analyzed by the occurrences of spikes and bursts both in time and space. Commonly accepted analysis tools employ burst detection algorithms based on predefined criteria. However, maturing neuronal networks, such as those originating from human embryonic stem cells (hESCs), exhibit highly variable network structure and time-varying dynamics. To explore the developing burst/spike activities of such networks, we propose a burst detection algorithm which utilizes the firing statistics based on interspike interval (ISI) histograms. Moreover, the algorithm calculates ISI thresholds for burst spikes as well as for pre-burst spikes and burst tails by evaluating the cumulative moving average (CMA) and skewness of the ISI histogram. Because of the adaptive nature of the proposed algorithm, its analysis power is not limited by the type of neuronal cell network at hand. We demonstrate the functionality of our algorithm with two different types of microelectrode array (MEA) data recorded from spontaneously active hESC-derived neuronal cell networks. The same data was also analyzed by two commonly employed burst detection algorithms and the differences in burst detection results are illustrated. The results demonstrate that our method is both adaptive to the firing statistics of the network and yields successful burst detection from the data. In conclusion, the proposed method is a potential tool for analyzing of hESC-derived neuronal cell networks and thus can be utilized in studies aiming to understand the development and functioning of human neuronal networks and as an analysis tool for in vitro drug screening and neurotoxicity assays.

  4. The Venus Flytrap Dionaea muscipula Counts Prey-Induced Action Potentials to Induce Sodium Uptake.

    Science.gov (United States)

    Böhm, Jennifer; Scherzer, Sönke; Krol, Elzbieta; Kreuzer, Ines; von Meyer, Katharina; Lorey, Christian; Mueller, Thomas D; Shabala, Lana; Monte, Isabel; Solano, Roberto; Al-Rasheid, Khaled A S; Rennenberg, Heinz; Shabala, Sergey; Neher, Erwin; Hedrich, Rainer

    2016-02-08

    Carnivorous plants, such as the Venus flytrap (Dionaea muscipula), depend on an animal diet when grown in nutrient-poor soils. When an insect visits the trap and tilts the mechanosensors on the inner surface, action potentials (APs) are fired. After a moving object elicits two APs, the trap snaps shut, encaging the victim. Panicking preys repeatedly touch the trigger hairs over the subsequent hours, leading to a hermetically closed trap, which via the gland-based endocrine system is flooded by a prey-decomposing acidic enzyme cocktail. Here, we asked the question as to how many times trigger hairs have to be stimulated (e.g., now many APs are required) for the flytrap to recognize an encaged object as potential food, thus making it worthwhile activating the glands. By applying a series of trigger-hair stimulations, we found that the touch hormone jasmonic acid (JA) signaling pathway is activated after the second stimulus, while more than three APs are required to trigger an expression of genes encoding prey-degrading hydrolases, and that this expression is proportional to the number of mechanical stimulations. A decomposing animal contains a sodium load, and we have found that these sodium ions enter the capture organ via glands. We identified a flytrap sodium channel DmHKT1 as responsible for this sodium acquisition, with the number of transcripts expressed being dependent on the number of mechano-electric stimulations. Hence, the number of APs a victim triggers while trying to break out of the trap identifies the moving prey as a struggling Na(+)-rich animal and nutrition for the plant. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Anti-addiction Drug Ibogaine Prolongs the Action Potential in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

    Science.gov (United States)

    Rubi, Lena; Eckert, Daniel; Boehm, Stefan; Hilber, Karlheinz; Koenig, Xaver

    2017-04-01

    Ibogaine is a plant alkaloid used as anti-addiction drug in dozens of alternative medicine clinics worldwide. Recently, alarming reports of life-threatening cardiac arrhythmias and cases of sudden death associated with the ingestion of ibogaine have accumulated. Using whole-cell patch clamp recordings, we assessed the effects of ibogaine and its main metabolite noribogaine on action potentials in human ventricular-like cardiomyocytes derived from induced pluripotent stem cells. Therapeutic concentrations of ibogaine and its long-lived active metabolite noribogaine significantly retarded action potential repolarization in human cardiomyocytes. These findings represent the first experimental proof that ibogaine application entails a cardiac arrhythmia risk for humans. In addition, they explain the clinically observed delayed incidence of cardiac adverse events several days after ibogaine intake. We conclude that therapeutic concentrations of ibogaine retard action potential repolarization in the human heart. This may give rise to a prolongation of the QT interval in the electrocardiogram and cardiac arrhythmias.

  6. Patch-Clamp Recording from Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes: Improving Action Potential Characteristics through Dynamic Clamp.

    Science.gov (United States)

    Verkerk, Arie O; Veerman, Christiaan C; Zegers, Jan G; Mengarelli, Isabella; Bezzina, Connie R; Wilders, Ronald

    2017-08-30

    Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold great promise for studying inherited cardiac arrhythmias and developing drug therapies to treat such arrhythmias. Unfortunately, until now, action potential (AP) measurements in hiPSC-CMs have been hampered by the virtual absence of the inward rectifier potassium current (IK1) in hiPSC-CMs, resulting in spontaneous activity and altered function of various depolarising and repolarising membrane currents. We assessed whether AP measurements in "ventricular-like" and "atrial-like" hiPSC-CMs could be improved through a simple, highly reproducible dynamic clamp approach to provide these cells with a substantial IK1 (computed in real time according to the actual membrane potential and injected through the patch-clamp pipette). APs were measured at 1 Hz using perforated patch-clamp methodology, both in control cells and in cells treated with all-trans retinoic acid (RA) during the differentiation process to increase the number of cells with atrial-like APs. RA-treated hiPSC-CMs displayed shorter APs than control hiPSC-CMs and this phenotype became more prominent upon addition of synthetic IK1 through dynamic clamp. Furthermore, the variability of several AP parameters decreased upon IK1 injection. Computer simulations with models of ventricular-like and atrial-like hiPSC-CMs demonstrated the importance of selecting an appropriate synthetic IK1. In conclusion, the dynamic clamp-based approach of IK1 injection has broad applicability for detailed AP measurements in hiPSC-CMs.

  7. Patch-Clamp Recording from Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes: Improving Action Potential Characteristics through Dynamic Clamp

    Science.gov (United States)

    Veerman, Christiaan C.; Zegers, Jan G.; Mengarelli, Isabella; Bezzina, Connie R.

    2017-01-01

    Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold great promise for studying inherited cardiac arrhythmias and developing drug therapies to treat such arrhythmias. Unfortunately, until now, action potential (AP) measurements in hiPSC-CMs have been hampered by the virtual absence of the inward rectifier potassium current (IK1) in hiPSC-CMs, resulting in spontaneous activity and altered function of various depolarising and repolarising membrane currents. We assessed whether AP measurements in “ventricular-like” and “atrial-like” hiPSC-CMs could be improved through a simple, highly reproducible dynamic clamp approach to provide these cells with a substantial IK1 (computed in real time according to the actual membrane potential and injected through the patch-clamp pipette). APs were measured at 1 Hz using perforated patch-clamp methodology, both in control cells and in cells treated with all-trans retinoic acid (RA) during the differentiation process to increase the number of cells with atrial-like APs. RA-treated hiPSC-CMs displayed shorter APs than control hiPSC-CMs and this phenotype became more prominent upon addition of synthetic IK1 through dynamic clamp. Furthermore, the variability of several AP parameters decreased upon IK1 injection. Computer simulations with models of ventricular-like and atrial-like hiPSC-CMs demonstrated the importance of selecting an appropriate synthetic IK1. In conclusion, the dynamic clamp-based approach of IK1 injection has broad applicability for detailed AP measurements in hiPSC-CMs. PMID:28867785

  8. Toxicity, sublethal effects, and potential modes of action of select fungicides on freshwater fish and invertebrates

    Science.gov (United States)

    Elskus, Adria A.

    2012-01-01

    Despite decades of agricultural and urban use of fungicides and widespread detection of these pesticides in surface waters, relatively few data are available on the effects of fungicides on fish and invertebrates in the aquatic environment. Nine fungicides are reviewed in this report: azoxystrobin, boscalid, chlorothalonil, fludioxonil, myclobutanil, fenarimol, pyraclostrobin, pyrimethanil, and zoxamide. These fungicides were identified as emerging chemicals of concern because of their high or increasing global use rates, detection frequency in surface waters, or likely persistence in the environment. A review of the literature revealed significant sublethal effects of fungicides on fish, aquatic invertebrates, and ecosystems, including zooplankton and fish reproduction, fish immune function, zooplankton community composition, metabolic enzymes, and ecosystem processes, such as leaf decomposition in streams, among other biological effects. Some of these effects can occur at fungicide concentrations well below single-species acute lethality values (48- or 96-hour concentration that effects a response in 50 percent of the organisms, that is, effective concentration killing 50 percent of the organisms in 48 or 96 hours) and chronic sublethal values (for example, 21-day no observed adverse effects concentration), indicating that single-species toxicity values may dramatically underestimate the toxic potency of some fungicides. Fungicide modes of toxic action in fungi can sometimes reflect the biochemical and (or) physiological effects of fungicides observed in vertebrates and invertebrates; however, far more studies are needed to explore the potential to predict effects in nontarget organisms based on specific fungicide modes of toxic action. Fungicides can also have additive and (or) synergistic effects when used with other fungicides and insecticides, highlighting the need to study pesticide mixtures that occur in surface waters. For fungicides that partition to

  9. Action potential influences spatial perception: Evidence for genuine top-down effects on perception.

    Science.gov (United States)

    Witt, Jessica K

    2017-08-01

    The action-specific account of spatial perception asserts that a perceiver's ability to perform an action, such as hitting a softball or walking up a hill, impacts the visual perception of the target object. Although much evidence is consistent with this claim, the evidence has been challenged as to whether perception is truly impacted, as opposed to the responses themselves. These challenges have recently been organized as six pitfalls that provide a framework with which to evaluate the empirical evidence. Four case studies of action-specific effects are offered as evidence that meets the framework's high bar, and thus that demonstrates genuine perceptual effects. That action influences spatial perception is evidence that perceptual and action-related processes are intricately and bidirectionally linked.

  10. Red blood cell distribution width: a potential laboratory parameter for monitoring inflammation in rheumatoid arthritis.

    Science.gov (United States)

    He, Yujue; Liu, Can; Zeng, Zhiyong; Ye, Weilin; Lin, Jinpiao; Ou, Qishui

    2017-11-03

    Correlation analysis of red blood cell distribution width (RDW) and C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), tumor necrosis factor α (TNF-α), interleukin (IL)-6, and IL-10 in rheumatoid arthritis (RA) to investigate whether RDW can serve as a potential parameter for indicating inflammation in RA patients. A total of 670 RA patients from October 2014 to April 2016 were enrolled in our study. The white blood cell (WBC), red blood cell (RBC), platelet (PLT), hemoglobin (HGB), RDW, CRP, and ESR in peripheral blood of patients with RA were retrospectively analyzed. The relative expression of TNF-α, IL-6, and IL-10 was detected by RT-qPCR. Correlation analysis between RDW and CRP, ESR, TNF-α, IL-6, and IL-10 in RA was conducted by Microsoft Excel. RDW level was significantly increased in RA patients compared to osteoarthritis (OA) patients (P < 0.001) and healthy donors (HDs) (P < 0.001), and RDW was positively associated with inflammatory markers, such as CRP and ESR. In ROC curve analysis, the area under the curve (AUC) of RDW for the identification of RA was 0.881, with a 95% confidence interval (CI) from 0.864 to 0.898. Moreover, correlation analysis showed that RDW level was positively associated with TNF-α and IL-6, however negatively associated with IL-10. RDW was increased in patients with RA which was associated with inflammation in RA, suggesting that RDW may be a potential auxiliary marker for indicating inflammation process in RA conveniently.

  11. Amphetamine elevates nucleus accumbens dopamine via an action potential-dependent mechanism that is modulated by endocannabinoids.

    Science.gov (United States)

    Covey, Dan P; Bunner, Kendra D; Schuweiler, Douglas R; Cheer, Joseph F; Garris, Paul A

    2016-06-01

    The reinforcing effects of abused drugs are mediated by their ability to elevate nucleus accumbens dopamine. Amphetamine (AMPH) was historically thought to increase dopamine by an action potential-independent, non-exocytotic type of release called efflux, involving reversal of dopamine transporter function and driven by vesicular dopamine depletion. Growing evidence suggests that AMPH also acts by an action potential-dependent mechanism. Indeed, fast-scan cyclic voltammetry demonstrates that AMPH activates dopamine transients, reward-related phasic signals generated by burst firing of dopamine neurons and dependent on intact vesicular dopamine. Not established for AMPH but indicating a shared mechanism, endocannabinoids facilitate this activation of dopamine transients by broad classes of abused drugs. Here, using fast-scan cyclic voltammetry coupled to pharmacological manipulations in awake rats, we investigated the action potential and endocannabinoid dependence of AMPH-induced elevations in nucleus accumbens dopamine. AMPH increased the frequency, amplitude and duration of transients, which were observed riding on top of slower dopamine increases. Surprisingly, silencing dopamine neuron firing abolished all AMPH-induced dopamine elevations, identifying an action potential-dependent origin. Blocking cannabinoid type 1 receptors prevented AMPH from increasing transient frequency, similar to reported effects on other abused drugs, but not from increasing transient duration and inhibiting dopamine uptake. Thus, AMPH elevates nucleus accumbens dopamine by eliciting transients via cannabinoid type 1 receptors and promoting the summation of temporally coincident transients, made more numerous, larger and wider by AMPH. Collectively, these findings are inconsistent with AMPH eliciting action potential-independent dopamine efflux and vesicular dopamine depletion, and support endocannabinoids facilitating phasic dopamine signalling as a common action in drug reinforcement

  12. Potential of an outranking multi-criteria approach to support the participatory assessment of land management actions.

    Science.gov (United States)

    Ocampo-Melgar, Anahí; Bautista, Susana; Edward deSteiguer, J; Orr, Barron J

    2017-06-15

    We evaluated the potential of an outranking Multi-Criteria Decision Analysis approach for assisting in the participatory assessment of dryland management actions implemented in the San Simon watershed, in southeastern Arizona, USA. We compared an outranking-facilitated assessment of actions with a simple and direct (baseline) ranking of the same actions by the participating stakeholders in terms of: 1) internal homogeneity of each assessment approach, (2) similarity of individual assessments between methods, and (3) effects of the use of implicit/explicit assessment criteria. The actions assessed combined various management approaches, including livestock management (rotation, resting), vegetation management (grass seeding, brush control), and hydraulic structures (dams, dykes). The outranking-facilitated assessment discriminated better between actions and reduced the variability of results between individual stakeholders as compared with the direct ranking of actions. In general, the two assessments significantly differed in the relative preference of the five management actions assessed, yet both assessments identified rotational grazing combined with vegetation management (grass seeding and brush control) as the most preferred management action in the study area. The comparative analysis revealed inconsistencies between the use of implicit and explicit assessment criteria. Our findings highlight the opportunities offered by outranking approaches to help capture, structure, and make explicit stakeholder perspectives in the framework of a participatory environmental assessment process, which may facilitate the understanding of the multiple preferences involved. The outranking integration process, which resembles a voting procedure, proved simple and transparent, with potential for contributing to stakeholder engagement and trust in participatory assessment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Auditory nerve frequency tuning measured with forward-masked compound action potentials.

    Science.gov (United States)

    Verschooten, Eric; Robles, Luis; Kovačić, Damir; Joris, Philip X

    2012-12-01

    Frequency selectivity is a fundamental cochlear property. Recent studies using otoacoustic emissions and psychophysical forward masking suggest that frequency selectivity is sharper in human than in common laboratory species. This has been disputed based on reports using compound action potentials (CAPs), which reflect activity in the auditory nerve and can be measured in humans. Comparative data of CAPs, obtained with a variety of simultaneous masking protocols, have been interpreted to indicate similarity of frequency tuning across mammals and even birds. Unfortunately, there are several issues with the available CAP measurements which hamper a straightforward comparison across species. We investigate sharpness of CAP tuning in cat and chinchilla using a forward masking notched-noise paradigm--which is less confounded by cochlear nonlinearities than simultaneous masking paradigms and similar to what was used in the psychophysical study reporting sharper tuning in humans. Our parametric study, using different probe frequencies and notch widths, shows relationships consistent with those of auditory nerve fibers (ANFs). The sharpness of tuning, quantified by Q(10) factors, is negatively correlated with probe level and increases with probe frequency, but the Q(10) values are generally lower than the average trend for ANFs. Like the single fiber data, tuning for CAPs is sharper in cat than in chinchilla, but the two species are similar in the dependence of tuning on probe frequency and in the relationship between tuning in ANFs and CAP. Growth-of-maskability functions show slopes <1 indicating that with increasing probe level the probe is more susceptible to cochlear compression than the masker. The results support the use of forward-masked CAPs as an alternative measure to estimate ANF tuning and to compare frequency tuning across species.

  14. Dorsal Sural Sensory Nerve Action Potential: A Study for Reference Values.

    Science.gov (United States)

    Chaudhari, Sweta Chetan; Mansukhani, Khushnuma Anil; Sharma, Alika; Balakrishnan, Lajita; Sreenivasan, Aarthika

    2017-01-01

    Dorsal sural sensory nerve action potential (SNAP) could help diagnose early or subclinical peripheral neuropathy. To establish reference data for dorsal sural SNAP amplitude, latency, and velocity in healthy participants. A prospective study was conducted in 45 nerves from healthy participants between 18 and 90 years and stratified into three age groups (a = 18-40 years, b = 41-60 years, and c>60 years). StataCorp 12.2 statistical program was used for all statistical analyses. Mean-2 standard deviation was used to generate reference values for the lower limit of amplitude and velocity in each age group. ANOVA with Bonferroni correction was used for intergroup comparisons of amplitude and velocity. Regression analysis was used to compute an equation for the predicted amplitude with age, height, and weight as the covariates. The lower limit for amplitude (uv) in Groups a, b, and c was 2.57, 1.97, and 1.01, respectively. The lower limit for velocity (m/s) was 33.6, 32, and 22.8, respectively. Statistical significance was noted between the amplitudes of participants in Groups b and c ( P = 0.039) and a and c ( P = 0.001). Similarly, velocity was significantly different between Groups b and c ( P = 0.04) and a and c ( P = 0.008). Age was the covariate with maximum effect on the dorsal sural amplitude. Gender and side-to-side comparison did not show statistical significance for amplitude and velocity measurements. Linear regression analysis of the transformed amplitude gave the predictive equation as (y) =3.338 + age (-0.0167) + height in meters (-0.209) + weight (0.001). This study provides reference data for dorsal sural SNAP in Indian population stratified by age.

  15. Disruption of action potential and calcium signaling properties in malformed myofibers from dystrophin-deficient mice

    Science.gov (United States)

    Hernández-Ochoa, Erick O; Pratt, Stephen J P; Garcia-Pelagio, Karla P; Schneider, Martin F; Lovering, Richard M

    2015-01-01

    Duchenne muscular dystrophy (DMD), the most common and severe muscular dystrophy, is caused by the absence of dystrophin. Muscle weakness and fragility (i.e., increased susceptibility to damage) are presumably due to structural instability of the myofiber cytoskeleton, but recent studies suggest that the increased presence of malformed/branched myofibers in dystrophic muscle may also play a role. We have previously studied myofiber morphology in healthy wild-type (WT) and dystrophic (MDX) skeletal muscle. Here, we examined myofiber excitability using high-speed confocal microscopy and the voltage-sensitive indicator di-8-butyl-amino-naphthyl-ethylene-pyridinium-propyl-sulfonate (di-8-ANEPPS) to assess the action potential (AP) properties. We also examined AP-induced Ca2+ transients using high-speed confocal microscopy with rhod-2, and assessed sarcolemma fragility using elastimetry. AP recordings showed an increased width and time to peak in malformed MDX myofibers compared to normal myofibers from both WT and MDX, but no significant change in AP amplitude. Malformed MDX myofibers also exhibited reduced AP-induced Ca2+ transients, with a further Ca2+ transient reduction in the branches of malformed MDX myofibers. Mechanical studies indicated an increased sarcolemma deformability and instability in malformed MDX myofibers. The data suggest that malformed myofibers are functionally different from myofibers with normal morphology. The differences seen in AP properties and Ca2+ signals suggest changes in excitability and remodeling of the global Ca2+ signal, both of which could underlie reported weakness in dystrophic muscle. The biomechanical changes in the sarcolemma support the notion that malformed myofibers are more susceptible to damage. The high prevalence of malformed myofibers in dystrophic muscle may contribute to the progressive strength loss and fragility seen in dystrophic muscles. PMID:25907787

  16. Different calcium sources control somatic versus dendritic SK channel activation during action potentials.

    Science.gov (United States)

    Jones, Scott L; Stuart, Greg J

    2013-12-11

    Small-conductance calcium-activated potassium (SK) channels play an important role in regulating neuronal excitability. While SK channels at the soma have long been known to contribute to the medium afterhyperpolarization (mAHP), recent evidence indicates they also regulate NMDA receptor activation in dendritic spines. Here we investigate the activation of SK channels in spines and dendrites of rat cortical pyramidal neurons during action potentials (APs), and compare this to SK channel activation at the soma. Using confocal calcium imaging, we demonstrate that the inhibition of SK channels with apamin results in a location-dependent increase in calcium influx into dendrites and spines during backpropagating APs (average increase, ~40%). This effect was occluded by block of R-type voltage-dependent calcium channels (VDCCs), but not by inhibition of N- or P/Q-type VDCCs, or block of calcium release from intracellular stores. During these experiments, we noticed that the calcium indicator (Oregon Green BAPTA-1) blocked the mAHP. Subsequent experiments using low concentrations of EGTA (1 mm) produced the same result, suggesting that somatic SK channels are not tightly colocalized with their calcium source. Consistent with this idea, all known subtypes of VDCCs except R-type were calcium sources for the apamin-sensitive mAHP at the soma. We conclude that SK channels in spines and dendrites of cortical pyramidal neurons regulate calcium influx during backpropagating APs in a distance-dependent manner, and are tightly coupled to R-type VDCCs. In contrast, SK channels activated by APs at the soma of these neurons are weakly coupled to a variety of VDCCs.

  17. Effect of knockout of α2δ-1 on action potentials in mouse sensory neurons.

    Science.gov (United States)

    Margas, Wojciech; Ferron, Laurent; Nieto-Rostro, Manuela; Schwartz, Arnold; Dolphin, Annette C

    2016-08-05

    Gene deletion of the voltage-gated calcium channel auxiliary subunit α2δ-1 has been shown previously to have a cardiovascular phenotype, and a reduction in mechano- and cold sensitivity, coupled with delayed development of neuropathic allodynia. We have also previously shown that dorsal root ganglion (DRG) neuron calcium channel currents were significantly reduced in α2δ-1 knockout mice. To extend our findings in these sensory neurons, we have examined here the properties of action potentials (APs) in DRG neurons from α2δ-1 knockout mice in comparison to their wild-type (WT) littermates, in order to dissect how the calcium channels that are affected by α2δ-1 knockout are involved in setting the duration of individual APs and their firing frequency. Our main findings are that there is reduced Ca(2+) entry on single AP stimulation, particularly in the axon proximal segment, reduced AP duration and reduced firing frequency to a 400 ms stimulation in α2δ-1 knockout neurons, consistent with the expected role of voltage-gated calcium channels in these events. Furthermore, lower intracellular Ca(2+) buffering also resulted in reduced AP duration, and a lower frequency of AP firing in WT neurons, mimicking the effect of α2δ-1 knockout. By contrast, we did not obtain any consistent evidence for the involvement of Ca(2+)-activation of large conductance calcium-activated potassium (BK) and small conductance calcium-activated potassium (SK) channels in these events. In conclusion, the reduced Ca(2+) elevation as a result of single AP stimulation is likely to result from the reduced duration of the AP in α2δ-1 knockout sensory neurons.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. © 2016 The Authors.

  18. Suprathreshold compound action potential amplitude as a measure of auditory function in cochlear implant users

    Directory of Open Access Journals (Sweden)

    Rachel A. Scheperle

    2017-03-01

    Full Text Available Electrically evoked compound action potential (eCAP amplitudes elicited at suprathreshold levels were assessed as a measure of the effectiveness of cochlear implant (CI stimulation. Twenty-one individuals participated; one was excluded due to facial stimulation during eCAP testing. For each participant, eCAPs were elicited with stimulation from seven electrodes near the upper limit of the individual's electrical dynamic range. A reduced-channel CI program was created using those same seven electrodes, and participants performed a vowel discrimination task. Consistent with previous reports, eCAP amplitudes varied across tested electrodes; the profiles were unique to each individual. In 6 subjects (30%, eCAP amplitude variability was partially explained by the impedance of the recording electrode. The remaining amplitude variability within subjects, and the variability observed across subjects could not be explained by recording electrode impedance. This implies that other underlying factors, such as variations in neural status across the array, are responsible. Across-site mean eCAP amplitude was significantly correlated with vowel discrimination scores (r2 = 0.56. A single eCAP amplitude measured from the middle of the array was also significantly correlated with vowel discrimination, but the correlation was weaker (r2 = 0.37, though not statistically different from the across-site mean. Normalizing each eCAP amplitude by its associated recording electrode impedance did not improve the correlation with vowel discrimination (r2 = 0.52. Further work is needed to assess whether combining eCAP amplitude with other measures of the electrode-neural interface and/or with more central measures of auditory function provides a more complete picture of auditory function in CI recipients.

  19. Electrically evoked compound action potentials artefact rejection by independent component analysis: procedure automation.

    Science.gov (United States)

    Akhoun, Idrick; McKay, Colette; El-Deredy, Wael

    2015-01-15

    Independent-components-analysis (ICA) successfully separated electrically-evoked compound action potentials (ECAPs) from the stimulation artefact and noise (ECAP-ICA, Akhoun et al., 2013). This paper shows how to automate the ECAP-ICA artefact cancellation process. Raw-ECAPs without artefact rejection were consecutively recorded for each stimulation condition from at least 8 intra-cochlear electrodes. Firstly, amplifier-saturated recordings were discarded, and the data from different stimulus conditions (different current-levels) were concatenated temporally. The key aspect of the automation procedure was the sequential deductive source categorisation after ICA was applied with a restriction to 4 sources. The stereotypical aspect of the 4 sources enables their automatic classification as two artefact components, a noise and the sought ECAP based on theoretical and empirical considerations. The automatic procedure was tested using 8 cochlear implant (CI) users and one to four stimulus electrodes. The artefact and noise sources were successively identified and discarded, leaving the ECAP as the remaining source. The automated ECAP-ICA procedure successfully extracted the correct ECAPs compared to standard clinical forward masking paradigm in 22 out of 26 cases. ECAP-ICA does not require extracting the ECAP from a combination of distinct buffers as it is the case with regular methods. It is an alternative that does not have the possible bias of traditional artefact rejections such as alternate-polarity or forward-masking paradigms. The ECAP-ICA procedure bears clinical relevance, for example as the artefact rejection sub-module of automated ECAP-threshold detection techniques, which are common features of CI clinical fitting software. Copyright © 2014. Published by Elsevier B.V.

  20. Resurgent sodium current promotes action potential firing in the avian auditory brainstem.

    Science.gov (United States)

    Hong, Hui; Lu, Ting; Wang, Xiaoyu; Wang, Yuan; Sanchez, Jason Tait

    2017-11-28

    Auditory brainstem neurons are functionally primed to fire action potentials (APs) at markedly high-rates in order to rapidly encode acoustic information of sound. This specialization is critical for survival and the comprehension of behaviourally relevant communication functions, including sound localization and understanding speech in noise. Here, we investigated underlying ion channel mechanisms essential for high-rate AP firing in neurons of the chicken nucleus magnocellularis (NM) - the avian analog of bushy cells of the mammalian anteroventral cochlear nucleus. In addition to the established function of high-voltage activated potassium channels, we found that resurgent sodium current (INaR ) plays a role in regulating rapid firing activity of late-developing (embryonic [E] days 19-21) NM neurons. INaR of late-developing NM neurons showed similar properties with mammalian neurons in that its unique mechanism of an "open channel block state" facilitated the recovery and increased the availability of sodium (NaV ) channels after depolarization. Using a computational model of NM neurons, we demonstrated that removal of INaR reduced high-rate AP firing. We found weak INaR during a prehearing period (E11-12), which transformed to resemble late-developing INaR properties around hearing onset (E14-16). Anatomically, we detected strong NaV 1.6 expression near maturation, which became increasingly less distinct at hearing onset and prehearing periods, suggesting that multiple NaV channel subtypes may contribute to INaR during development. We conclude that INaR plays an important role in regulating rapid AP firing for NM neurons, a property that may be evolutionarily conserved for functions related to similar avian and mammalian hearing. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  1. Mechanisms of lidocaine's action on subtypes of spinal dorsal horn neurons subject to the diverse roles of Na(+) and K(+) channels in action potential generation.

    Science.gov (United States)

    Wolff, Matthias; Schnöbel-Ehehalt, Rose; Mühling, Jörg; Weigand, Markus A; Olschewski, Andrea

    2014-08-01

    Superficial dorsal horn neurons of the spinal cord receive sensory information from Aδ and C fibers. According to their response to sustained depolarization, these cells can be divided into 3 groups: tonic (TFN), adapting (AFN), and single spike firing (SSN) neurons. During spinal and systemic administration of lidocaine, these neurons are exposed to different concentrations of the local anesthetic lidocaine. In this study, we explored its effect on the excitability of sensory neurons. Whole-cell patch-clamp recordings from dorsal horn neurons of Wistar rats were used to study the action of lidocaine on firing properties. To estimate the impact of a blockade of voltage-gated potassium channels by lidocaine (100 μM) on the firing properties of different neurons, the sodium and potassium channel inhibition of lidocaine was investigated in the light of the effects of tetrodotoxin (TTX, 10 nM) and tetraethylammonium (10 mM). For statistical analysis, the Wilcoxon matched-pairs signed rank test was used throughout. All 3 types of neurons responded to lidocaine with changes in the shape of their action potentials. The peak amplitude of the single action potentials was decreased (P = 0.031, P = 0.013, and P = 0.014 for SSN, AFN, and TFN neurons, respectively), and the duration of the action potentials was increased (P = 0.016, P = 0.032, and P = 0.031 for SSN, AFN, and TFN neurons, respectively). The maximum positive slope (P = 0.016 and P = 0.0010 for SSN and AFN, respectively) and the negative slope (P = 0.016, P = 0.0025, and P = 0.020 for SSN, AFN, and TFN neurons, respectively) decreased after application of lidocaine. In tonically firing neurons, lidocaine reduced the repetitive firing (P = 0.0016), and this effect was mimicked by a combination of TTX and tetraethylammonium. In AFN, TTX mimicked the action of lidocaine. Lidocaine at low concentrations suppresses tonic firing neurons by interacting with voltage-gated potassium channels. The effects on adapting

  2. Calcium-Activated Chloride Channels (CaCCs) Regulate Action Potential and Synaptic Response in Hippocampal Neurons

    Science.gov (United States)

    Huang, Wendy C.; Xiao, Shaohua; Huang, Fen; Harfe, Brian D.; Jan, Yuh Nung; Jan, Lily Yeh

    2012-01-01

    SUMMARY Central neurons respond to synaptic inputs from other neurons by generating synaptic potentials. Once the summated synaptic potentials reach threshold for action potential firing, the signal propagates leading to transmitter release at the synapse. The calcium influx accompanying such signaling opens calcium-activated ion channels for feedback regulation. Here we report a novel mechanism for modulating hippocampal neuronal signaling that involves calcium-activated chloride channels (CaCCs). We present the first evidence that CaCCs reside in hippocampal neurons and are in close proximity of calcium channels and NMDA receptors to shorten action potential duration, dampen excitatory synaptic potentials, impede temporal summation, and raise the threshold for action potential generation by synaptic potential. Having recently identified TMEM16A and TMEM16B as CaCCs, we further show that TMEM16B but not TMEM16A is important for hippocampal CaCC, laying the groundwork for deciphering the dynamic CaCC modulation of neuronal signaling in neurons important for learning and memory. PMID:22500639

  3. An exploratory investigation of various modes of action and potential adverse outcomes of fluoxetine in marine mussels

    Energy Technology Data Exchange (ETDEWEB)

    Franzellitti, Silvia, E-mail: silvia.franzellitti@unibo.it [University of Bologna, Interdepartment Centre for Environmental Science Research, via S. Alberto 163, 48123 Ravenna (Italy); University of Bologna, Department of Biological, Geological, and Environmental Sciences, via Selmi 3, 40100 Bologna (Italy); Buratti, Sara; Capolupo, Marco [University of Bologna, Interdepartment Centre for Environmental Science Research, via S. Alberto 163, 48123 Ravenna (Italy); Du, Bowen; Haddad, Samuel P. [Department of Environmental Science, Baylor University, Waco, TX 76798 (United States); Chambliss, C. Kevin [Department of Chemistry and Biochemistry, Baylor University, Waco, TX 76798 (United States); Brooks, Bryan W. [Department of Environmental Science, Baylor University, Waco, TX 76798 (United States); Fabbri, Elena [University of Bologna, Interdepartment Centre for Environmental Science Research, via S. Alberto 163, 48123 Ravenna (Italy); University of Bologna, Department of Biological, Geological, and Environmental Sciences, via Selmi 3, 40100 Bologna (Italy)

    2014-06-01

    Highlights: • Mode of action (MOA) related endpoints and biomarkers of toxicity were assessed in mussels exposed to fluoxetine (FX). • Significant FX bioaccumulation was observed in tissues of mussels exposed to 30 and 300 ng/L FX. • Alterations of cAMP-related cell signaling were observed in exposed mussels as part of the MOA of FX. • FX reduced the health status of mussels inducing lysosomal effects in digestive gland and antioxidant responses in gills. • The importance of considering additional MOAs and adverse outcome pathways for FX impacts on mussels is highlighted. - Abstract: The present study investigated possible adverse outcome pathways (AOPs) of the antidepressant fluoxetine (FX) in the marine mussel Mytilus galloprovincialis. An evaluation of molecular endpoints involved in modes of action (MOAs) of FX and biomarkers for sub-lethal toxicity were explored in mussels after a 7-day administration of nominal FX concentrations encompassing a range of environmentally relevant values (0.03–300 ng/L). FX bioaccumulated in mussel tissues after treatment with 30 and 300 ng/L FX, resulting in bioconcentration factor (BCF) values ranging from 200 to 800, which were higher than expected based solely on hydrophobic partitioning models. Because FX acts as a selective serotonin (5-HT) re-uptake inhibitor increasing serotonergic neurotransmission at mammalian synapses, cell signaling alterations triggered by 5-HT receptor occupations were assessed. cAMP levels and PKA activities were decreased in digestive gland and mantle/gonads of FX-treated mussels, consistent with an increased occupation of 5-HT1 receptors negatively coupled to the cAMP/PKA pathway. mRNA levels of a ABCB gene encoding the P-glycoprotein were also significantly down-regulated. This membrane transporter acts in detoxification towards xenobiotics and in altering pharmacokinetics of antidepressants; moreover, it is under a cAMP/PKA transcriptional regulation in mussels. Potential stress

  4. Microscopic and macroscopic volume conduction in skeletal muscle tissue, applied to simulation of single-fibre action potentials

    NARCIS (Netherlands)

    Alberts, B.A.; Rutten, Wim; Wallinga, W.; Boom, H.B.K.

    1988-01-01

    Extracellular action potentials of a single active muscle fibre in a surrounding of passive muscle tissue were calculated, using a microscopic volume conductor model which accounts for the travelling aspect of the source, the structure of skeletal muscle tissue and the electrical properties at the

  5. Serotonin spillover onto the axon initial segment of motoneurons induces central fatigue by inhibiting action potential initiation

    DEFF Research Database (Denmark)

    Cotel, Florence; Exley, Richard; Cragg, Stephanie

    2013-01-01

    --as during motor exercise--activated 5-HT1A receptors that decreased motoneuronal excitability. Electrophysiological tests combined with pharmacology showed that focal activation of 5-HT1A receptors at the axon initial segment (AIS), but not on other motoneuronal compartments, inhibited the action potential...

  6. Analysis of electrically evoked compound action potential of the auditory nerve in children with bilateral cochlear implants.

    Science.gov (United States)

    Caldas, Fernanda Ferreira; Cardoso, Carolina Costa; Barreto, Monique Antunes de Souza Chelminski; Teixeira, Marina Santos; Hilgenberg, Anacléia Melo da Silva; Serra, Lucieny Silva Martins; Bahmad Junior, Fayez

    2016-01-01

    The cochlear implant device has the capacity to measure the electrically evoked compound action potential of the auditory nerve. The neural response telemetry is used in order to measure the electrically evoked compound action potential of the auditory nerve. To analyze the electrically evoked compound action potential, through the neural response telemetry, in children with bilateral cochlear implants. This is an analytical, prospective, longitudinal, historical cohort study. Six children, aged 1-4 years, with bilateral cochlear implant were assessed at five different intervals during their first year of cochlear implant use. There were significant differences in follow-up time (p=0.0082) and electrode position (p=0.0019) in the T-NRT measure. There was a significant difference in the interaction between time of follow-up and electrode position (p=0.0143) when measuring the N1-P1 wave amplitude between the three electrodes at each time of follow-up. The electrically evoked compound action potential measurement using neural response telemetry in children with bilateral cochlear implants during the first year of follow-up was effective in demonstrating the synchronized bilateral development of the peripheral auditory pathways in the studied population. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  7. The role of action potential alternans in the initiation of atrial fibrillation in humans: a review and future directions

    Science.gov (United States)

    Franz, Michael R.; Jamal, Sameer M.; Narayan, Sanjiv M.

    2012-01-01

    This review highlights the role of atrial monophasic action potential duration (APD) in understanding atrial electrical properties in paroxysmal, persistent, and permanent atrial fibrillation (AF) states. Alternans of APD and rate maladaptation in a spatially divergent way appear mechanistically involved in AF initiation, development, and persistence. The underlying pathophysiology warrants further investigation. PMID:23104916

  8. Channelrhodopsin-2-expressed dorsal root ganglion neurons activates calcium channel currents and increases action potential in spinal cord.

    Science.gov (United States)

    Zhang, Yi; Yue, Jing; Ai, Midan; Ji, Zhigang; Liu, Zhiguo; Cao, Xuehong; Li, Li

    2014-07-01

    We used optogenetic techniques in spinal cord and dorsal root ganglion (DRG) neuron studies. This study investigated changes in channelrhodopsin-2 (ChR2) expression in the spinal cord and DRG neurons using optogenetic techniques. The results show the possibility of using optogenetics to treat neuropathic pain. Previous studies have shown that activated ChR2 induces an increase in DRG neuron action potential. Western blot analysis was used to measure ChR2 protein levels in the spinal cord and DRG neurons or rats intrathecally injected with ChR2 lentivirus. Electrophysiology recording was used to detect differences in action potential levels in the spinal cord and calcium channel currents in the DRG neurons. Our studies showed that ChR2 expression increased the action potential in the spinal cord and increased calcium channel currents in DRG neurons. We successfully expressed the ChR2 protein in the spinal cord and DRG neurons. We also found that ChR2 increased the action potential in the spinal cord and activated the calcium channel in DRG neurons. These findings support the research possibilities of using optogenetic studies to improve treatment for neuropathic pain. N/A.

  9. Flattening of the electrocardiographic T-wave is a sign of proarrhythmic risk and a reflection of action potential triangulation

    DEFF Research Database (Denmark)

    Bhuiyan, Tanveer Ahmed; Graff, Claus; Kanters, J.K.

    2013-01-01

    Drug-induced triangulation of the cardiac action potential is associated with increased risk of arrhythmic events. It has been suggested that triangulation causes a flattening of the electrocardiographic T-wave but the relationship between triangulation, T-wave flattening and onset of arrhythmia...

  10. The influence of cochlear hearing loss and probe tone level on compound action potential tuning curves in humans

    NARCIS (Netherlands)

    Rutten, Wim

    1986-01-01

    The effect of cochlear hearing loss and of probe tone level on slopes and sharpness of compound action potential tuning curves was investigated. Thirty-one simultaneously masked isoreduction (50%) tuning curves were determined in 26 adults with cochlear hearing losses up to 60 dB. Probe tone

  11. Action potential generation in the small intestine of W mutant mice that lack interstitial cells of Cajal

    DEFF Research Database (Denmark)

    Malysz, J; Thuneberg, L; Mikkelsen, Hanne Birte

    1996-01-01

    + channel blockade evoked the typical spikelike action potentials. Electron microscopy identified few methylene blue-positive cells in the W/Wv small intestine associated with Auerbach's plexus as individual ICC. Numbers of resident macrophage-like cells (MLC) and fibroblast-like cells (FLC) were...

  12. Long-QT syndrome-related sodium channel mutations probed by the dynamic action potential clamp technique

    NARCIS (Netherlands)

    Berecki, Géza; Zegers, Jan G.; Bhuiyan, Zahurul A.; Verkerk, Arie O.; Wilders, Ronald; van Ginneken, Antoni C. G.

    2006-01-01

    Long-QT3 syndrome (LQT3) is linked to cardiac sodium channel gene (SCN5A) mutations. In this study, we used the 'dynamic action potential clamp' (dAPC) technique to effectively replace the native sodium current (I(Na)) of the Priebe-Beuckelmann human ventricular cell model with wild-type (WT) or

  13. Processing of thermal parameters for the assessment of geothermal potential of sedimentary basins

    Science.gov (United States)

    Pasquale, V.; Chiozzi, P.; Gola, G.; Verdoya, M.

    2009-04-01

    The growing interest on renewable energy sources is stimulating new efforts aimed at the assessment of geothermal potential in several countries, and new developments are expected in the near future. In this framework, a basic step forward is to focus geothermal investigations on geological environments which so far have been relatively neglected. Some intracontinental sedimentary basins could reveal important low enthalpy resources. The evaluation of the geothermal potential in such geological contexts involves the synergic use of geophysical and hydrogeological methodologies. In sedimentary basins a large amount of thermal and hydraulic data is generally available from petroleum wells. Unfortunately, borehole temperature data are often affected by a number of perturbations which make very difficult determination of the true geothermal gradient. In this paper we addressed the importance of the acquisition of thermal parameters (temperature, geothermal gradient, thermal properties of the rock) and the technical processing which is necessary to obtain reliable geothermal characterizations. In particular, techniques for corrections of bottom-hole temperature (BHT) data were reviewed. The objective was to create a working formula usable for computing the undisturbed formation temperature for specific sedimentary basins. As test areas, we analysed the sedimentary basins of northern Italy. Two classical techniques for processing temperature data from oil wells are customarily used: (i) the method by Horner, that requires two or more measurements of bottom-hole temperatures carried out at the same depth but at different shut-in times te and (ii) the technique by Cooper and Jones, in which several physical parameters of the mud and formation need to be known. We applied both methods to data from a number of petroleum explorative wells located in two areas of the Po Plain (Apenninic buried arc and South Piedmont Basin - Pedealpine homocline). From a set of about 40 wells

  14. Hydrodynamic parameters estimation from self-potential data in a controlled full scale site

    Science.gov (United States)

    Chidichimo, Francesco; De Biase, Michele; Rizzo, Enzo; Masi, Salvatore; Straface, Salvatore

    2015-03-01

    A multi-physical approach developed for the hydrodynamic characterization of porous media using hydrogeophysical information is presented. Several pumping tests were performed in the Hydrogeosite Laboratory, a controlled full-scale site designed and constructed at the CNR-IMAA (Consiglio Nazionale delle Ricerche - Istituto di Metodologia per l'Analisi Ambientale), in Marsico Nuovo (Basilicata Region, Southern Italy), in order to obtain an intermediate stage between laboratory experiments and field survey. The facility consists of a pool, used to study water infiltration processes, to simulate the space and time dynamics of subsurface contamination phenomena, to improve and to find new relationship between geophysical and hydrogeological parameters, to test and to calibrate new geophysical techniques and instruments. Therefore, the Hydrogeosite Laboratory has the advantage of carrying out controlled experiments, like in a flow cell or sandbox, but at field comparable scale. The data collected during the experiments have been used to estimate the saturated hydraulic conductivity ks [ms-1] using a coupled inversion model working in transient conditions, made up of the modified Richards equation describing the water flow in a variably saturated porous medium and the Poisson equation providing the self-potential ϕ [V], which naturally occurs at points of the soil surface owing to the presence of an electric field produced by the motion of underground electrolytic fluids through porous systems. The result obtained by this multi-physical numerical approach, which removes all the approximations adopted in previous works, makes a useful instrument for real heterogeneous aquifer characterization and for predictive analysis of its behavior.

  15. Potential of polarization lidar to provide profiles of CCN- and INP-relevant aerosol parameters

    Directory of Open Access Journals (Sweden)

    R.-E. Mamouri

    2016-05-01

    Full Text Available We investigate the potential of polarization lidar to provide vertical profiles of aerosol parameters from which cloud condensation nucleus (CCN and ice nucleating particle (INP number concentrations can be estimated. We show that height profiles of particle number concentrations n50, dry considering dry aerosol particles with radius  > 50 nm (reservoir of CCN in the case of marine and continental non-desert aerosols, n100, dry (particles with dry radius  >  100 nm, reservoir of desert dust CCN, and of n250, dry (particles with dry radius  >  250 nm, reservoir of favorable INP, as well as profiles of the particle surface area concentration sdry (used in INP parameterizations can be retrieved from lidar-derived aerosol extinction coefficients σ with relative uncertainties of a factor of 1.5–2 in the case of n50, dry and n100, dry and of about 25–50 % in the case of n250, dry and sdry. Of key importance is the potential of polarization lidar to distinguish and separate the optical properties of desert aerosols from non-desert aerosol such as continental and marine particles. We investigate the relationship between σ, measured at ambient atmospheric conditions, and n50, dry for marine and continental aerosols, n100, dry for desert dust particles, and n250, dry and sdry for three aerosol types (desert, non-desert continental, marine and for the main lidar wavelengths of 355, 532, and 1064 nm. Our study is based on multiyear Aerosol Robotic Network (AERONET photometer observations of aerosol optical thickness and column-integrated particle size distribution at Leipzig, Germany, and Limassol, Cyprus, which cover all realistic aerosol mixtures. We further include AERONET data from field campaigns in Morocco, Cabo Verde, and Barbados, which provide pure dust and pure marine aerosol scenarios. By means of a simple CCN parameterization (with n50, dry or n100, dry as input and available INP

  16. Spectral sampling tools for vegetation biophysical parameters and flux measurements in Europe: the European ES0903 COST Action

    Science.gov (United States)

    Vescovo, L.

    2010-12-01

    The estimate of carbon sequestration by terrestrial ecosystems and the prediction of the global change impact on the ecosystem carbon balance are becoming urgent needs required by international agreements. To support the development of this knowledge, a deep insight into processes that regulate carbon exchanges between terrestrial ecosystems and the atmosphere is fundamental. Flux towers remain a primary tool for understanding ecosystem carbon fluxes within the global flux networks. International initiatives such as SpecNet are developing to fill the temporal and spatial gap between ecosystem measurements and remote sensing by means of scale-appropriate optical measurements. In this framework, a new EU COST Action project has started in Europe. Up to now, 16 countries are participating to the Action. The COST Action project is open to researchers from European Cost Countries, but also from Near-Neighbour and non-COST countries can participate to the Action and, in some cases, can obtain some specific national funding (e.g. Australia, New Zealand, South Africa, Argentina). According to the highlighted scientific questions, the objectives of ES0903 are i) to analyse the state of the art of the optical sampling research in Europe, ii) to standardize tools and methods in the optical sampling measurements, iii) to focus on the fluxes and biomass estimation problems as an input to the technological world for development of new sensors and iv) to involve the scientific instruments industries in designing and testing a common multi-band reflectance sensor for ground optical measurements in the European flux network. Thanks to the Action, the use of standardised protocols will be encouraged within a spectral measurements network, across site comparisons will be enabled and the use of new instruments and sensors will be promoted and tested. Some of the most common issues of the proximal sampling research, performed at ecosystem level, are: i)methods, protocols and

  17. S-parameter at Non-Zero Temperature and Chemical Potential

    DEFF Research Database (Denmark)

    Søndergaard, Ulrik Ishøj; Sannino, Francesco; Pica, Claudio

    2011-01-01

    We compute the finite-temperature and matter density corrections to the S-parameter at the one loop level. At non-zero temperature T and matter density Lorentz symmetry breaks and therefore we suggest a suitable generalization of the S-parameter. By computing the plasma correction, we discover a ...

  18. Revealing calcium fluxes by analyzing inhibition dynamics in action potential clamp.

    Science.gov (United States)

    Laasmaa, Martin; Birkedal, Rikke; Vendelin, Marko

    2016-11-01

    In cardiac excitation-contraction coupling (ECC), calcium enters the cytosol via L-type Ca 2+ channels (LTCC) and reverse Na + /Ca 2+ -exchange (NCX rev ), or is released from the sarcoplasmic reticulum (SR) by Ca 2+ -induced Ca 2+ -release (CICR). The magnitude of Ca 2+ influx via the different pathways varies with the state of the cell and is difficult to assess quantitatively, because changes in Ca 2+ influx through one pathway affect the others. In rainbow trout ventricular myocytes, the role of the SR has been uncertain for decades. The aim of this work was therefore two-fold: 1) to develop a method to quantify the Ca 2+ influx pathways, and 2) to determine the role of CICR from the SR in trout ventricular myocytes. The novelty of our developed method lies in the mathematical analysis of measured transsarcolemmal Ca 2+ currents and their impact on the corresponding Ca 2+ transient during gradual inhibition of the currents in action potential (AP) clamp. We tested the developed method using an excitation-contraction model and showed that the method was able to recover calcium fluxes from noisy synthetic data. We applied the approach to trout ventricular myocytes and quantified the relative contributions of different Ca 2+ influx pathways in ECC and determined the kinetics of these fluxes. Under baseline conditions, NCX rev is the main transmembrane Ca 2+ influx pathway contributing 29 ± 6% (of the Ca 2+ influx), LTCC 18 ± 7%, and CICR 53 ± 10% to overall Ca 2+ transient. Thus, NCX rev is an important regulator of contractility and probably plays a role in the negative force-frequency relationship of trout ventricular preparations. These results demonstrate that trout and neonatal mammalian cardiomyocytes resemble each other not only in terms of morphology and energetics but ECC as well. In summary, the developed method resolves the major problem how to separate highly interconnected fluxes in AP clamp and allows to study Ca 2+ fluxes in cardiomyocytes under

  19. Ventilation inhibits sympathetic action potential recruitment even during severe chemoreflex stress.

    Science.gov (United States)

    Badrov, Mark B; Barak, Otto F; Mijacika, Tanja; Shoemaker, Leena N; Borrell, Lindsay J; Lojpur, Mihajlo; Drvis, Ivan; Dujic, Zeljko; Shoemaker, J Kevin

    2017-11-01

    This study investigated the influence of ventilation on sympathetic action potential (AP) discharge patterns during varying levels of high chemoreflex stress. In seven trained breath-hold divers (age 33 ± 12 yr), we measured muscle sympathetic nerve activity (MSNA) at baseline, during preparatory rebreathing (RBR), and during 1 ) functional residual capacity apnea (FRC Apnea ) and 2 ) continued RBR. Data from RBR were analyzed at matched (i.e., to FRC Apnea ) hemoglobin saturation (HbSat) levels (RBR Matched ) or more severe levels (RBR End ). A third protocol compared alternating periods (30 s) of FRC and RBR (FRC-RBR ALT ). Subjects continued each protocol until 85% volitional tolerance. AP patterns in MSNA (i.e., providing the true neural content of each sympathetic burst) were studied using wavelet-based methodology. First, for similar levels of chemoreflex stress (both HbSat: 71 ± 6%; P = NS), RBR Matched was associated with reduced AP frequency and APs per burst compared with FRC Apnea (both P < 0.001). When APs were binned according to peak-to-peak amplitude (i.e., into clusters), total AP clusters increased during FRC Apnea (+10 ± 2; P < 0.001) but not during RBR Matched (+1 ± 2; P = NS). Second, despite more severe chemoreflex stress during RBR End (HbSat: 56 ± 13 vs. 71 ± 6%; P < 0.001), RBR End was associated with a restrained increase in the APs per burst (FRC Apnea : +18 ± 7; RBR End : +11 ± 5) and total AP clusters (FRC Apnea : +10 ± 2; RBR End : +6 ± 4) (both P < 0.01). During FRC-RBR ALT , all periods of FRC elicited sympathetic AP recruitment (all P < 0.001), whereas all periods of RBR were associated with complete withdrawal of AP recruitment (all P = NS). Presently, we demonstrate that ventilation per se restrains and/or inhibits sympathetic axonal recruitment during high, and even extreme, chemoreflex stress. NEW & NOTEWORTHY The current study demonstrates that the sympathetic neural recruitment

  20. Effects of selected pharmacological agents on avian auditory and vestibular compound action potentials.

    Science.gov (United States)

    Irons-Brown, Shunda R; Jones, Timothy A

    2004-09-01

    Glutamate is currently the consensus candidate for the hair cell transmitter in the inner ear of vertebrates. However, other candidate transmitter systems have been proposed and there may be differences in this regard for auditory and vestibular neuroepithelia. In the present study, perilymphatic perfusion was used to deliver prescribed concentrations of ten drugs to the interstitial fluids of the inner ear of hatchling chickens (n = 124). Dose-response curves were obtained for four of these pharmacological agents. The work was carried out in part to distinguish further the neuroepithelial chemical receptors mediating auditory and vestibular compound action potentials (CAPs). Kainic acid (KA) eliminated both auditory and vestibular responses. D-alpha-Aminoadipic acid (DAA) and dizocilpine maleate (MK-801), both NMDA-specific antagonists, failed to alter vestibular CAPs at any concentration. MK-801 significantly and selectively reduced auditory CAPs at concentrations equal to or greater than 1 mM. Similarly, kynurenic acid (4-hydroxyquinoline-2-carboxylic acid, 1 mM), a glutamate antagonist, significantly reduced auditory but not vestibular CAPs. A non-NMDA glutamate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), reduced vestibular CAPs significantly but only at the highest concentration tested (1 mM). In contrast, CNQX reduced auditory responses at concentration as low as 1 microM. The CNQX concentration effective in reducing auditory CAPs by 50% (EC(50)) was approximately 20 microM. Glutamate (1 mM) as well as alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), a glutamate agonist, significantly reduced auditory CAPs (AMPA EC(50)=100 microM). Bicuculline, a GABA(A) receptor antagonist, and L-NAME, a nitric oxide synthase inhibitor, failed to alter responses from either modality. These findings support the hypothesis that glutamate receptors mediate auditory CAPs in birds. However, the results underscore a remarkable difference in

  1. Simulation of the undiseased human cardiac ventricular action potential: model formulation and experimental validation.

    Directory of Open Access Journals (Sweden)

    Thomas O'Hara

    2011-05-01

    Full Text Available Cellular electrophysiology experiments, important for understanding cardiac arrhythmia mechanisms, are usually performed with channels expressed in non myocytes, or with non-human myocytes. Differences between cell types and species affect results. Thus, an accurate model for the undiseased human ventricular action potential (AP which reproduces a broad range of physiological behaviors is needed. Such a model requires extensive experimental data, but essential elements have been unavailable. Here, we develop a human ventricular AP model using new undiseased human ventricular data: Ca(2+ versus voltage dependent inactivation of L-type Ca(2+ current (I(CaL; kinetics for the transient outward, rapid delayed rectifier (I(Kr, Na(+/Ca(2+ exchange (I(NaCa, and inward rectifier currents; AP recordings at all physiological cycle lengths; and rate dependence and restitution of AP duration (APD with and without a variety of specific channel blockers. Simulated APs reproduced the experimental AP morphology, APD rate dependence, and restitution. Using undiseased human mRNA and protein data, models for different transmural cell types were developed. Experiments for rate dependence of Ca(2+ (including peak and decay and intracellular sodium ([Na(+](i in undiseased human myocytes were quantitatively reproduced by the model. Early afterdepolarizations were induced by I(Kr block during slow pacing, and AP and Ca(2+ alternans appeared at rates >200 bpm, as observed in the nonfailing human ventricle. Ca(2+/calmodulin-dependent protein kinase II (CaMK modulated rate dependence of Ca(2+ cycling. I(NaCa linked Ca(2+ alternation to AP alternans. CaMK suppression or SERCA upregulation eliminated alternans. Steady state APD rate dependence was caused primarily by changes in [Na(+](i, via its modulation of the electrogenic Na(+/K(+ ATPase current. At fast pacing rates, late Na(+ current and I(CaL were also contributors. APD shortening during restitution was primarily

  2. Simulation of the Undiseased Human Cardiac Ventricular Action Potential: Model Formulation and Experimental Validation

    Science.gov (United States)

    O'Hara, Thomas; Virág, László; Varró, András; Rudy, Yoram

    2011-01-01

    Cellular electrophysiology experiments, important for understanding cardiac arrhythmia mechanisms, are usually performed with channels expressed in non myocytes, or with non-human myocytes. Differences between cell types and species affect results. Thus, an accurate model for the undiseased human ventricular action potential (AP) which reproduces a broad range of physiological behaviors is needed. Such a model requires extensive experimental data, but essential elements have been unavailable. Here, we develop a human ventricular AP model using new undiseased human ventricular data: Ca2+ versus voltage dependent inactivation of L-type Ca2+ current (ICaL); kinetics for the transient outward, rapid delayed rectifier (IKr), Na+/Ca2+ exchange (INaCa), and inward rectifier currents; AP recordings at all physiological cycle lengths; and rate dependence and restitution of AP duration (APD) with and without a variety of specific channel blockers. Simulated APs reproduced the experimental AP morphology, APD rate dependence, and restitution. Using undiseased human mRNA and protein data, models for different transmural cell types were developed. Experiments for rate dependence of Ca2+ (including peak and decay) and intracellular sodium ([Na+]i) in undiseased human myocytes were quantitatively reproduced by the model. Early afterdepolarizations were induced by IKr block during slow pacing, and AP and Ca2+ alternans appeared at rates >200 bpm, as observed in the nonfailing human ventricle. Ca2+/calmodulin-dependent protein kinase II (CaMK) modulated rate dependence of Ca2+ cycling. INaCa linked Ca2+ alternation to AP alternans. CaMK suppression or SERCA upregulation eliminated alternans. Steady state APD rate dependence was caused primarily by changes in [Na+]i, via its modulation of the electrogenic Na+/K+ ATPase current. At fast pacing rates, late Na+ current and ICaL were also contributors. APD shortening during restitution was primarily dependent on reduced late Na+ and ICa

  3. Escape to infinity under the action of a potential and a constant electromagnetic field

    CERN Document Server

    Gascon, F G

    2003-01-01

    Escape to infinity is proved for a great variety of potentials, including the potential created by an infinite number of sources. Relativistic escape is studied. Escape in the presence of a constant electromagnetic field and a potential is also considered.

  4. Age-Related Differences in the Visual Processes Implied in Perception and Action: Distance and Location Parameters

    Science.gov (United States)

    Rival, Christina; Olivier, Isabelle; Ceyte, Hadrien; Bard, Chantal

    2004-01-01

    The aim of the two present experiments was to examine the ontogenetic development of the dissociation between perception and action in children using the Duncker illusion. In this illusion, a moving background alters the perceived direction of target motion. Targets were held stationary while appearing to move in an induced displacement. In…

  5. Heteromeric Kv7.2/7.3 channels differentially regulate action potential initiation and conduction in neocortical myelinated axons.

    Science.gov (United States)

    Battefeld, Arne; Tran, Baouyen T; Gavrilis, Jason; Cooper, Edward C; Kole, Maarten H P

    2014-03-05

    Rapid energy-efficient signaling along vertebrate axons is achieved through intricate subcellular arrangements of voltage-gated ion channels and myelination. One recently appreciated example is the tight colocalization of K(v)7 potassium channels and voltage-gated sodium (Na(v)) channels in the axonal initial segment and nodes of Ranvier. The local biophysical properties of these K(v)7 channels and the functional impact of colocalization with Na(v) channels remain poorly understood. Here, we quantitatively examined K(v)7 channels in myelinated axons of rat neocortical pyramidal neurons using high-resolution confocal imaging and patch-clamp recording. K(v)7.2 and 7.3 immunoreactivity steeply increased within the distal two-thirds of the axon initial segment and was mirrored by the conductance density estimates, which increased from ~12 (proximal) to 150 pS μm(-2) (distal). The axonal initial segment and nodal M-currents were similar in voltage dependence and kinetics, carried by K(v)7.2/7.3 heterotetramers, 4% activated at the resting membrane potential and rapidly activated with single-exponential time constants (~15 ms at 28 mV). Experiments and computational modeling showed that while somatodendritic K(v)7 channels are strongly activated by the backpropagating action potential to attenuate the afterdepolarization and repetitive firing, axonal K(v)7 channels are minimally recruited by the forward-propagating action potential. Instead, in nodal domains K(v)7.2/7.3 channels were found to increase Na(v) channel availability and action potential amplitude by stabilizing the resting membrane potential. Thus, K(v)7 clustering near axonal Na(v) channels serves specific and context-dependent roles, both restraining initiation and enhancing conduction of the action potential.

  6. Role of action potential configuration and the contribution of Ca2+ and K+ currents to isoprenaline-induced changes in canine ventricular cells

    Science.gov (United States)

    Szentandrássy, N; Farkas, V; Bárándi, L; Hegyi, B; Ruzsnavszky, F; Horváth, B; Bányász, T; Magyar, J; Márton, I; Nánási, PP

    2012-01-01

    BACKGROUND AND PURPOSE Although isoprenaline (ISO) is known to activate several ion currents in mammalian myocardium, little is known about the role of action potential morphology in the ISO-induced changes in ion currents. Therefore, the effects of ISO on action potential configuration, L-type Ca2+ current (ICa), slow delayed rectifier K+ current (IKs) and fast delayed rectifier K+ current (IKr) were studied and compared in a frequency-dependent manner using canine isolated ventricular myocytes from various transmural locations. EXPERIMENTAL APPROACH Action potentials were recorded with conventional sharp microelectrodes; ion currents were measured using conventional and action potential voltage clamp techniques. KEY RESULTS In myocytes displaying a spike-and-dome action potential configuration (epicardial and midmyocardial cells), ISO caused reversible shortening of action potentials accompanied by elevation of the plateau. ISO-induced action potential shortening was absent in endocardial cells and in myocytes pretreated with 4-aminopyridine. Application of the IKr blocker E-4031 failed to modify the ISO effect, while action potentials were lengthened by ISO in the presence of the IKs blocker HMR-1556. Both action potential shortening and elevation of the plateau were prevented by pretreatment with the ICa blocker nisoldipine. Action potential voltage clamp experiments revealed a prominent slowly inactivating ICa followed by a rise in IKs, both currents increased with increasing the cycle length. CONCLUSIONS AND IMPLICATIONS The effect of ISO in canine ventricular cells depends critically on action potential configuration, and the ISO-induced activation of IKs– but not IKr– may be responsible for the observed shortening of action potentials. PMID:22563726

  7. Role of action potential configuration and the contribution of C²⁺a and K⁺ currents to isoprenaline-induced changes in canine ventricular cells.

    Science.gov (United States)

    Szentandrássy, N; Farkas, V; Bárándi, L; Hegyi, B; Ruzsnavszky, F; Horváth, B; Bányász, T; Magyar, J; Márton, I; Nánási, P P

    2012-10-01

    Although isoprenaline (ISO) is known to activate several ion currents in mammalian myocardium, little is known about the role of action potential morphology in the ISO-induced changes in ion currents. Therefore, the effects of ISO on action potential configuration, L-type Ca²⁺ current (I(Ca)), slow delayed rectifier K⁺ current (I(Ks)) and fast delayed rectifier K⁺ current (I(Kr)) were studied and compared in a frequency-dependent manner using canine isolated ventricular myocytes from various transmural locations. Action potentials were recorded with conventional sharp microelectrodes; ion currents were measured using conventional and action potential voltage clamp techniques. In myocytes displaying a spike-and-dome action potential configuration (epicardial and midmyocardial cells), ISO caused reversible shortening of action potentials accompanied by elevation of the plateau. ISO-induced action potential shortening was absent in endocardial cells and in myocytes pretreated with 4-aminopyridine. Application of the I(Kr) blocker E-4031 failed to modify the ISO effect, while action potentials were lengthened by ISO in the presence of the I(Ks) blocker HMR-1556. Both action potential shortening and elevation of the plateau were prevented by pretreatment with the I(Ca) blocker nisoldipine. Action potential voltage clamp experiments revealed a prominent slowly inactivating I(Ca) followed by a rise in I(Ks) , both currents increased with increasing the cycle length. The effect of ISO in canine ventricular cells depends critically on action potential configuration, and the ISO-induced activation of I(Ks) - but not I(Kr) - may be responsible for the observed shortening of action potentials. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  8. Consolidated Quarterly Report: Number of potential release sites subject to corrective action

    Energy Technology Data Exchange (ETDEWEB)

    Cochran, John R.; Cochran, John R.

    2017-04-01

    This Sandia National Laboratories, New Mexico Environmental Restoration Operations (ER) Consolidated Quarterly Report (ER Quarterly Report) fulfills all quarterly reporting requirements set forth in the Resource Conservation and Recovery Act Facility Operating Permit and the Compliance Order on Consent. The 12 sites in the corrective action process are listed in Table I-1.

  9. The Potential of General Classroom Observation: Turkish EFL Teachers' Perceptions, Sentiments, and Readiness for Action

    Science.gov (United States)

    Merç, Ali

    2015-01-01

    The purpose of this study was to determine Turkish EFL teachers' attitudes towards classroom observation. 204 teachers from different school settings responded to an online questionnaire. Data were analyzed according to three types of attitudes towards classroom observation: perceptions, sentiments, and readiness for action. The findings revealed…

  10. Acupuncture therapy: mechanism of action, efficacy, and safety: a potential intervention for psychogenic disorders?

    Science.gov (United States)

    2014-01-01

    Scientific bases for the mechanism of action of acupuncture in the treatment of pain and the pathogenic mechanism of acupuncture points are briefly summarized. The efficacy and safety of acupuncture therapy is discussed based on the results of German clinical trials. A conclusion on the role for acupuncture in the treatment of psychogenic disorders could not be reached. PMID:24444292

  11. Doubts about actions and flanker incongruity-related potentials and performance

    NARCIS (Netherlands)

    Tops, Mattie; Wijers, Albertus A.

    2012-01-01

    The brain networks that are involved in flanker incongruity and error processing are also consistently implicated in mental disorders such as obsessive compulsive disorder (OCD) that feature increased "Doubts about Actions" (DaA) scores. In the present study we investigated whether DaA scores,

  12. Feature-specific event-related potential effects to action- and sound-related verbs during visual word recognition

    Directory of Open Access Journals (Sweden)

    Margot Popp

    2016-12-01

    Full Text Available Grounded cognition theories suggest that conceptual representations essentially depend on modality-specific sensory and motor systems. Feature-specific brain activation across different feature types such as action or audition has been intensively investigated in nouns, while feature-specific conceptual category differences in verbs mainly focused on body part specific effects. The present work aimed at assessing whether feature-specific event-related potential (ERP differences between action and sound concepts, as previously observed in nouns, can also be found within the word class of verbs. In Experiment 1, participants were visually presented with carefully matched sound and action verbs within a lexical decision task, which provides implicit access to word meaning and minimizes strategic access to semantic word features. Experiment 2 tested whether pre-activating the verb concept in a context phase, in which the verb is presented with a related context noun, modulates subsequent feature-specific action vs. sound verb processing within the lexical decision task. In Experiment 1, ERP analyses revealed a differential ERP polarity pattern for action and sound verbs at parietal and central electrodes similar to previous results in nouns. Pre-activation of the meaning of verbs in the preceding context phase in Experiment 2 resulted in a polarity-reversal of feature-specific ERP effects in the lexical decision task compared with Experiment 1. This parallels analogous earlier findings for primed action and sound related nouns. In line with grounded cognitions theories, our ERP study provides evidence for a differential processing of action and sound verbs similar to earlier observation for concrete nouns. Although the localizational value of ERPs must be viewed with caution, our results indicate that the meaning of verbs is linked to different neural circuits depending on conceptual feature relevance.

  13. Encoding of point of view during action observation in the local field potentials of macaque area F5.

    Science.gov (United States)

    Caggiano, Vittorio; Giese, Martin; Thier, Peter; Casile, Antonino

    2015-02-01

    The discovery of mirror neurons compellingly shows that the monkey premotor area F5 is active not only during the execution but also during the observation of goal-directed motor acts. Previous studies have addressed the functioning of the mirror-neuron system at the single-unit level. Here, we tackled this research question at the network level by analysing local field potentials in area F5 while the monkey was presented with goal-directed actions executed by a human or monkey actor and observed either from a first-person or third-person perspective. Our analysis showed that rhythmic responses are not only present in area F5 during action observation, but are also modulated by the point of view. Observing an action from a subjective point of view produced significantly higher power in the low-frequency band (2-10 Hz) than observing the same action from a frontal view. Interestingly, an increase in power in the 2-10 Hz band was also produced by the execution of goal-directed motor acts. Independently of the point of view, action observation also produced a significant decrease in power in the 15-40 Hz band and an increase in the 60-100 Hz band. These results suggest that, depending on the point of view, action observation might activate different processes in area F5. Furthermore, they may provide information about the functional architecture of action perception in primates. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  14. Real time estimation of generation, extinction and flow of muscle fibre action potentials in high density surface EMG.

    Science.gov (United States)

    Mesin, Luca

    2015-02-01

    Developing a real time method to estimate generation, extinction and propagation of muscle fibre action potentials from bi-dimensional and high density surface electromyogram (EMG). A multi-frame generalization of an optical flow technique including a source term is considered. A model describing generation, extinction and propagation of action potentials is fit to epochs of surface EMG. The algorithm is tested on simulations of high density surface EMG (inter-electrode distance equal to 5mm) from finite length fibres generated using a multi-layer volume conductor model. The flow and source term estimated from interference EMG reflect the anatomy of the muscle, i.e. the direction of the fibres (2° of average estimation error) and the positions of innervation zone and tendons under the electrode grid (mean errors of about 1 and 2mm, respectively). The global conduction velocity of the action potentials from motor units under the detection system is also obtained from the estimated flow. The processing time is about 1 ms per channel for an epoch of EMG of duration 150 ms. A new real time image processing algorithm is proposed to investigate muscle anatomy and activity. Potential applications are proposed in prosthesis control, automatic detection of optimal channels for EMG index extraction and biofeedback. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Reactive species modify NaV1.8 channels and affect action potentials in murine dorsal root ganglion neurons.

    Science.gov (United States)

    Schink, Martin; Leipold, Enrico; Schirmeyer, Jana; Schönherr, Roland; Hoshi, Toshinori; Heinemann, Stefan H

    2016-01-01

    Dorsal root ganglion (DRG) neurons are important relay stations between the periphery and the central nervous system and are essential for somatosensory signaling. Reactive species are produced in a variety of physiological and pathophysiological conditions and are known to alter electric signaling. Here we studied the influence of reactive species on the electrical properties of DRG neurons from mice with the whole-cell patch-clamp method. Even mild stress induced by either low concentrations of chloramine-T (10 μM) or low-intensity blue light irradiation profoundly diminished action potential frequency but prolonged single action potentials in wild-type neurons. The impact on evoked action potentials was much smaller in neurons deficient of the tetrodotoxin (TTX)-resistant voltage-gated sodium channel NaV1.8 (NaV1.8(-/-)), the channel most important for the action potential upstroke in DRG neurons. Low concentrations of chloramine-T caused a significant reduction of NaV1.8 peak current and, at higher concentrations, progressively slowed down inactivation. Blue light had a smaller effect on amplitude but slowed down NaV1.8 channel inactivation. The observed effects were less apparent for TTX-sensitive NaV channels. NaV1.8 is an important reactive-species-sensitive component in the electrical signaling of DRG neurons, potentially giving rise to loss-of-function and gain-of-function phenomena depending on the type of reactive species and their effective concentration and time of exposure.

  16. The potential for multi-disciplinary primary health care services to take action on the social determinants of health: actions and constraints.

    Science.gov (United States)

    Baum, Frances E; Legge, David G; Freeman, Toby; Lawless, Angela; Labonté, Ronald; Jolley, Gwyneth M

    2013-05-10

    The Commission on the Social Determinants of Health and the World Health Organization have called for action to address the social determinants of health. This paper considers the extent to which primary health care services in Australia are able to respond to this call. We report on interview data from an empirical study of primary health care centres in Adelaide and Alice Springs, Australia. Sixty-eight interviews were held with staff and managers at six case study primary health care services, regional health executives, and departmental funders to explore how their work responded to the social determinants of health and the dilemmas in doing so. The six case study sites included an Aboriginal Community Controlled Organisation, a sexual health non-government organisation, and four services funded and managed by the South Australian government. While respondents varied in the extent to which they exhibited an understanding of social determinants most were reflexive about the constraints on their ability to take action. Services' responses to social determinants included delivering services in a way that takes account of the limitations individuals face from their life circumstances, and physical spaces in the primary health care services being designed to do more than simply deliver services to individuals. The services also undertake advocacy for policies that create healthier communities but note barriers to them doing this work. Our findings suggest that primary health care workers are required to transverse "dilemmatic space" in their work. The absence of systematic supportive policy, frameworks and structure means that it is hard for PHC services to act on the Commission on the Social Determinants of Health's recommendations. Our study does, however, provide evidence of the potential for PHC services to be more responsive to social determinants given more support and by building alliances with communities and social movements. Further research on the value

  17. Microelectrode array measurement of potassium ion channel remodeling on the field action potential duration in rapid atrial pacing rabbits model.

    Science.gov (United States)

    Sun, Juan; Yan, Huang; Wugeti, Najina; Guo, Yujun; Zhang, Ling; Ma, Mei; Guo, Xingui; Jiao, Changan; Xu, Wenli; Li, Tianqi

    2015-01-01

    Atrial fibrillation (AF) arises from abnormalities in atrial structure and electrical activity. Microelectrode arrays (MEA) is a real-time, nondestructive measurement of the resting and action potential signal, from myocardial cells, to the peripheral circuit of electrophysiological activity. This study examined the field action potential duration (fAPD) of the right atrial appendage (RAA) by MEA in rapid atrial pacing (RAP) in the right atrium of rabbits. In addition, this study also investigated the effect of potassium ion channel blockers on fAPD. 40 New Zealand white rabbits of either sex were randomly divided into 3 groups: 1) the control, 2) potassium ion channel blocker (TEA, 4-Ap and BaCl2), and 3) amiodarone groups. The hearts were quickly removed and right atrial appendage sectioned (slice thickness 500 μm). Each slice was perfused with Tyrode's solution and continuously stimulated for 30 minutes. Sections from the control group were superfused with Tyrode's solution for 10 minutes, while the blocker groups and amiodarone were both treated with their respective compounds for 10 minutes each. The fAPD of RAA and action field action potential morphology were measured using MEA. In non-pace (control) groups, fAPD was 188.33 ± 18.29 ms after Tyrode's solution superfusion, and 173.91 ± 6.83 ms after RAP. In pace/potassium ion channel groups, TEA and BaCl2 superfusion prolonged atrial field action potential (fAPD) (control vs blocker: 176.67 ± 8.66 ms vs 196.11 ± 10.76 ms, 182.22 ± 12.87 ms vs 191.11 ± 13.09 ms with TEA and BaCl2 superfusion, respectively, P action potential in animal heart slices. After superfusing potassium ion channel blockers, fAPD was prolonged. These results suggest that Ito, IKur and IK1 remodel and mediate RAP-induced atrial electrical remodeling. Amiodarone alter potassium ion channel activity (Ito, IKur, IK1 and IKs), shortening fAPD.

  18. Assessing transformational change potential: the case of the Tunisian cement Nationally Appropriate Mitigation Action (NAMA)

    DEFF Research Database (Denmark)

    Boodoo, Zyaad; Olsen, Karen Holm

    2018-01-01

    contributions (NDCs). However, there is still a scarcity of empirical studies on how transformational change policies and actions are designed and supported in practice. This article addresses such a gap in knowledge by combining theoretical insights from the multi-level perspective and transitions management......To effectively address the root causes of carbon lock-in across developing countries, Nationally Appropriate Mitigation Actions (NAMAs) with transformational change characteristics are being supported by donors and finance mechanisms as a means to achieve ambitious nationally determined...... literature to examine a donor-supported cement sector NAMA in Tunisia developed during 2012–2013. A narrative is constructed to analyse the adequacy of the NAMA design to promote structural shifts towards low carbon development in the cement sector. Data collection is based on semi-structured interviews...

  19. Potential Mechanisms of Action in the Treatment of Social Impairment and Disorganization in Adolescents with ADHD

    OpenAIRE

    Sadler, Joanna M.; Evans, Steven W.; Schultz, Brandon K.; Zoromski, Allison K.

    2011-01-01

    Two important domains that can be impaired in adolescents with ADHD are organization and social functioning; however, the development of interventions to target these areas in adolescents is in the early stages. Currently, small efficacy trials are beginning to be used to conduct preliminary tests on the proposed mechanisms of action for these interventions. These two studies examined the efficacy of organization and social functioning interventions for adolescents with ADHD...

  20. Sodium entry during action potentials of mammalian central neurons: incomplete inactivation and reduced metabolic efficiency in fast-spiking neurons

    OpenAIRE

    Carter, Brett C.; Bean, Bruce P.

    2009-01-01

    We measured the time course of sodium entry during action potentials of mouse central neurons at 37 °C to examine how efficiently sodium entry is coupled to depolarization. In cortical pyramidal neurons, sodium entry was nearly completely confined to the rising phase of the spike: only ~25% more sodium enters than the theoretical minimum necessary for spike depolarization. However, in fast-spiking GABAergic neurons (cerebellar Purkinje cells and cortical interneurons), twice as much sodium en...

  1. Ballistic parameters and trauma potential of direct-acting, powder-actuated fastening tools (nail guns).

    Science.gov (United States)

    Frank, Matthias; Franke, Ernst; Schönekess, Holger C; Jorczyk, Jörn; Bockholdt, Britta; Ekkernkamp, Axel

    2012-03-01

    Since their introduction in the 1950s in the construction and building trade, powder-actuated fastening tools (nail guns) are of forensic and traumatological importance. There are countless reports on both accidental and intentional injuries and fatalities caused by these tools in medical literature. While the ballistic parameters of so-called low-velocity fastening tools, where the expanding gases act on a captive piston that drives the fastener into the material, are well known, ballistic parameters of "high-velocity" tools, which operate like a firearm and release the energy of the propellant directly on the fastener, are unknown. Therefore, it was the aim of this work to investigate external ballistic parameters of cal. 9 and 6-mm fastening bolts discharged from four different direct-acting nail guns (Type Ideal, Record Piccolo S, Rapid Hammer R300, Titan Type 1). Average muzzle velocity ranged from 400 to 580 m/s, while average kinetic energy of the projectiles ranged from 385 to 547 J. Mean energy density of the projectiles ranged from 9 to 18 J/mm(2). To conclude, this work demonstrates that the muzzle velocity of direct-acting high-velocity tools is approximately five times higher than the muzzle velocity of piston-type tools. Hence, the much-cited comparison to the ballistic parameters of a cal. 22 handgun might be understated and a comparison to the widespread and well-known cal. 9 mm Luger might be more appropriate.

  2. Pupal and Adult Parameters as Potential Indicators of Cottonwood Leaf Beetle (Coleoptera: Chrysomelidae) Fecundity and Longevity

    Science.gov (United States)

    David R. Coyle; Joel D. McMillin; Elwood R. Hart

    1999-01-01

    Cottonwood leaf beetle, Chrysomela scripta, pupae from a laboratory colony were weighed and monitored through adult emergence, oviposition, and mortality to determine if correlations existed between various pupal or adult parameters and fecundity or longevity. Forty-three female cottonwood leaf beetles were monitored. Pupal weight was not a good...

  3. The nonlinear heat equation with state–dependent parameters and its connection to the Burgers’ and the potential Burgers’ equation

    DEFF Research Database (Denmark)

    Backi, Christoph Josef; Bendtsen, Jan Dimon; Leth, John-Josef

    2014-01-01

    In this work the stability properties of a nonlinear partial differential equation (PDE) with state–dependent parameters is investigated. Among other things, the PDE describes freezing of foodstuff, and is closely related to the (Potential) Burgers’ Equation. We show that for certain forms...

  4. A simulation of T-wave alternans vectocardiographic representation performed by changing the ventricular heart cells action potential duration.

    Science.gov (United States)

    Janusek, D; Kania, M; Zaczek, R; Zavala-Fernandez, H; Maniewski, R

    2014-04-01

    The presence of T wave alternans (TWA) in the surface ECG signals has been recognized as a marker of electrical instability, and is hypothesized to be related to patients at increased risk for ventricular arrhythmias. In this paper we present a TWA simulation study. The TWA phenomenon was simulated by changing the duration of the ventricular heart cells action potential. The magnitude was calculated in the surface ECG with the use of the time domain method. The spatially concordant TWA, where during one heart beat all ventricular cells display a short-duration action potential and during the next beat they exhibit a long-duration action potential, as well as the discordant TWA, where at least one region is out of phase, was simulated. The vectocardiographic representation was employed. The obtained results showed a high level of T-loop pattern and location disturbances connected to the discordant TWA simulation in contrast to the concordant one. This result may be explained by the spatial heterogeneity of the ventricular repolarization process, which could be higher for the discordant TWA than for the concordant TWA. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. Action potential changes associated with impairment of functional properties of sodium channels in hippocampal neurons induced by melamine.

    Science.gov (United States)

    Yang, Jia-Jia; Yang, Zhuo; Zhang, Tao

    2010-10-05

    Since the melamine-contamination event happened in September 2008, there have been lots of studies about melamine toxicity, but very limited studies focused on central nervous system (CNS). In the present study, we investigated the effects of melamine (5x10(-4), 5x10(-5) and 5x10(-6)g/ml) on voltage-gated sodium channels (VGSCs) in hippocampal CA1 neurons using whole-cell patch-clamp recordings technique. The results showed that only 5x10(-4)g/ml melamine reduced the amplitude of voltage-gated sodium current (I(Na)). At the concentrations of 5x10(-5) and 5x10(-4)g/ml, melamine produced a hyperpolarizing shift in the steady-state activation curve of I(Na) and also enhanced the steady-state inactivate processing of I(Na). Action potential properties and the pattern of repetitive firing were examined using current-clamp recording, which indicated that peak amplitude and overshoot of the evoked single action potential were decreased. The half-width and the firing rate of repetitive firing were increased in a concentration-dependent manner. The data suggest that melamine alters the action potential of hippocampal CA1 neurons by impairing the functional properties of VGSCs, which may be the underlie mechanisms of neurotoxicity induced by melamine. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  6. Carisbamate, a novel neuromodulator, inhibits voltage-gated sodium channels and action potential firing of rat hippocampal neurons.

    Science.gov (United States)

    Liu, Yi; Yohrling, George J; Wang, Yan; Hutchinson, Tasha L; Brenneman, Douglas E; Flores, Christopher M; Zhao, Boyu

    2009-01-01

    Carisbamate (RWJ-333369; (S)-2-O-carbamoyl-1-o-chlorophenyl-ethanol) is a novel investigational antiepileptic drug that exhibits a broad-spectrum of activity in a number of animal models of seizure and drug refractory epilepsy. In an effort to understand the molecular mechanism by which carisbamate produces its antiepileptic actions, we studied its effects on the function of voltage-gated, rat brain sodium and potassium channels and on the repetitive firing of action potentials in cultured rat hippocampal neurons. In whole-cell patch clamp recording, carisbamate resulted in a concentration-, voltage- and use-dependent inhibition of rat Nav1.2, with an IC(50) value of 68 microM at -67 mV. In rat hippocampal neurons, carisbamate similarly blocked voltage-gated sodium channels, with an IC(50) value of 89 microM at -67 mV, and inhibited repetitive firing of action potentials in a concentration-dependent manner (by 46% at 30 microM and 87% at 100 microM, respectively). Carisbamate had no effect on the steady-state membrane potential or voltage-gated potassium channels (K(v)) in these neurons. These inhibitory effects of carisbamate occurred at therapeutically relevant concentrations in vivo, raising the possibility that block of voltage-gated sodium channels by carisbamate contributes to its antiepileptic activity.

  7. Comment on "Penetration of Action Potentials During Collision in the Median and Lateral Giant Axons of Invertebrates"

    Science.gov (United States)

    Berg, Rune W.; Stauning, Marius Tving; Sørensen, Jakob Balslev; Jahnsen, Henrik

    2017-04-01

    The action potential (AP) is an electrical impulse elicited by depolarization of the neuronal membrane from the resting membrane potential (around -70 mV ). It propagates along the axon, allowing for rapid and distant communication. Recently, it was claimed that two APs traveling in opposite direction will pass unhindered through each other (penetrate) upon collision [Gonzalez-Perez et al.Phys. Rev. X 4, 031047 (2014), 10.1103/PhysRevX.4.031047]. We tested this claim under carefully controlled conditions and found that we cannot reproduce penetration. Instead, APs consistently annihilated upon collision. This is consistent with a vast body of literature.

  8. Two-Photon Na+ Imaging Reports Somatically Evoked Action Potentials in Rat Olfactory Bulb Mitral and Granule Cell Neurites.

    Science.gov (United States)

    Ona-Jodar, Tiffany; Gerkau, Niklas J; Sara Aghvami, S; Rose, Christine R; Egger, Veronica

    2017-01-01

    Dendrodendritic synaptic interactions are a hallmark of neuronal processing in the vertebrate olfactory bulb. Many classes of olfactory bulb neurons including the principal mitral cells (MCs) and the axonless granule cells (GCs) dispose of highly efficient propagation of action potentials (AP) within their dendrites, from where they can release transmitter onto each other. So far, backpropagation in GC dendrites has been investigated indirectly via Ca2+ imaging. Here, we used two-photon Na+ imaging to directly report opening of voltage-gated sodium channels due to AP propagation in both cell types. To this end, neurons in acute slices from juvenile rat bulbs were filled with 1 mM SBFI via whole-cell patch-clamp. Calibration of SBFI signals revealed that a change in fluorescence ΔF/F by 10% corresponded to a Δ[Na+]i of ∼22 mM. We then imaged proximal axon segments of MCs during somatically evoked APs (sAP). While single sAPs were detectable in ∼50% of axons, trains of 20 sAPs at 50 Hz always resulted in substantial ΔF/F of ∼15% (∼33 mM Δ[Na+]i). ΔF/F was significantly larger for 80 Hz vs. 50 Hz trains, and decayed with half-durations τ1/2 ∼0.6 s for both frequencies. In MC lateral dendrites, AP trains yielded small ΔF/F of ∼3% (∼7 mM Δ[Na+]i). In GC apical dendrites and adjacent spines, single sAPs were not detectable. Trains resulted in an average dendritic ΔF/F of 7% (16 mM Δ[Na+]i) with τ1/2 ∼1 s, similar for 50 and 80 Hz. Na+ transients were indistinguishable between large GC spines and their adjacent dendrites. Cell-wise analysis revealed two classes of GCs with the first showing a decrease in ΔF/F along the dendrite with distance from the soma and the second an increase. These classes clustered with morphological parameters. Simulations of Δ[Na+]i replicated these behaviors via negative and positive gradients in Na+ current density, assuming faithful AP backpropagation. Such specializations of dendritic excitability might confer

  9. A computational model of the ionic currents, Ca2+ dynamics and action potentials underlying contraction of isolated uterine smooth muscle.

    Directory of Open Access Journals (Sweden)

    Wing-Chiu Tong

    2011-04-01

    Full Text Available Uterine contractions during labor are discretely regulated by rhythmic action potentials (AP of varying duration and form that serve to determine calcium-dependent force production. We have employed a computational biology approach to develop a fuller understanding of the complexity of excitation-contraction (E-C coupling of uterine smooth muscle cells (USMC. Our overall aim is to establish a mathematical platform of sufficient biophysical detail to quantitatively describe known uterine E-C coupling parameters and thereby inform future empirical investigations of physiological and pathophysiological mechanisms governing normal and dysfunctional labors. From published and unpublished data we construct mathematical models for fourteen ionic currents of USMCs: Ca2+ currents (L- and T-type, Na+ current, an hyperpolarization-activated current, three voltage-gated K+ currents, two Ca2+-activated K+ current, Ca2+-activated Cl current, non-specific cation current, Na+-Ca2+ exchanger, Na+-K+ pump and background current. The magnitudes and kinetics of each current system in a spindle shaped single cell with a specified surface area:volume ratio is described by differential equations, in terms of maximal conductances, electrochemical gradient, voltage-dependent activation/inactivation gating variables and temporal changes in intracellular Ca2+ computed from known Ca2+ fluxes. These quantifications are validated by the reconstruction of the individual experimental ionic currents obtained under voltage-clamp. Phasic contraction is modeled in relation to the time constant of changing [Ca2+]i. This integrated model is validated by its reconstruction of the different USMC AP configurations (spikes, plateau and bursts of spikes, the change from bursting to plateau type AP produced by estradiol and of simultaneous experimental recordings of spontaneous AP, [Ca2+]i and phasic force. In summary, our advanced mathematical model provides a powerful tool to

  10. Determination of thermodynamic potentials and the aggregation number for micelles with the mass-action model by isothermal titration calorimetry

    DEFF Research Database (Denmark)

    Olesen, Niels Erik; Westh, Peter; Holm, René

    2015-01-01

    The aggregation number (n), thermodynamic potentials (ΔG, ΔH, ΔS) and critical micelle concentration (CMC) for 6 natural bile salts were determined on the basis of both original and previously published isothermal titration calorimetry (ITC) data. Different procedures to estimate parameters...

  11. Effects of muscle action type with equal impulse of conditioning activity on postactivation potentiation.

    Science.gov (United States)

    Bogdanis, Gregory C; Tsoukos, Athanasios; Veligekas, Panagiotis; Tsolakis, Charilaos; Terzis, Gerasimos

    2014-09-01

    This study investigated the effects of muscle action type during conditioning activity (half-squat) on subsequent vertical jump performance. Fourteen track and field athletes (relative half-squat of 2.3 ± 0.3 times their body weight) completed 4 main trials in a randomized and counterbalanced order 5-7 days apart: (a) concentric (CON) half-squats: 7.5 ± 1.2 repetitions against 90% of 1 repetition maximum (1RM), (b) eccentric (ECC) half-squats: 9.3 ± 1.5 repetitions against 70% of 1RM, and (c) 3 sets of 3-second maximal isometric (ISO) half-squats, (d) a control (CTRL) trial, where subjects rested for 10 minutes. The number of repetitions in CON and ECC was adjusted so that the impulse of the vertical ground reaction force was similar to ISO. Countermovement vertical jump (CMJ) performance was evaluated for 21 minutes after each main trial. Countermovement vertical jump performance in ISO was higher than CTRL from the second to the 10th minute of recovery, whereas CMJ performance in ECC was higher than CTRL from the sixth and 10th minute of recovery. Analysis of the peak individual responses revealed an increase in CMJ performance compared with baseline only in ISO (3.0 ± 1.2%; p = 0.045), whereas no significant increases were observed in ECC and CON. Peak CMJ performance for all subjects in ISO and ECC was achieved within 2-10 minutes after the conditioning muscle actions. Isometric were more effective than CON and ECC muscle actions in increasing explosive leg performance when the impulse of the ground reaction force of the conditioning exercise was equated.

  12. Anaesthetics stop diverse plant organ movements, affect endocytic vesicle recycling and ROS homeostasis, and block action potentials in Venus flytraps.

    Science.gov (United States)

    Yokawa, K; Kagenishi, T; Pavlovic, A; Gall, S; Weiland, M; Mancuso, S; Baluška, F

    2017-12-11

    Anaesthesia for medical purposes was introduced in the 19th century. However, the physiological mode of anaesthetic drug actions on the nervous system remains unclear. One of the remaining questions is how these different compounds, with no structural similarities and even chemically inert elements such as the noble gas xenon, act as anaesthetic agents inducing loss of consciousness. The main goal here was to determine if anaesthetics affect the same or similar processes in plants as in animals and humans. A single-lens reflex camera was used to follow organ movements in plants before, during and after recovery from exposure to diverse anaesthetics. Confocal microscopy was used to analyse endocytic vesicle trafficking. Electrical signals were recorded using a surface AgCl electrode. Mimosa leaves, pea tendrils, Venus flytraps and sundew traps all lost both their autonomous and touch-induced movements after exposure to anaesthetics. In Venus flytrap, this was shown to be due to the loss of action potentials under diethyl ether anaesthesia. The same concentration of diethyl ether immobilized pea tendrils. Anaesthetics also impeded seed germination and chlorophyll accumulation in cress seedlings. Endocytic vesicle recycling and reactive oxygen species (ROS) balance, as observed in intact Arabidopsis root apex cells, were also affected by all anaesthetics tested. Plants are sensitive to several anaesthetics that have no structural similarities. As in animals and humans, anaesthetics used at appropriate concentrations block action potentials and immobilize organs via effects on action potentials, endocytic vesicle recycling and ROS homeostasis. Plants emerge as ideal model objects to study general questions related to anaesthesia, as well as to serve as a suitable test system for human anaesthesia.

  13. Potentiation of E-4031-induced torsade de pointes by HMR1556 or ATX-II is not predicted by action potential short-term variability or triangulation.

    Science.gov (United States)

    Michael, G; Dempster, J; Kane, K A; Coker, S J

    2007-12-01

    Torsade de pointes (TdP) can be induced by a reduction in cardiac repolarizing capacity. The aim of this study was to assess whether IKs blockade or enhancement of INa could potentiate TdP induced by IKr blockade and to investigate whether short-term variability (STV) or triangulation of action potentials preceded TdP. Experiments were performed in open-chest, pentobarbital-anaesthetized, alpha 1-adrenoceptor-stimulated, male New Zealand White rabbits, which received three consecutive i.v. infusions of either the IKr blocker E-4031 (1, 3 and 10 nmol kg(-1) min(-1)), the IKs blocker HMR1556 (25, 75 and 250 nmol kg(-1) min(-1)) or E-4031 and HMR1556 combined. In a second study rabbits received either the same doses of E-4031, the INa enhancer, ATX-II (0.4, 1.2 and 4.0 nmol kg(-1)) or both of these drugs. ECGs and epicardial monophasic action potentials were recorded. HMR1556 alone did not cause TdP but increased E-4031-induced TdP from 25 to 80%. ATX-II alone caused TdP in 38% of rabbits, as did E-4031; 75% of rabbits receiving both drugs had TdP. QT intervals were prolonged by all drugs but the extent of QT prolongation was not related to the occurrence of TdP. No changes in STV were detected and triangulation was only increased after TdP occurred. Giving modulators of ion channels in combination substantially increased TdP but, in this model, neither STV nor triangulation of action potentials could predict TdP.

  14. Biphasic response of action potential duration to metabolic inhibition in rabbit and human ventricular myocytes: role of transient outward current and ATP-regulated potassium current

    NARCIS (Netherlands)

    Verkerk, A. O.; Veldkamp, M. W.; van Ginneken, A. C.; Bouman, L. N.

    1996-01-01

    Inhibition of cell metabolism is associated with significant changes in action potential duration. The aim of this study was to investigate the time course of the changes in action potential duration during metabolic inhibition and to determine what changes in membrane currents are responsible. The

  15. Remote Monitoring of the Heart Condition of Athletes by Measuring the Cardiac Action Potential Propagation Time Using a Wireless Sensor Network

    Directory of Open Access Journals (Sweden)

    Amang Sudarsono

    2016-04-01

    Full Text Available Highly performing athletes are susceptible to cardiac damage of several kinds which may be irreversible. The monitoring of heart rate and ECG waveforms from such subjects by wireless sensor networks has been reported in health and sports care documents. However, a more decisive parameter for instant to instant changes would be the time of Cardiac Action Potential Propagation. This time, which can be between 15-20 ms would shoot suddenly in acute stress in highly performing athletes for short durations. Repeated incidents of such rising values will tend to cause irreversible damage to the heart. We developed the technique of measuring this time and reporting it through a wireless sensor network to monitoring station.

  16. The Potential of Leptin for Treating Diabetes and Its Mechanism of Action

    Science.gov (United States)

    Coppari, Roberto; Bjørbæk, Christian

    2014-01-01

    Following the discovery of leptin in 1994, major research efforts have brought us much closer to a fuller understanding of the cellular and molecular mechanisms underlying the biological effects of the hormone. Interestingly, leptin exerts potent anti-diabetic actions that are independent of its effects on body weight and food intake. In particular, leptin can correct diabetes in animal models of either diabetes mellitus type 1 (T1DM) or type 2 (T2DM). In addition, long-term leptin-replacement therapy is well tolerated and dramatically improves glycemic control, insulin sensitivity, and plasma triglycerides in patients with severe insulin resistance due to lipodystrophy. Together, these results have spurred enthusiasm for the use of leptin therapy to treat humans suffering from diabetes mellitus. Here, we review current understandings of these glucoregulatory functions of leptin, with particular emphasis on its central mechanisms of action, lessons from clinical studies and discuss possible therapeutic applications of leptin in the treatment of T1DM and T2DM. PMID:22935803

  17. Action potential-based MEA platform for in vitro screening of drug-induced cardiotoxicity using human iPSCs and rat neonatal myocytes.

    Science.gov (United States)

    Jans, Danny; Callewaert, Geert; Krylychkina, Olga; Hoffman, Luis; Gullo, Francesco; Prodanov, Dimiter; Braeken, Dries

    2017-09-01

    Drug-induced cardiotoxicity poses a negative impact on public health and drug development. Cardiac safety pharmacology issues urged for the preclinical assessment of drug-induced ventricular arrhythmia leading to the design of several in vitro electrophysiological screening assays. In general, patch clamp systems allow for intracellular recordings, while multi-electrode array (MEA) technology detect extracellular activity. Here, we demonstrate a complementary metal oxide semiconductor (CMOS)-based MEA system as a reliable platform for non-invasive, long-term intracellular recording of cardiac action potentials at high resolution. Quinidine (8 concentrations from 10 -7 to 2.10 -5 M) and verapamil (7 concentrations from 10 -11 to 10 -5 M) were tested for dose-dependent responses in a network of cardiomyocytes. Electrophysiological parameters, such as the action potential duration (APD), rates of depolarization and repolarization and beating frequency were assessed. In hiPSC, quinidine prolonged APD with EC 50 of 2.2·10 -6 M. Further analysis indicated a multifactorial action potential prolongation by quinidine: (1) decreasing fast repolarization with IC 50 of 1.1·10 -6 M; (2) reducing maximum upstroke velocity with IC 50 of 2.6·10 -6 M; and (3) suppressing spontaneous activity with EC 50 of 3.8·10 -6 M. In rat neonatal cardiomyocytes, verapamil blocked spontaneous activity with EC 50 of 5.3·10 -8 M and prolonged the APD with EC 50 of 2.5·10 -8 M. Verapamil reduced rates of fast depolarization and repolarization with IC 50 s of 1.8 and 2.2·10 -7 M, respectively. In conclusion, the proposed action potential-based MEA platform offers high quality and stable long-term recordings with high information content allowing to characterize multi-ion channel blocking drugs. We anticipate application of the system as a screening platform to efficiently and cost-effectively test drugs for cardiac safety. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Contribution of I Kr and I K1 to ventricular repolarization in canine and human myocytes: is there any influence of action potential duration?

    Science.gov (United States)

    Jost, Norbert; Acsai, Károly; Horváth, Balázs; Bányász, Tamás; Baczkó, István; Bitay, Miklós; Bogáts, Gábor; Nánási, Péter P

    2009-01-01

    The aim of the present work was to study the profile of the rapid delayed rectifier potassium current (I (Kr)) and the inward rectifier potassium current (I (K1)) during ventricular repolarization as a function of action potential duration and rate of repolarization. Whole cell configuration of the patch clamp technique was used to monitor I (Kr) and I (K1) during the action potential plateau and terminal repolarization. Action potentials recorded at various cycle lengths (0.4-5 s) and repolarizing voltage ramps having various slopes (0.5-3 V/s) were used as command signals. I (Kr) and I (K1) were identified as difference currents dissected by E-4031 and BaCl(2), respectively. Neither peak amplitudes nor mean values of I (Kr) and I (K1) recorded during the plateau of canine action potentials were influenced by action potential duration. The membrane potential where I (Kr) and I (K1) peaked during the terminal repolarization was also independent of action potential duration. Similar results were obtained in undiseased human ventricular myocytes, and also in canine cells when I (Kr) and I (K1) were evoked using repolarizing voltage ramps of various slopes. Action potential voltage clamp experiments revealed that the peak values of I (Kr), I (K1), and net outward current during the terminal repolarization were independent of the pacing cycle length within the range of 0.4 and 5 s. The results indicate that action potential configuration fails to influence the amplitude of I (Kr) and I (K1) during the ventricular action potential in dogs and humans, suggesting that rate-dependent changes in action potential duration are not likely related to rate-dependent alterations in I (Kr) or I (K1) kinetics in these species.

  19. Pathological prolongation of action potential duration as a cause of the reduced alpha-adrenoceptor-mediated negative inotropy in streptozotocin-induced diabetic mice myocardium.

    Science.gov (United States)

    Kanae, Haruna; Hamaguchi, Shogo; Wakasugi, Yumi; Kusakabe, Taichi; Kato, Keisuke; Namekata, Iyuki; Tanaka, Hikaru

    2017-11-01

    Effect of pathological prolongation of action potential duration on the α-adrenoceptor-mediated negative inotropy was studied in streptozotocin-induced diabetic mice myocardium. In streptozotocin-treated mouse ventricular myocardium, which had longer duration of action potential than that in control mice, the negative inotropic response induced by phenylephrine was smaller than that in control mice. 4-Aminopyridine prolonged the action potential duration and decreased the negative inotropy in control mice. Cromakalim shortened the action potential duration and increased the negative inotropy in streptozotocin-treated mice. These results suggest that the reduced α-adrenoceptor-mediated inotropy in the diabetic mouse myocardium is partly due to its prolonged action potential. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  20. Human native Cav1 channels in chromaffin cells: contribution to exocytosis and firing of spontaneous action potentials.

    Science.gov (United States)

    Hernández-Vivanco, Alicia; Sanz-Lázaro, Sara; Jiménez-Pompa, Amanda; García-Magro, Nuria; Carmona-Hidalgo, Beatriz; Pérez-Alvarez, Alberto; Caba-González, Jose Carlos; Tabernero, Angel; Alonso Y Gregorio, Sergio; Passas, Juan; Blázquez, Jesús; González-Enguita, Carmen; de Castro-Guerín, Cristina; Albillos, Almudena

    2017-02-05

    The present study was performed to evaluate the Ca v 1 channel subtypes expressed in human chromaffin cells and the role that these channels play in exocytosis and cell excitability. Here we show that human chromaffin cells obtained from organ donors express Ca v 1.2 and Ca v 1.3 subtypes using molecular and pharmacological techniques. Immunocytochemical data demonstrated the presence of Ca v 1.2 and Ca v 1.3 subtypes, but not Ca v 1.1 or Ca v 1.4. Electrophysiological experiments were conducted to investigate the contribution of Ca v 1 channels to the exocytotic process and cell excitability. Ca v 1 channels contribute to the exocytosis of secretory vesicles, evidenced by the block of 3μM nifedipine (36.5±2%) of membrane capacitance increment elicited by 200ms depolarizing pulses. These channels show a minor contribution to the initiation of spontaneous action potential firing, as shown by the 2.5 pA of current at the threshold potential (-34mV), which elicits 10.4mV of potential increment. In addition, we found that only 8% of human chromaffin cells exhibit spontaneous action potentials. These data offer novel information regarding human chromaffin cells and the role of human native Ca v 1 channels in exocytosis and cell excitability. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. The corneoscleral shell of the eye: potentials of assessing biomechanical parameters in normal and pathological conditions

    Directory of Open Access Journals (Sweden)

    E. N. Iomdina

    2016-01-01

    Full Text Available The paper reviews modern methods of evaluating the biomechanical properties of the corneoscleral shell of the eye that can be used both in the studies of the pathogenesis of various ophthalmic pathologies and in clinical practice. The biomechanical parameters of the cornea and the sclera have been shown to be diagnostically significant in assessing the risk of complications and the effectiveness of keratorefractive interventions, in the diagnosis and the prognosis of keratoconus, progressive myopia, or glaucoma. In clinical practice, a special device, Ocular Response Analyzer (ORA, has been used on a large scale. The analyzer is used to assess two parameters that characterize viscoelastic properties of the cornea — corneal hysteresis (CH and corneal resistance factor (CRF. Reduced levels of CH and CRF have been noted after eximer laser surgery, especially that administered to patients who demonstrate a regression in the refraction effect or suffer from keratoconus. This fact justifies the use of these biomechanical parameters as additional diagnostic criteria in the evaluation of the state of the cornea. At the same time, ORA data are shown to reflect the biomechanical response to the impact of the air pulse not only from the cornea alone but also from the whole corneoscleral capsule. This is probably the cause of reduced CH in children with progressive myopia and a weakened supportive function of the sclera, as well as such reduction in glaucomatous adult patients. It is hypothesized that a low CH value is a result of remodeling of the connective tissue matrix of the corneoscleral shell of the eye and can be an independent factor testifying to a risk of glaucoma progression. Reduced CH in primary open-angle glaucoma occurs in parallel with the development of pathological structural changes of the optic disc, and deterioration of visual fields, which is an evidence of a specific character and sensitivity of this parameter. The

  2. [Molecular-kinetic parameters of thiamine enzymes and the mechanism of antivitamin action of hydroxythiamine in animal organisms].

    Science.gov (United States)

    Ostrovskiĭ KuM; Voskoboev, A I; Gorenshtenĭn, B I; Dosta, G A

    1979-09-01

    The molecula-kinetic parameters (Km, Ki) of three thiamine enzymes, e. g. thiamine pyrophosphokinase (EC 2.7.6.2), pyruvate dehydrogenase (EC 1.2.4.1) and transketolase (EC 2.2.1.1) with respect to the effects of the thiamine antimetabolite hydroxythiamine in the whole animal organism have been compared. It has been shown that only the first two enzymes, which interact competitively with the vitamin, antivitamin or their pyrophosphate ethers, obey the kinetic parameters obtained for the purified enzymes in vitro. The anticoenzymic effect of hydroxythiamine pyrophosphate with respect to transketolase is not observed in vivo at maximal concentration of the anticoenzyme in tissues due to the absence of competitive interactions with thiamine pyrophosphate. The incorporation of the true and false coenzymes into transketolase occurs only during de novo transketolase synthesis (the apoform is absent in tissues, with the exception of erythrocytes) and proceeds slowly with a half-life time equal to 24--30 hrs. After a single injection of hydroxythiamine at a large dose (70--400 mg/kg) the maximal inhibition of the transketolase activity in tissues (liver, heart, kidney, muscle, spleen, lungs adrenal grands) manifests itself by the 48th--72nd hour, when the concentration of free hydroxythiamine and its pyrophosphate is minimal and the whole anticoenzyme is tightly bound to the protein, forming the false holoenzyme. The use of hydroxythiamine for inhibition of pyruvate dehydrogenase or transketolase in animal organism is discussed.

  3. Waveform Similarity Analysis: A Simple Template Comparing Approach for Detecting and Quantifying Noisy Evoked Compound Action Potentials.

    Directory of Open Access Journals (Sweden)

    Jason Robert Potas

    Full Text Available Experimental electrophysiological assessment of evoked responses from regenerating nerves is challenging due to the typical complex response of events dispersed over various latencies and poor signal-to-noise ratio. Our objective was to automate the detection of compound action potential events and derive their latencies and magnitudes using a simple cross-correlation template comparison approach. For this, we developed an algorithm called Waveform Similarity Analysis. To test the algorithm, challenging signals were generated in vivo by stimulating sural and sciatic nerves, whilst recording evoked potentials at the sciatic nerve and tibialis anterior muscle, respectively, in animals recovering from sciatic nerve transection. Our template for the algorithm was generated based on responses evoked from the intact side. We also simulated noisy signals and examined the output of the Waveform Similarity Analysis algorithm with imperfect templates. Signals were detected and quantified using Waveform Similarity Analysis, which was compared to event detection, latency and magnitude measurements of the same signals performed by a trained observer, a process we called Trained Eye Analysis. The Waveform Similarity Analysis algorithm could successfully detect and quantify simple or complex responses from nerve and muscle compound action potentials of intact or regenerated nerves. Incorrectly specifying the template outperformed Trained Eye Analysis for predicting signal amplitude, but produced consistent latency errors for the simulated signals examined. Compared to the trained eye, Waveform Similarity Analysis is automatic, objective, does not rely on the observer to identify and/or measure peaks, and can detect small clustered events even when signal-to-noise ratio is poor. Waveform Similarity Analysis provides a simple, reliable and convenient approach to quantify latencies and magnitudes of complex waveforms and therefore serves as a useful tool for

  4. Potential Molecular Mechanisms on the Role of the Sigma-1 Receptor in the Action of Cocaine and Methamphetamine.

    Science.gov (United States)

    Yasui, Yuko; Su, Tsung-Ping

    2016-02-20

    The sigma-1 receptor (Sig-1R) is an endoplasmic reticulum membrane protein that involves a wide range of physiological functions. The Sig-1R has been shown to bind psychostimulants including cocaine and methamphetamine (METH) and thus has been implicated in the actions of those psychostimulants. For example, it has been demonstrated that the Sig-1R antagonists mitigate certain behavioral and cellular effects of psychostimulants including hyperactivity and neurotoxicity. Thus, the Sig-1R has become a potential therapeutic target of medication development against drug abuse that differs from traditional monoamine-related strategies. In this review, we will focus on the molecular mechanisms of the Sig-1R and discuss in such a manner with a hope to further understand or unveil unexplored relations between the Sig-1R and the actions of cocaine and METH, particularly in the context of cellular biological relevance.

  5. Assessing potential targets of calcium action in light-modulated gravitropism

    Science.gov (United States)

    Roux, S. J.

    1995-01-01

    Light, through the mediation of the pigment phytochrome, modulates the gravitropic response of the shoots and roots of many plants. The transduction of both light and gravity stimuli appears to involve Ca(2+)-regulated steps, one or more of which may represent points of intersection between the two transduction chains. To be confident that Ca2+ plays a critical role in stimulus-response coupling for gravitropism, it will be important to identify specific targets of Ca2+ action whose function can be clearly linked to the regulation of growth. Calcium typically exerts its influence on cell metabolism through binding to and activating key regulatory proteins. The three best characterized of these proteins in plants are the calmodulins, calcium-dependent protein kinases, and annexins. In this review we summarize what is known about the structure and function of these proteins and speculate on how their activation by Ca2+ could influence the differential growth response of gravitropism.

  6. The human ether-a-go-go-related gene (hERG) current inhibition selectively prolongs action potential of midmyocardial cells to augment transmural dispersion.

    Science.gov (United States)

    Yasuda, C; Yasuda, S; Yamashita, H; Okada, J; Hisada, T; Sugiura, S

    2015-08-01

    The majority of drug induced arrhythmias are related to the prolongation of action potential duration following inhibition of rapidly activating delayed rectifier potassium current (I(Kr)) mediated by the hERG channel. However, for arrhythmias to develop and be sustained, not only the prolongation of action potential duration but also its transmural dispersion are required. Herein, we evaluated the effect of hERG inhibition on transmural dispersion of action potential duration using the action potential clamp technique that combined an in silico myocyte model with the actual I(Kr) measurement. Whole cell I(Kr) current was measured in Chinese hamster ovary cells stably expressing the hERG channel. The measured current was coupled with models of ventricular endocardial, M-, and epicardial cells to calculate the action potentials. Action potentials were evaluated under control condition and in the presence of 1, 10, or 100 μM disopyramide, an hERG inhibitor. Disopyramide dose-dependently increased the action potential durations of the three cell types. However, action potential duration of M-cells increased disproportionately at higher doses, and was significantly different from that of epicardial and endocardial cells (dispersion of repolarization). By contrast, the effects of disopyramide on peak I(Kr) and instantaneous current-voltage relation were similar in all cell types. Simulation study suggested that the reduced repolarization reserve of M-cell with smaller amount of slowly activating delayed rectifier potassium current levels off at longer action potential duration to make such differences. The action potential clamp technique is useful for studying the mechanism of arrhythmogenesis by hERG inhibition through the transmural dispersion of repolarization.

  7. Pyrolysis, kinetics analysis, thermodynamics parameters and reaction mechanism of Typha latifolia to evaluate its bioenergy potential.

    Science.gov (United States)

    Ahmad, Muhammad Sajjad; Mehmood, Muhammad Aamer; Taqvi, Syed Taha Haider; Elkamel, Ali; Liu, Chen-Guang; Xu, Jianren; Rahimuddin, Sawsan Abdulaziz; Gull, Munazza

    2017-12-01

    This work was focused on understanding the pyrolysis of Typha latifolia. Kinetics, thermodynamics parameters and pyrolysis reaction mechanism were studied using thermogravimetric data. Based on activation energies and conversion points, two regions of pyrolysis were established. Region-I occurred between the conversion rate 0.1-0.4 with peak temperatures 538K, 555K, 556K at the heating rates of 10Kmin-1, 30Kmin-1, and 50Kmin-1, respectively. Similarly, the Region-II occurred between 0.4 and 0.8 with peak temperatures of 606K, 621K, 623K at same heating rates. The best model was diffusion mechanism in Region-I. In Region-II, the reaction order was shown to be 2nd and 3rd. The values of activation energy calculated using FWO and KAS methods (134-204kJmol-1) remained same in both regions reflecting that the best reaction mechanism was predicted. Kinetics and thermodynamic parameters including E, ΔH, ΔS, ΔG shown that T. latifolia biomass is a remarkable feedstock for bioenergy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. The role of various parameters used in proximity potential in heavy ...

    Indian Academy of Sciences (India)

    The detailed inves- tigation of over 395 reactions reveal that the new proximity potential reproduces the experimental data better than earlier versions. Keywords. Nuclear reaction models and methods; fusion and fusion–fission reactions; fusion reactions; low and intermediate energy heavy-ion reactions. PACS Nos 24.10.

  9. Anti-atherogenic potential of jujube, saffron and barberry: anti-diabetic and antioxidant actions

    Science.gov (United States)

    Hemmati, Mina; Zohoori, Elham; Mehrpour, Omid; Karamian, Mehdi; Asghari, Somaye; Zarban, Asghar; Nasouti, Roya

    2015-01-01

    Atherogenic dyslipidemia, characterized by an increased level of lipoprotein (a) and a decreased level of adiponectin, is a major risk factor for cardiovascular diseases in diabetic patients. To reduce cardiovascular risk in diabetic patients, use of agents with antidiabetic and anti-atherogenic potential is required. Using an animal model of diabetes, we investigated the antiatherogenic potential of extracts of three medicinal plants: jujube, barberry, and saffron. For this, serum level of fasting blood glucose, lipid profile, malondialdehyde, total antioxidant capacity, adiponectin and lipoprotein (a) in diabetic control and extract treated groups were measured. Statistical analysis of measurements showed that serum levels of fasting blood glucose, triglyceride, and VLDL decreased significantly (P jujube extract. Jujube, saffron, and barberry extracts are beneficial in ameliorating oxidative stress and atherogenic risk of diabetic rats. This highlights the benefits of further investigating the cardio-protective potential of medicinal plant extracts and evaluating their usefulness as cardio protective agents in clinical practice. PMID:26600752

  10. Dynamic contrast enhanced MRI-derived parameters are potential biomarkers of therapeutic response in bladder carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Chakiba, Camille [Department of Medical Oncology, Bergonié Cancer Institute, Bordeaux (France); Cornelis, François [Department of Radiology, Pellegrin Hospital, Bordeaux (France); Descat, Edouard [Department of Radiology, Saint-Augustin Clinic, Bordeaux (France); Gross-Goupil, Marine [Department of Medical Oncology, Bergonié Cancer Institute, Bordeaux (France); Sargos, Paul [Department of Radiotherapy, Bergonié Cancer Institute, Bordeaux (France); Roubaud, Guilhem [Department of Medical Oncology, Bergonié Cancer Institute, Bordeaux (France); Houédé, Nadine, E-mail: nadine.houede@chu-nimes.fr [Department of Medical Oncology, Bergonié Cancer Institute, Bordeaux (France); Department of Medical Oncology, Nimes University Hosptital, Nîmes (France)

    2015-06-15

    Highlights: • DCE-MRI parameters could be useful biomarker for patients with localized bladder carcinoma. • Rate of relapse is lower for good responders assessed by DCE-MRI. • The use of DCE-MRI parameters may improve the standardization of patients’ selection before surgery. - Abstract: Objectives: To evaluate the performance of dynamic contrast enhanced (DCE) magnetic resonance (MR) imaging to assess the histological response after chemotherapy on bladder carcinoma. Methods: From 2008 to 2010, 12 patients presenting localized urothelial carcinoma of the bladder were prospectively evaluated by DCE-MR imaging before and after two courses of cisplatin-based neoadjuvant chemotherapy. Size and thickness of tumours were measured. Relative enhancement at the arterial (rSI{sub 35s}) and venous phases (rSI{sub 80s}) of each tumour was obtained. Histological response was assessed and outcomes were recorded. Results: Histological examination after neoadjuvant chemotherapy concluded as pathological complete response (pCR) for 6 out of 12 patients. Five patients developed recurrences (4/6 no pCR and 1/6 pCR). Significant differences, between before and after treatment, were found for patients with complete pathological response after chemotherapy for all MR quantitative values. Tumours decreased in size and thickness (both P = 0.03). After treatment, rSI{sub 80s} was significantly different between pCR and non-pCR patients (P = 0.04) with a cut-off value of 40%. For this cut-off, sensitivity, specificity and accuracy were 83.33%. Similar recurrence free survivals were obtained if applying the MR cut-off value or the histopathological findings. Conclusion: Our results suggest that DCE-MR imaging may be a useful biomarker for patients with localized bladder carcinoma, improving selection before surgery.

  11. Microbial volatile fongerprints : potential use for soil / water diagnostics and correlation with traditional microbial parameters

    OpenAIRE

    Bastos, A.C.

    2007-01-01

    This project used an electronic nose (E-nose) system composed of an array of 14 non- specific conducting polymer sensors for soil and water diagnostics, based on qualitative microbial volatile production patterns. It tested the feasibility of using soil microbial volatile fingerprints for detecting and monitoring changes in microbial activity in three soils, as a response to key environmental factors such as temperature (16, 25, 37°C), water potential (-0.7, -2.8 MPa), and nutr...

  12. The ionosphere plasma structural parameters investigation by a Langmuir cylindrical probe eliminating the spacecraft floating potential influence

    Science.gov (United States)

    Gousheva, Mariana; Angelov, Plamen; Hristov, Plamen; Kirov, Boyan; Georgieva, Katya

    The paper presents an analysis of some problems due to the influence of the spacecraft floating potential as well as the analyzing voltage at the ionosphere plasma structural parameters investigation by cylindrical Langmuir probe. A computer simulation using a new high-precision method for periodical measurement of the Langmuir cylindrical probe floating potential when measuring the probe collector current is presented. The advantages of the presented method, which is suitable for measurement of all parts of the V-A probe curve, are discussed.

  13. Novel experimental results in human cardiac electrophysiology: measurement of the Purkinje fibre action potential from the undiseased human heart.

    Science.gov (United States)

    Nagy, Norbert; Szél, Tamás; Jost, Norbert; Tóth, András; Gy Papp, Julius; Varró, András

    2015-09-01

    Data obtained from canine cardiac electrophysiology studies are often extrapolated to the human heart. However, it has been previously demonstrated that because of the lower density of its K(+) currents, the human ventricular action potential has a less extensive repolarization reserve. Since the relevance of canine data to the human heart has not yet been fully clarified, the aim of the present study was to determine for the first time the action potentials of undiseased human Purkinje fibres (PFs) and to compare them directly with those of dog PFs. All measurements were performed at 37 °C using the conventional microelectrode technique. At a stimulation rate of 1 Hz, the plateau potential of human PFs is more positive (8.0 ± 1.8 vs 8.6 ± 3.4 mV, n = 7), while the amplitude of the spike is less pronounced. The maximal rate of depolarization is significantly lower in human PKs than in canine PFs (406.7 ± 62 vs 643 ± 36 V/s, respectively, n = 7). We assume that the appreciable difference in the protein expression profiles of the 2 species may underlie these important disparities. Therefore, caution is advised when canine PF data are extrapolated to humans, and further experiments are required to investigate the characteristics of human PF repolarization and its possible role in arrhythmogenesis.

  14. Action-space Clustering of Tidal Streams to Infer the Galactic Potential

    NARCIS (Netherlands)

    E. Sanderson, Robyn; Helmi, Amina; W. Hogg, David

    We present a new method for constraining the Milky Way halo gravitational potential by simultaneously fitting multiple tidal streams. This method requires three-dimensional positions and velocities for all stars to be fit, but does not require identification of any specific stream or determination

  15. Potentiating action of propofol at GABAA receptors of retinal bipolar cells

    DEFF Research Database (Denmark)

    Yue, Lan; Xie, An; Bruzik, Karol S

    2011-01-01

    + propofol) led to a progressive increase in peak response amplitude and, at higher propofol concentrations, additional changes that included a prolonged time course of response recovery. Pre-exposure of the cell to perfusing propofol typically enhanced the rate of development of potentiation produced...

  16. Virtual Burglary: Exploring the Potential of Virtual Reality to Study Burglary in Action

    NARCIS (Netherlands)

    van Sintemaartensdijk, I.; van Prooijen, J-W.; van Gelder, J-L.; Otte, M.; Nee, Claire; Demetriou, Andrew

    2016-01-01

    Objectives: This article explores the potential of virtual reality (VR) to study burglary by measuring user responses on the subjective, physiological, and behavioral levels. Furthermore, it examines the influence of individual dispositions, such as sensation seeking and self-control, on behavior

  17. Loss of Local Astrocyte Support Disrupts Action Potential Propagation and Glutamate Release Synchrony from Unmyelinated Hippocampal Axon Terminals In Vitro.

    Science.gov (United States)

    Sobieski, Courtney; Jiang, Xiaoping; Crawford, Devon C; Mennerick, Steven

    2015-08-05

    Neuron-astrocyte interactions are critical for proper CNS development and function. Astrocytes secrete factors that are pivotal for synaptic development and function, neuronal metabolism, and neuronal survival. Our understanding of this relationship, however, remains incomplete due to technical hurdles that have prevented the removal of astrocytes from neuronal circuits without changing other important conditions. Here we overcame this obstacle by growing solitary rat hippocampal neurons on microcultures that were comprised of either an astrocyte bed (+astrocyte) or a collagen bed (-astrocyte) within the same culture dish. -Astrocyte autaptic evoked EPSCs, but not IPSCs, displayed an altered temporal profile, which included increased synaptic delay, increased time to peak, and severe glutamate release asynchrony, distinct from previously described quantal asynchrony. Although we observed minimal alteration of the somatically recorded action potential waveform, action potential propagation was altered. We observed a longer latency between somatic initiation and arrival at distal locations, which likely explains asynchronous EPSC peaks, and we observed broadening of the axonal spike, which likely underlies changes to evoked EPSC onset. No apparent changes in axon structure were observed, suggesting altered axonal excitability. In conclusion, we propose that local astrocyte support has an unappreciated role in maintaining glutamate release synchrony by disturbing axonal signal propagation. Certain glial cell types (oligodendrocytes, Schwann cells) facilitate the propagation of neuronal electrical signals, but a role for astrocytes has not been identified despite many other functions of astrocytes in supporting and modulating neuronal signaling. Under identical global conditions, we cultured neurons with or without local astrocyte support. Without local astrocytes, glutamate transmission was desynchronized by an alteration of the waveform and arrival time of axonal

  18. Effects of flecainide and quinidine on action potential and ventricular arrhythmogenic properties in Scn3b knockout mice.

    Science.gov (United States)

    Hakim, Parvez; Thresher, Rosemary; Grace, Andrew A; Huang, Christopher L-H

    2010-08-01

    1. Flecainide and quinidine exert contrasting pro-arrhythmic and anti-arrhythmic effects in mouse hearts containing the loss-of-function, Scn5a(+/-), and the gain-of-function, Scn5a(+/DeltaKPQ), mutations in their sodium channel alpha-subunits. 2. The following properties were accordingly compared in wild-type and Scn3b(-/-) hearts modelling modifications in the beta-subunit, before and after introduction of either agent: (i) ventricular arrhythmogenecity and effective refractory periods (VERP) in response to programmed electrical stimulation (PES); (ii) monophasic action potential waveforms recorded from the left ventricular epicardium and endocardium; (iii) action potential durations (APD) obtained from the monophasic action potentials; and (iv) critical intervals derived from the APD and VERP values. 3. Ventricular tachycardia was induced by PES in 11 out of 15 Scn3b(-/-) hearts and 0 out of 17 wild-type hearts. This incidence was reduced to three out of eight Scn3b(-/-) hearts but increased to three out of eight wild-type hearts with flecainide. 4. Arrhythmogenic incidence was reduced to two out of eight Scn3b(-/-) hearts and remained at 0 out of eight wild-type hearts in the presence of quinidine. 5. Ventricular effective refractory periods were prolonged and endocardial and epicardial APD shortened, resulting in negative critical intervals in both Scn3b(-/-) and wild-type hearts treated by either flecainide or quinidine. Nevertheless, endocardial APD remained consistently longer than epicardial APD, leaving similar, positive endocardial-epicardial, differences, DeltaAPD, in treated and untreated Scn3b(-/-) and wild-type hearts. 6. It is concluded that both flecainide and quinidine exert anti-arrhythmogenic effects in Scn3b(-/-) hearts, doing so through modifying VERP rather than DeltaAPD, in contrast to their differing effects in Scn5a(+/-) and Scn5a(+/DeltaKPQ) hearts.

  19. Frequency-dependent effects of phenytoin on the maximum upstroke velocity of action potentials in guinea-pig papillary muscles.

    Science.gov (United States)

    Kojima, M; Ichiyama, M; Ban, T

    1986-07-01

    Phenytoin, at 50 to 200 micrograms reduced the maximum upstroke velocity of action potentials (Vmax) with increases in frequency from 0.25 to 5 Hz and in the external potassium concentration [( K+]0) from 2.7 to 8.1 mM. The drug-induced shortening of action potential duration was evident at 0.25 to 2 Hz but little at 3 to 5 Hz. Time courses of recovery of Vmax was studied by applying premature responses between the conditioning responses at 1 Hz both in control and in drug-treated preparations. Concerning the time courses of the difference between the Vmax values before and after drug treatments at the same diastolic interval, with increases in drug concentrations the intercepts at APD90 were increased but the time constants were not changed or slightly decreased in 8.1 to 5.4 mM [K+]0, whereas they were increased in 2.7 mM [K+]0. To understand the kinetic behavior of this drug on sodium channels, rate constants for the interaction of phenytoin with three states of channels in terms of Hondeghem-Katzung model were estimated from the above experiments of Vmax. The model most consistent with the present experiments was that with an affinity for inactivated channels 20 times greater than that for resting channels and with a minor affinity for open channels. Phenytoin produced a delay in the time course of recovery of overshoot and action potential duration at 0 mV (APD0), suggesting an additional inhibition of the slow channel by this drug.

  20. Visual Stimuli Evoked Action Potentials Trigger Rapidly Propagating Dendritic Calcium Transients in the Frog Optic Tectum Layer 6 Neurons.

    Directory of Open Access Journals (Sweden)

    Gytis Svirskis

    Full Text Available The superior colliculus in mammals or the optic tectum in amphibians is a major visual information processing center responsible for generation of orientating responses such as saccades in monkeys or prey catching avoidance behavior in frogs. The conserved structure function of the superior colliculus the optic tectum across distant species such as frogs, birds monkeys permits to draw rather general conclusions after studying a single species. We chose the frog optic tectum because we are able to perform whole-cell voltage-clamp recordings fluorescence imaging of tectal neurons while they respond to a visual stimulus. In the optic tectum of amphibians most visual information is processed by pear-shaped neurons possessing long dendritic branches, which receive the majority of synapses originating from the retinal ganglion cells. Since the first step of the retinal input integration is performed on these dendrites, it is important to know whether this integration is enhanced by active dendritic properties. We demonstrate that rapid calcium transients coinciding with the visual stimulus evoked action potentials in the somatic recordings can be readily detected up to the fine branches of these dendrites. These transients were blocked by calcium channel blockers nifedipine CdCl2 indicating that calcium entered dendrites via voltage-activated L-type calcium channels. The high speed of calcium transient propagation, >300 μm in <10 ms, is consistent with the notion that action potentials, actively propagating along dendrites, open voltage-gated L-type calcium channels causing rapid calcium concentration transients in the dendrites. We conclude that such activation by somatic action potentials of the dendritic voltage gated calcium channels in the close vicinity to the synapses formed by axons of the retinal ganglion cells may facilitate visual information processing in the principal neurons of the frog optic tectum.

  1. Barriers, facilitators, and potential strategies for increasing HPV vaccination: A statewide assessment to inform action.

    Science.gov (United States)

    Cartmell, Kathleen B; Young-Pierce, Jennifer; McGue, Shannon; Alberg, Anthony J; Luque, John S; Zubizarreta, Maria; Brandt, Heather M

    2017-12-07

    The objective was to investigate how state level strategies in South Carolina could maximize HPV vaccine uptake. An environmental scan identified barriers, facilitators, and strategies for improving HPV vaccination in South Carolina. Interviews were conducted with state leaders from relevant organizations such as public health agencies, medical associations, K-12 schools, universities, insurers, and cancer advocacy organizations. A thematic content analysis design was used. Digital interview files were transcribed, a data dictionary was created and data were coded using the data dictionary. Thirty four interviews were conducted with state leaders. Barriers to HPV vaccination included lack of HPV awareness, lack of provider recommendation, HPV vaccine concerns, lack of access and practice-level barriers. Facilitators included momentum for improving HPV vaccination, school-entry Tdap requirement, pharmacy-based HPV vaccination, state immunization registry, HEDIS measures and HPV vaccine funding. Strategies for improving HPV vaccination fell into three categories: 1) addressing lack of awareness about the importance of HPV vaccination among the public and providers; 2) advocating for policy changes around HPV vaccine coverage, vaccine education, and pharmacy-based vaccination; and 3) coordination of efforts. A statewide environmental scan generated a blueprint for action to be used to improve HPV vaccination in the state. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  2. Overexpression of the Large-Conductance, Ca2+-Activated K+ (BK) Channel Shortens Action Potential Duration in HL-1 Cardiomyocytes.

    Science.gov (United States)

    Stimers, Joseph R; Song, Li; Rusch, Nancy J; Rhee, Sung W

    2015-01-01

    Long QT syndrome is characterized by a prolongation of the interval between the Q wave and the T wave on the electrocardiogram. This abnormality reflects a prolongation of the ventricular action potential caused by a number of genetic mutations or a variety of drugs. Since effective treatments are unavailable, we explored the possibility of using cardiac expression of the large-conductance, Ca2+-activated K+ (BK) channel to shorten action potential duration (APD). We hypothesized that expression of the pore-forming α subunit of human BK channels (hBKα) in HL-1 cells would shorten action potential duration in this mouse atrial cell line. Expression of hBKα had minimal effects on expression levels of other ion channels with the exception of a small but significant reduction in Kv11.1. Patch-clamped hBKα expressing HL-1 cells exhibited an outward voltage- and Ca2+-sensitive K+ current, which was inhibited by the BK channel blocker iberiotoxin (100 nM). This BK current phenotype was not detected in untransfected HL-1 cells or in HL-1 null cells sham-transfected with an empty vector. Importantly, APD in hBKα-expressing HL-1 cells averaged 14.3 ± 2.8 ms (n = 10), which represented a 53% reduction in APD compared to HL-1 null cells lacking BKα expression. APD in the latter cells averaged 31.0 ± 5.1 ms (n = 13). The shortened APD in hBKα-expressing cells was restored to normal duration by 100 nM iberiotoxin, suggesting that a repolarizing K+ current attributed to BK channels accounted for action potential shortening. These findings provide initial proof-of-concept that the introduction of hBKα channels into a cardiac cell line can shorten APD, and raise the possibility that gene-based interventions to increase hBKα channels in cardiac cells may hold promise as a therapeutic strategy for long QT syndrome.

  3. Significant improvement in dynamic visual acuity after cataract surgery: a promising potential parameter for functional vision.

    Science.gov (United States)

    Ao, Mingxin; Li, Xuemin; Huang, Chen; Hou, Zhiqiang; Qiu, Weiqiang; Wang, Wei

    2014-01-01

    Dynamic visual acuity (DVA) is a relatively independent parameter for evaluating the ability to distinguish details of a moving target. The present study has been designed to discuss the extent to which age-related cataract impacts DVA in elderly individuals and to determine whether it could be restored after bilateral phacoemulsification combined with intraocular lens implantation surgery. Twenty-six elderly cataract patients scheduled for binocular cataract surgery and 30 elderly volunteers without cataract were enrolled in the study. DVA at 15, 30, 60 and 90 degree per second (dps) was assessed, and velocity-dependent visual acuity decreases between consecutive speed levels were calculated. Compared with the control group, the patient group exhibited significantly worse DVA performance at all speed levels (pDVA performance at every speed level in the patient group clearly improved (pDVA was more pronounced than the improvement in static visual acuity (p15 dps = 0.001 and pDVA was more severe than its effects on static visual acuity. After cataract surgery, not only static vision of the patients was restored markedly, but also the dynamic vision. DVA could be an important adjunct to the current evaluation system of functional vision, thereby meriting additional attention in clinical assessment.

  4. Tritium Plasma Experiment (TPE) - parameters and potentials for fusion plasma-wall interaction studies

    Energy Technology Data Exchange (ETDEWEB)

    Masashi Shimada; Robert D. Kolasinski; J. Phillip Sharpe; Rion A. Causey

    2011-08-01

    The Tritium plasma experiment (TPE) is a unique facility devoted to experiments on the behavior of deuterium/tritium in toxic (e.g. beryllium) and radioactive materials for fusion plasma-wall interaction (PWI) studies. A Langmuir probe was added to the system to characterize the plasma conditions in TPE. With this new diagnostic, we found the achievable electron temperature ranged from 5.0 to 10.0 eV, the electron density varied from 5.0 x 10{sup 16} to 2.5 x 10{sup 18} m{sup -3}, and the ion flux density varied between 5.0 x 10{sup 20} to 2.5 x 10{sup 22} m{sup -2}s{sup -1} along the centerline of the plasma. A comparison of these plasma parameters with the conditions expected for the plasma facing components (PFCs) in ITER shows that TPE is capable of achieving most (approximately 800 m{sup 2} of 850 m{sup 2} total PFCs area) of the expected ion flux density and electron density conditions.

  5. Whey protein potentiates the intestinotrophic action of glucagon-like peptide-2 in parenterally fed rats

    DEFF Research Database (Denmark)

    Liu, Xiaowen; Murali, Sangita G; Holst, Jens J

    2009-01-01

    protein component, casein, soy, or whey protein, potentiates the intestinal growth response to GLP-2 in rats with PN-induced mucosal hypoplasia. Rats received PN and continuous intravenous infusion of GLP-2 (100 microg/kg/day) for 7 days. Six EN groups received PN+GLP-2 for days 1-3 and partial PN+GLP-2...... plus EN for days 4-7. EN was provided by ad libitum intake of a semielemental liquid diet with different protein sources: casein, hydrolyzed soy, whey protein concentrate (WPC), and hydrolyzed WPC+casein. Controls received PN+GLP-2 alone. EN induced significantly greater jejunal sucrase activity...... whey protein, and not casein or soy, potentiated the ability of GLP-2 to reverse PN-induced mucosal hypoplasia and further increase ileal villus height, crypt depth, and mucosa cellularity compared with PN+GLP-2 alone, P whey protein to induce greater mucosal surface area...

  6. EFFECT OF NATURALLY OCCURRING XANTHINES ON BACTERIA. I. ANTIMICROBIAL ACTION AND POTENTIATING EFFECT ON ANTIBIOTIC SPECTRA.

    Science.gov (United States)

    RAJ, C V; DHALA, S

    1965-05-01

    The effect of xanthines on various microorganisms was studied. The antibacterial effect was not high; most of the test organisms could easily withstand a concentration of 2,500 mug/ml. Caffeine was more antibacterial than theophylline, and the latter more than theobromine. Caffeine citrate exhibited greater inhibitory effect than did pure caffeine. The effect was both bacteriostatic and bactericidal against susceptible organisms. The susceptibility of organisms to xanthines differed greatly even in related species. The morphology of Aerobacter aerogenes and A. cloacae was affected under the influence of caffeine; filamentation of cells followed sublethal doses. Potentiation was seen with antibiotics and caffeine; resistant strains were killed with a lower dose of drug in the presence of caffeine. This potentiating effect was pronounced with the tetracyclines; with streptomycin, the effect was the contrary.

  7. Optimization of potential field method parameters through networks for swarm cooperative manipulation tasks

    Directory of Open Access Journals (Sweden)

    Rocco Furferi

    2016-10-01

    Full Text Available An interesting current research field related to autonomous robots is mobile manipulation performed by cooperating robots (in terrestrial, aerial and underwater environments. Focusing on the underwater scenario, cooperative manipulation of Intervention-Autonomous Underwater Vehicles (I-AUVs is a complex and difficult application compared with the terrestrial or aerial ones because of many technical issues, such as underwater localization and limited communication. A decentralized approach for cooperative mobile manipulation of I-AUVs based on Artificial Neural Networks (ANNs is proposed in this article. This strategy exploits the potential field method; a multi-layer control structure is developed to manage the coordination of the swarm, the guidance and navigation of I-AUVs and the manipulation task. In the article, this new strategy has been implemented in the simulation environment, simulating the transportation of an object. This object is moved along a desired trajectory in an unknown environment and it is transported by four underwater mobile robots, each one provided with a seven-degrees-of-freedom robotic arm. The simulation results are optimized thanks to the ANNs used for the potentials tuning.

  8. Ruby laser-assisted depilation: The mode of action and potential ways of improved outcome

    Science.gov (United States)

    Topping, Adam Partington

    Aim - To improve efficacy and lessen side effects resulting from normal mode ruby laser (NMRL)-assisted depilation via a greater understanding of its mode of action and the development of novel methods of reducing associated epidermal damage. Employing a thermal imaging camera and ex vivo hair-bearing skin, the targets for the NMRL (pulse duration 900 musec and spot size 7 mm) were defined, the temperatures reached and the heat dissipation rates determined. Production of heat was confined to the hair follicles, with the peak temperatures reached varying considerably between hairs within the same treatment area and also between individuals. Histological assessment for a known indicator of cellular damage (p53 expression) identified the sites and extent of damage, which correlated with the peak temperatures measured. An energy meter was used to detect the penetration of NMRL light through ex vivo skin, which was found to be deeper than previously theorised. The black-haired mouse (C57B1/10) was assessed both macroscopically and histologically and found to be an acceptable animal model of NMRL depilation and associated epidermal damage. Attempts to reduce the epidermal damage by simply stopping the light reaching the epidermis using a chromophore block were assessed. Chromophore did indeed reduce the amount of epidermal damage detected in laser-irradiated ex vivo human skin, whereas in contrast it increased the wounding seen in the much thinner skin of the mouse. Nevertheless the mouse model showed that this technique did not affect the depilation efficacy. An alternative method of reducing epidermal damage using induction of the cells' intrinsic protective mechanisms (heat shock proteins, HSP) was assessed using cultured keratinocytes and the mouse model. Primarily, the sub-lethal temperature optimum for HSP expression in human keratinocytes was determined, then an in vitro model of NMRL-associated epidermal damage was established and the heat pre-treatment assessed

  9. An evaluation of the utility and limitations of counting motor unit action potentials in the surface electromyogram

    Science.gov (United States)

    Zhou, Ping; Zev Rymer, William

    2004-12-01

    The number of motor unit action potentials (MUAPs) appearing in the surface electromyogram (EMG) signal is directly related to motor unit recruitment and firing rates and therefore offers potentially valuable information about the level of activation of the motoneuron pool. In this paper, based on morphological features of the surface MUAPs, we try to estimate the number of MUAPs present in the surface EMG by counting the negative peaks in the signal. Several signal processing procedures are applied to the surface EMG to facilitate this peak counting process. The MUAP number estimation performance by this approach is first illustrated using the surface EMG simulations. Then, by evaluating the peak counting results from the EMG records detected by a very selective surface electrode, at different contraction levels of the first dorsal interosseous (FDI) muscles, the utility and limitations of such direct peak counts for MUAP number estimation in surface EMG are further explored.

  10. The effect of shoulder position on motor evoked and maximal muscle compound action potentials of the biceps brachii.

    Science.gov (United States)

    Collins, Brandon W; Button, Duane C

    2018-02-05

    The purpose of the study was to assess the effect of shoulder position, 0° versus 90° shoulder flexion, on stimulation intensity and maximal muscle compound action potentials (M max ) and motor evoked potentials (MEP) of the biceps brachii during both rest and 10% maximum voluntary contraction (MVC). Nine participants completed two experimental sessions with four conditions. During each condition, transcranial magnetic (TMS) and Erb's point stimulation were used to elicit MEPs and M max , respectively. During rest, the TMS intensity to elicit a MEP response (pshoulder-position and state-dependent, whereas MEP and M max amplitudes were only shoulder position-dependent. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Significant improvement in dynamic visual acuity after cataract surgery: a promising potential parameter for functional vision.

    Directory of Open Access Journals (Sweden)

    Mingxin Ao

    Full Text Available PURPOSE: Dynamic visual acuity (DVA is a relatively independent parameter for evaluating the ability to distinguish details of a moving target. The present study has been designed to discuss the extent to which age-related cataract impacts DVA in elderly individuals and to determine whether it could be restored after bilateral phacoemulsification combined with intraocular lens implantation surgery. METHODS: Twenty-six elderly cataract patients scheduled for binocular cataract surgery and 30 elderly volunteers without cataract were enrolled in the study. DVA at 15, 30, 60 and 90 degree per second (dps was assessed, and velocity-dependent visual acuity decreases between consecutive speed levels were calculated. RESULTS: Compared with the control group, the patient group exhibited significantly worse DVA performance at all speed levels (p<0.001, and the decreases in velocity-dependent visual acuity were more serious in the patient group at the intervals of 0-15 dps (p<0.001, 15-30 dps (p = 0.007 and 30-60 dps (p = 0.008. Postoperatively, DVA performance at every speed level in the patient group clearly improved (p<0.001 and recovered to levels compatible to the control group. The decrease in visual acuity with increasing speed was less pronounced than during the preoperative phase (p0-15 dps = 0.001, p15-30 dps<0.001 and p30-60 dps = 0.001 and became similar to that of the control group. The postoperative visual benefit regarding DVA was more pronounced than the improvement in static visual acuity (p15 dps = 0.001 and p<0.001 at 30 dps, 60 dps and 90 dps. CONCLUSIONS: The impact of age-related cataract on DVA was more severe than its effects on static visual acuity. After cataract surgery, not only static vision of the patients was restored markedly, but also the dynamic vision. DVA could be an important adjunct to the current evaluation system of functional vision, thereby meriting additional attention in clinical assessment.

  12. Sensitivity of Rabbit Ventricular Action Potential and Ca2+ Dynamics to Small Variations in Membrane Currents and Ion Diffusion Coefficients

    Directory of Open Access Journals (Sweden)

    Yuan Hung Lo

    2013-01-01

    Full Text Available Little is known about how small variations in ionic currents and Ca2+ and Na+ diffusion coefficients impact action potential and Ca2+ dynamics in rabbit ventricular myocytes. We applied sensitivity analysis to quantify the sensitivity of Shannon et al. model (Biophys. J., 2004 to 5%–10% changes in currents conductance, channels distribution, and ion diffusion in rabbit ventricular cells. We found that action potential duration and Ca2+ peaks are highly sensitive to 10% increase in L-type Ca2+ current; moderately influenced by 10% increase in Na+-Ca2+ exchanger, Na+-K+ pump, rapid delayed and slow transient outward K+ currents, and Cl− background current; insensitive to 10% increases in all other ionic currents and sarcoplasmic reticulum Ca2+ fluxes. Cell electrical activity is strongly affected by 5% shift of L-type Ca2+ channels and Na+-Ca2+ exchanger in between junctional and submembrane spaces while Ca2+-activated Cl−-channel redistribution has the modest effect. Small changes in submembrane and cytosolic diffusion coefficients for Ca2+, but not in Na+ transfer, may alter notably myocyte contraction. Our studies highlight the need for more precise measurements and further extending and testing of the Shannon et al. model. Our results demonstrate usefulness of sensitivity analysis to identify specific knowledge gaps and controversies related to ventricular cell electrophysiology and Ca2+ signaling.

  13. Endocannabinoids produced upon action potential firing evoke a Cl(-) current via type-2 cannabinoid receptors in the medial prefrontal cortex.

    Science.gov (United States)

    den Boon, Femke S; Chameau, Pascal; Houthuijs, Kas; Bolijn, Simone; Mastrangelo, Nicolina; Kruse, Chris G; Maccarrone, Mauro; Wadman, Wytse J; Werkman, Taco R

    2014-12-01

    The functional presence of type-2 cannabinoid receptors (CB2Rs) in layer II/III pyramidal neurons of the rat medial prefrontal cortex (mPFC) was recently demonstrated. In the present study, we show that the application of the endocannabinoids (eCBs) 2-arachidonoylglycerol (2-AG) and methanandamide [a stable analog of the eCB anandamide (AEA)] can activate CB2Rs of mPFC layer II/III pyramidal neurons, which subsequently induces a Cl(-) current. In addition, we show that action potential (AP) firing evoked by 20-Hz current injections results in an eCB-mediated opening of Cl(-) channels via CB2R activation. This AP-evoked synthesis of eCBs is dependent on the Ca(2+) influx through N-type voltage-gated calcium channels. Our results indicate that 2-AG is the main eCB involved in this process. Finally, we demonstrate that under physiologically relevant intracellular Cl(-) conditions, 20-Hz AP firing leads to a CB2R-dependent reduction in neuronal excitability. Altogether, our data indicate that eCBs released upon action potential firing can modulate, through CB2R activation, neuronal activity in the mPFC. We discuss how this may be a mechanism to prevent excessive neuronal firing.

  14. Intraoperative observation of changes in cochlear nerve action potentials during exposure to electromagnetic fields generated by mobile phones.

    Science.gov (United States)

    Colletti, Vittorio; Mandalà, Marco; Manganotti, Paolo; Ramat, Stefano; Sacchetto, Luca; Colletti, Liliana

    2011-07-01

    The rapid spread of devices generating electromagnetic fields (EMF) has raised concerns as to the possible effects of this technology on humans. The auditory system is the neural organ most frequently and directly exposed to electromagnetic activity owing to the daily use of mobile phones. In recent publications, a possible correlation between mobile phone usage and central nervous system tumours has been detected. Very recently a deterioration in otoacoustic emissions and in the auditory middle latency responses after intensive and long-term magnetic field exposure in humans has been demonstrated. To determine with objective observations if exposure to mobile phone EMF affects acoustically evoked cochlear nerve compound action potentials, seven patients suffering from Ménière's disease and undergoing retrosigmoid vestibular neurectomy were exposed to the effects of mobile phone placed over the craniotomy for 5 min. All patients showed a substantial decrease in amplitude and a significant increase in latency of cochlear nerve compound action potentials during the 5 min of exposure to EMF. These changes lasted for a period of around 5 min after exposure. The possibility that EMF can produce relatively long-lasting effects on cochlear nerve conduction is discussed and analysed in light of contrasting previous literature obtained under non-surgical conditions. Limitations of this novel approach, including the effects of the anaesthetics, craniotomy and surgical procedure, are presented in detail.

  15. The distribution and propagation pattern of motor unit action potentials studied by multi-channel surface EMG.

    Science.gov (United States)

    Yamada, M; Kumagai, K; Uchiyama, A

    1987-11-01

    We developed the multi-channel surface EMG system using a matrix-type of surface electrode and with the aid of digital signal processing. The subjects were 14 normals (4-50 years) and 2 patients with Duchenne muscular dystrophy (7 and 8 years). The biceps brachii and the tibialis anterior muscles were investigated. The location of the motor end-plates and the measurement of muscle fiber conduction velocity were evaluated by the time shift of bipolar EMG arrays along muscle fibers, or by the distribution map of averaged motor unit action potentials (MUAPs). The lateral extension of a motor unit could be also estimated from the changes of averaged MUAP's amplitudes in the distribution map. Moreover in the biceps of 2 patients with Duchenne dystrophy, the mean muscle fiber conduction velocities were reduced compared to normal subjects, and characteristic propagation patterns of action potentials were obtained. In the 2-dimensional or 3-dimensional distribution map of integrated monopolar EMGs, the high density area agreed with the motor end-plate band.

  16. Sodium entry during action potentials of mammalian neurons: incomplete inactivation and reduced metabolic efficiency in fast-spiking neurons.

    Science.gov (United States)

    Carter, Brett C; Bean, Bruce P

    2009-12-24

    We measured the time course of sodium entry during action potentials of mouse central neurons at 37 degrees C to examine how efficiently sodium entry is coupled to depolarization. In cortical pyramidal neurons, sodium entry was nearly completely confined to the rising phase of the spike: only approximately 25% more sodium enters than the theoretical minimum necessary for spike depolarization. However, in fast-spiking GABAergic neurons (cerebellar Purkinje cells and cortical interneurons), twice as much sodium enters as the theoretical minimum. The extra entry occurs because sodium channel inactivation is incomplete during the falling phase of the spike. The efficiency of sodium entry in different cell types is primarily a function of action potential shape and not cell-type-specific differences in sodium channel kinetics. The narrow spikes of fast-spiking GABAergic neurons result in incomplete inactivation of sodium channels; this reduces metabolic efficiency but likely enhances the ability to fire spikes at high frequency. 2009 Elsevier Inc. All rights reserved.

  17. Period doubling cascades of limit cycles in cardiac action potential models as precursors to chaotic early Afterdepolarizations.

    Science.gov (United States)

    Kügler, Philipp; Bulelzai, M A K; Erhardt, André H

    2017-04-04

    Early afterdepolarizations (EADs) are pathological voltage oscillations during the repolarization phase of cardiac action potentials (APs). EADs are caused by drugs, oxidative stress or ion channel disease, and they are considered as potential precursors to cardiac arrhythmias in recent attempts to redefine the cardiac drug safety paradigm. The irregular behaviour of EADs observed in experiments has been previously attributed to chaotic EAD dynamics under periodic pacing, made possible by a homoclinic bifurcation in the fast subsystem of the deterministic AP system of differential equations. In this article we demonstrate that a homoclinic bifurcation in the fast subsystem of the action potential model is neither a necessary nor a sufficient condition for the genesis of chaotic EADs. We rather argue that a cascade of period doubling (PD) bifurcations of limit cycles in the full AP system paves the way to chaotic EAD dynamics across a variety of models including a) periodically paced and spontaneously active cardiomyocytes, b) periodically paced and non-active cardiomyocytes as well as c) unpaced and spontaneously active cardiomyocytes. Furthermore, our bifurcation analysis reveals that chaotic EAD dynamics may coexist in a stable manner with fully regular AP dynamics, where only the initial conditions decide which type of dynamics is displayed. EADs are a potential source of cardiac arrhythmias and hence are of relevance both from the viewpoint of drug cardiotoxicity testing and the treatment of cardiomyopathies. The model-independent association of chaotic EADs with period doubling cascades of limit cycles introduced in this article opens novel opportunities to study chaotic EADs by means of bifurcation control theory and inverse bifurcation analysis. Furthermore, our results may shed new light on the synchronization and propagation of chaotic EADs in homogeneous and heterogeneous multicellular and cardiac tissue preparations.

  18. Color atomic force microscopy: A method to acquire three independent potential parameters to generate a color image

    Science.gov (United States)

    Allain, P. E.; Damiron, D.; Miyazaki, Y.; Kaminishi, K.; Pop, F. V.; Kobayashi, D.; Sasaki, N.; Kawakatsu, H.

    2017-09-01

    Atomic force microscopy has enabled imaging at the sub-molecular level, and 3D mapping of the tip-surface potential field. However, fast identification of the surface still remains a challenging topic for the microscope to enjoy widespread use as a tool with chemical contrast. In this paper, as a step towards implementation of such function, we introduce a control scheme and mathematical treatment of the acquired data that enable retrieval of essential information characterizing this potential field, leading to fast acquisition of images with chemical contrast. The control scheme is based on the tip sample distance modulation at an angular frequency ω , and null-control of the ω component of the measured self-excitation frequency of the oscillator. It is demonstrated that this control is robust, and that effective Morse Parameters that give satisfactory curve fit to the measured frequency shift can be calculated at rates comparable to the scan. Atomic features with similar topography were distinguished by differences in these parameters. The decay length parameter was resolved with a resolution of 10 pm. The method was demonstrated on quenched silicon at a scan rate comparable to conventional imaging.

  19. A change in the parameters of P300 evoked potentials in relation to the degree of exacerbation of pain syndrome

    Directory of Open Access Journals (Sweden)

    A P Rachin

    2012-01-01

    Full Text Available In chronic pain, the state of suprasegmental brain structures (the cortex, limbic system, truncodiencephalic structures, which form the motivational-affective and cognitive components of pain behavior, actively affects pain afferentation as well. The purpose of the study was to comparatively analyze the parameters and topographic distribution of P300 cognitive evoked potential in patients with lower back pain. Sixty patients aged 22 to 60 years were examined. The authors made their clinical and neurological examinations, collected medical history data, and assessed back pain intensity by a visual analog scale. The findings were compared with the parameters of cognitive evoked potentials (the separating of P300 to count; keystroke in the recognition of significant stimuli; elaboration of a verbal and nonverbal visual stimulation protocol, by using emotionally significant stimuli. The processes of recognition and differentiation, those of directed attention, and the rate of information processing slowed down in patients with different stages of pain syndrome. The P300 separating procedure using the emotionally significant stimuli allows one to assess the specific features of chronization of pain syndromes and the presence of pain memory in the central nervous system of such patients. The estimation of P300 parameters over time or during treatment are of particular value for the optimization and evaluation of its efficiency.

  20. Effect of water quality and operational parameters on trihalomethanes formation potential in Dez River water, Iran

    Directory of Open Access Journals (Sweden)

    Bahman Ramavandi

    2015-09-01

    Full Text Available This study assesses the influence of the total organic carbon (TOC content, chlorine quantity, water temperature, bromide ion concentration, and seasonal variations on trihalomethanes (THMs formation potential (THMFP in Dez River water in Iran. The water temperature and TOC content had a significant effect on THMFP. Further, the experimental results showed that increasing the concentration of bromide ions enhances the formation of dibromochloromethane and bromoform. It was found that the THMFP in Dez River water during summer times was relatively higher than 100 µg/L, maximum contaminant level for THMs in drinking water. By increasing the reaction time until 80 h, the THMFP was gradually increased and reached to 177.4 µg/L. The most abundant fraction of natural organic matter in the river was hydrophobic acid fraction (49.4 μg/L. Overall, our study demonstrated that however the THMFP of Dez River water was relatively high but a usual waterworks could effectively reduce THMFP.

  1. Exploring potential mechanisms of action of natalizumab in secondary progressive multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, Finn; Cadavid, Diego; Steiner, Deborah

    2016-01-01

    Multiple sclerosis (MS) is a common and chronic central nervous system (CNS) demyelinating disease and a leading cause of permanent disability. Patients most often present with a relapsing-remitting disease course, typically progressing over time to a phase of relentless advancement in secondary...... progressive MS (SPMS), for which approved disease-modifying therapies are limited. In this review, we summarize the pathophysiological mechanisms involved in the development of SPMS and the rationale and clinical potential for natalizumab, which is currently approved for the treatment of relapsing forms of MS...... in brain lesions and brain atrophy as well as beneficial effects on clinical measures, such as reduced frequency and severity of relapse and reduced accumulation of disability. Natalizumab treatment also reduces levels of cerebrospinal fluid chemokines and other biomarkers of intrathecal inflammation...

  2. Assessment of process control parameters in the biochemical methane potential of sunflower oil cake

    Energy Technology Data Exchange (ETDEWEB)

    Raposo, F.; Borja, R.; Rincon, B. [Instituto de la Grasa (CSIC), Avda. Padre Garcia Tejero 4, 41012 Seville (Spain); Jimenez, A.M. [Departamento de Ciencias Ambientales, Universidad Pablo de Olavide, Ctra. De Utrera, km 1, 41013 Sevilla (Spain)

    2008-12-15

    A laboratory-scale study was conducted on the batch anaerobic digestion of sunflower oil cake (SuOC), solid waste derived from the extraction process of sunflower oil. A multi-reactor system was used to compare methane production from this waste at inoculum to substrate ratios (ISRs) of 3.0, 2.0, 1.5, 1.0, 0.8 and 0.5 (expressed as volatile solids (VS) basis). The tests were carried out at mesophilic temperature (35 C) and run against a control of inoculum without substrate. The results obtained in the biochemical methane potential (BMP) tests showed that the ultimate methane yield (Y{sub M,ult}) decreased considerably from 227{+-}23 to 107{+-}11 ml CH{sub 4} at standard temperature and pressure (STP) conditions g{sup -1} VS{sub added} when the ISR decreased from 3.0 to 0.5, showing a clear influence of the ISR on the methane yield coefficient. The biodegradability (BD) of the waste also decreased from 86% to 41% when the ISR varied from 3.0 to 0.5. A net total ammonia nitrogen (TAN) yield of 39.2 mg N g{sup -1} VS{sub added} was obtained, and this value was not influenced by the ISRs assayed, which demonstrated the appropriate operation of the hydrolytic-acidogenic stage of the overall digestion process. A clear imbalance of the methanogenic process was observed at the lowest ISRs studied (0.5 and 0.8) due to a considerable increase in CODs and TVFA in the digestates. The profile of VFA was also influenced by the ISR, typical of the proteinaceous substrates. (author)

  3. Quantitative motor unit action potential analysis of supraspinatus, infraspinatus, deltoideus and biceps femoris muscles in adult Royal Dutch sport horses.

    Science.gov (United States)

    Jose-Cunilleras, E; Wijnberg, I D

    2016-03-01

    Reference values for quantitative electromyography (QEMG) in shoulder and hindlimb muscles of horses are limited. To determine normative data on QEMG analysis of supraspinatus (SS), infraspinatus (IS), deltoideus (DT) and biceps femoris (BF) muscles. Experimental observational study and retrospective case series. Seven adult healthy Royal Dutch sport horses underwent quantitative motor unit action potential analysis of each muscle using commercial electromyography equipment. Measurements were made according to published methods. One-way ANOVA was used to compare quantitative motor unit action potential variables between muscles, with post hoc testing according to Bonferroni, with significance set at Paction potential were 8.7-10.4 ms, 651-867 μV, 3.2-3.7, 3.7-4.7, 1054-1457 μV·ms and 1.1-1.5 for SS, 9.6-11.0 ms, 779-1082 μV, 3.3-3.7, 3.8-4.7, 1349-2204 μV·ms and 1.4-1.9 for IS, 6.0-9.1 ms, 370-691 μV, 2.9-3.7, 2.8-4.5, 380-1374 μV·ms and 0.3-1.3 for DT and 5.7-7.8 ms, 265-385 μV, 2.7-3.2, 2.6-3.1, 296-484 μV·ms and 0.2-0.5 for BF, respectively. Mean duration, amplitude, number of phases and turns, area and size index were significantly (P15% polyphasic motor unit action potentials in SS and IS muscles. Differences between muscles should be taken into account when performing QEMG in order to be able to distinguish normal horses from horses with suspected neurogenic or myogenic disorders. These normal data provide the basis for objective QEMG assessment of shoulder and hindlimb muscles. Quantitative electromyography appears to be helpful in diagnosing neuropathies and discriminating these from myopathies. © 2015 EVJ Ltd.

  4. Genetic parameters for predicted methane production and potential for reducing enteric emissions through genomic selection.

    Science.gov (United States)

    Haas, Y de; Windig, J J; Calus, M P L; Dijkstra, J; Haan, M de; Bannink, A; Veerkamp, R F

    2011-12-01

    Mitigation of enteric methane (CH₄) emission in ruminants has become an important area of research because accumulation of CH₄ is linked to global warming. Nutritional and microbial opportunities to reduce CH₄ emissions have been extensively researched, but little is known about using natural variation to breed animals with lower CH₄ yield. Measuring CH₄ emission rates directly from animals is difficult and hinders direct selection on reduced CH₄ emission. However, improvements can be made through selection on associated traits (e.g., residual feed intake, RFI) or through selection on CH₄ predicted from feed intake and diet composition. The objective was to establish phenotypic and genetic variation in predicted CH₄ output, and to determine the potential of genetics to reduce methane emissions in dairy cattle. Experimental data were used and records on daily feed intake, weekly body weights, and weekly milk production were available from 548 heifers. Residual feed intake (MJ/d) is the difference between net energy intake and calculated net energy requirements for maintenance as a function of body weight and for fat- and protein-corrected milk production. Predicted methane emission (PME; g/d) is 6% of gross energy intake (Intergovernmental Panel on Climate Change methodology) corrected for energy content of methane (55.65 kJ/g). The estimated heritabilities for PME and RFI were 0.35 and 0.40, respectively. The positive genetic correlation between RFI and PME indicated that cows with lower RFI have lower PME (estimates ranging from 0.18 to 0.84). Hence, it is possible to decrease the methane production of a cow by selecting more-efficient cows, and the genetic variation suggests that reductions in the order of 11 to 26% in 10 yr are theoretically possible, and could be even higher in a genomic selection program. However, several uncertainties are discussed; for example, the lack of true methane measurements (and the key assumption that methane

  5. Covalent NEDD8 conjugation increases RCAN1 protein stability and potentiates its inhibitory action on calcineurin.

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    Eun Hye Noh

    Full Text Available Similar to ubiquitin, regulatory roles for NEDD8 (neural precursor cell-expressed developmentally down-regulated 8 are being clarified during cell growth, signal transduction, immune response, and development. However, NEDD8 targets and their functional alterations are not well known. Regulator of calcineurin 1 (RCAN1/DSCR1P1 is located near the Down syndrome critical region on the distal part of chromosome 21, and its gene product is an endogenous inhibitor of calcineurin signaling. RCAN1 is modified by ubiquitin and consequently undergoes proteasomal degradation. Here we report that NEDD8 is conjugated to RCAN1 (RCAN1-1S via three lysine residues, K96, K104, and K107. Neddylation enhances RCAN1 protein stability without affecting its cellular location. In addition, we found that neddylation significantly inhibits proteasomal degradation of RCAN1, which may underlie the ability of NEDD8 to enhance RCAN1 stability. Furthermore, neddylation increases RCAN1 binding to calcineurin, which potentiates its inhibitory activity toward downstream NFAT signaling. The present study provides a new regulatory mechanism of RCAN1 function and highlights an important role for diverse RCAN1-involved cellular physiology.

  6. Covalent NEDD8 conjugation increases RCAN1 protein stability and potentiates its inhibitory action on calcineurin.

    Science.gov (United States)

    Noh, Eun Hye; Hwang, Hee Sook; Hwang, Hee Sun; Min, Boram; Im, Eunju; Chung, Kwang Chul

    2012-01-01

    Similar to ubiquitin, regulatory roles for NEDD8 (neural precursor cell-expressed developmentally down-regulated 8) are being clarified during cell growth, signal transduction, immune response, and development. However, NEDD8 targets and their functional alterations are not well known. Regulator of calcineurin 1 (RCAN1/DSCR1P1) is located near the Down syndrome critical region on the distal part of chromosome 21, and its gene product is an endogenous inhibitor of calcineurin signaling. RCAN1 is modified by ubiquitin and consequently undergoes proteasomal degradation. Here we report that NEDD8 is conjugated to RCAN1 (RCAN1-1S) via three lysine residues, K96, K104, and K107. Neddylation enhances RCAN1 protein stability without affecting its cellular location. In addition, we found that neddylation significantly inhibits proteasomal degradation of RCAN1, which may underlie the ability of NEDD8 to enhance RCAN1 stability. Furthermore, neddylation increases RCAN1 binding to calcineurin, which potentiates its inhibitory activity toward downstream NFAT signaling. The present study provides a new regulatory mechanism of RCAN1 function and highlights an important role for diverse RCAN1-involved cellular physiology.

  7. Phytochemistry and potential therapeutic actions of Boswellic acids: A mini-review

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    Farah Iram

    2017-06-01

    Full Text Available The pentacyclic triterpenic acids isolated from the oleo gum resin of various Boswellia species are collectively called as Boswellic acids (BA. The oleo gum resin obtained from Indian variety i.e. Boswellia serrata (Family – Burseraceae is commonly known as Salai guggal. The resin fraction of Salai guggal is rich in Boswellic acids and its essential oil is composed of a mixture of mono, di and sesquiterpenes while gum fraction chiefly contains pentose and hexose sugars. This oleo-gum resin is quite popular among traditional practitioners of traditional Chinese and Indian Systems of medicine owing to their wide range of useful biological properties such as anti-inflammatory, anti-arthritic, anti-rheumatic, anti-diarrheal, anti-hyperlipidemic, anti-asthmatic, anti-cancer, anti-microbial anti-fungal, anti-complementary and analgesic activity, etc. It has been used as a herbal medicine since the prehistoric time to cure acute and chronic ailments including inflammatory diseases. Phytochemical investigation of this herbal medicine lead to identification of Boswellic acids which are found to be novel, potent, specific anti-inflammatory agents due to non-redox inhibition of 5-lipoxygenase (5-LO enzyme. However, the other important targets of Boswellic acids also include topoisomerases, angiogenesis, and cytochrome p450 enzymes. This review is a sincere attempt to discuss and present the current status of therapeutic potential, phytochemical as well as pharmacological profile of Boswellic acids primarily obtained from B. serrata.

  8. Control of Postharvest Bacterial Soft Rot by Gamma Irradiation and its Potential Modes of Action

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    Rae-Dong Jeong

    2016-04-01

    Full Text Available Gamma irradiation was evaluated for its in vitro and in vivo antibacterial activity against a postharvest bacterial pathogen, Erwinia carotovora subsp. carotovora (Ecc. Gamma irradiation in a bacteria cell suspension resulted in a dramatic reduction of the viable counts as well as an increase in the amounts of DNA and protein released from the cells. Gamma irradiation showed complete inactivation of Ecc, especially at a dose of 0.6 kGy. In addition, scanning electron microscopy of irradiated cells revealed severe damage on the surface of most bacterial cells. Along with the morphological changes of cells by gamma irradiation, it also affected the membrane integrity in a dose-dependent manner. The mechanisms by which the gamma irradiation decreased the bacterial soft rot can be directly associated with the disruption of the cell membrane of the bacterial pathogen, along with DNA fragmentation, results in dose-dependent cell inactivation. These findings suggest that gamma irradiation has potential as an antibacterial approach to reduce the severity of the soft rot of paprika.

  9. Menthol-induced action potentials in Conocephalum conicum as a result of unspecific interactions between menthol and the lipid phase of the plasma membrane.

    Science.gov (United States)

    Kupisz, Kamila; Trebacz, Kazimierz; Gruszecki, Wiesław I

    2015-07-01

    Our previous study has shown that the liverwort Conocephalum conicum generates action potentials (APs) in response to both temperature drop and menthol, which are also activators of the TRPM8 (transient receptor potential melastatin 8) receptor in animals. Not only similarities but also differences between electrical reactions to menthol and cooling observed in the liverwort aroused our interest in the action of menthol at the molecular level. Patch-clamp investigations have shown that menthol causes a reduction of current flowing through slow vacuolar (SV) channels to 29 ± 10% of the initial value (n = 9); simultaneously, it does not influence magnitudes of currents passing through a single SV channel. This may point to an unspecific interaction between menthol and the lipid phase of the membrane. An influence of menthol on lipid organization in membranes was investigated in two-component monomolecular layers formed with menthol and dipalmitoylphosphatidylcholine (DPPC) at the argon-water interface. Analyses of the mean molecular area parameters vs the molar fraction of the menthol component have shown over-additivity (approximately 20 Å(2) ) in the region of high molar fractions of menthol. Infrared absorption spectroscopy studies have shown that menthol, most probably, induces breaking of a hydrogen bond network formed by ester carbonyl groups and water bridges in the lipid membrane and binds to the polar head group region of DPPC. We conclude that the disruption in the lipid phase of the membrane influences ion channels and/or pumps and subsequently causes generation of APs in excitable plants such as C. conicum. © 2014 Scandinavian Plant Physiology Society.

  10. Effects of tocainide and lidocaine on the transmembrane action potentials as related to external potassium and calcium concentrations in guinea-pig papillary muscles.

    Science.gov (United States)

    Oshita, S; Sada, H; Kojima, M; Ban, T

    1980-10-01

    Effects of lidocaine and tocainide on transmembrane potentials were studied in isolated guinea-pig papillary muscles, superfused with modified Tyrode's solution containing either 5.4, 2.7, 10.0 or 8.1 mmol/l potassium concentration, [K]0. The last solution applied contained either 1.8 (normal [Ca]0) or 7.2 mmol/l [Ca]0 (high [Ca]0. The concentrations of lidocaine and tocainide used were 18.5, 36.9 and 73.9 mumol/l and 43.7, 87.5 and 174.9 mumol/l in 5.4 mmol/l [K]0 solution and 36.9 and 87.5 mumol/l in the other solutions, respectively. At the driving rate of 1 Hz in 5.4 mmol/l "K]0 solution, both drugs produced dose-dependently a reduction of maximum rate of rise of action potential (Vmax), together with a prolongation of the relative refractory period. Vmax decreased progressively as the driving rate was increased from 1 Hz (for lidocaine) and from 0.25 Hz (for tocainide) to 5 Hz. This action was accentuated dose-dependently. A slow component (time constant tau = 232 ms for lidocaine, 281--303 ms for tocainide) and slower component (tau = 2.1--3.8 s for tocainide) of the recovery (reactivation) of Vmax were observed in premature responses at 0.25 Hz and in the first response after interruption of the basic driving rate at 1 Hz. All these effects were accentuated with rising [K]0 and attenuated in the high [Ca]0 solution. Both drugs abbreviated the action potential duration at 50% (APD50) and 90% (APD90) levels at 5.4, 8.1 and 10.0 mmol/l [K]0 but not at 2.7 mmol/l [K]0 nor a high [Ca]0 at 1 Hz. These [K]0-dependent effects of lidocaine on Vmax were successfully simulated by the model proposed by Hondeghem and Katzung (1977), with a slight change in parameter values. The mode of interaction of lidocaine with sodium channels in the open, closed and rested states was deduced from these results.

  11. RESEARCHES REGARDING THE CHANGES OF SOME PHYSIOLOGICAL PARAMETERS AT THE PRUSSIAN CARP (Carassius auratus gibelio Bloch 1782 UNDER THE ACTION OF THE DUAL GOLD 960 EC HERBICIDE

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    Elena Diana Biţu

    2016-12-01

    Full Text Available Herbicides are chemical substances with selective toxic action (limited for some vegetal species or general (for any species, used to fight against weeds in the crops, fruit and grapes-growing fields, parks etc. The administration of herbicides though has complex effects on the biocenosis. In the aquatic environment, they have proved to be toxic not only for the aimed plants, but also for numerous species of animals. The deterioration of the aquatic environment is accentuated by the fact that plants that had died due to the treatment decompose themselves in a rapid manner, leading to the decrease of the oxygen level in the water, the final consequence being the increase in the death rate of the animals. This paper has studied the action of the Dual Gold 960 EC herbicide in different concentrations on some physiological indicators for the Prussian carp (Carassiusauratusgibelio Bloch 1782. The herbicide has had an inhibitive effect on the researched parameters for all the used concentrations.

  12. Simulations of the cardiac action potential based on the Hodgkin-Huxley kinetics with the use of Microsoft Excel spreadsheets.

    Science.gov (United States)

    Wu, Sheng-Nan

    2004-03-31

    The purpose of this study was to develop a method to simulate the cardiac action potential using a Microsoft Excel spreadsheet. The mathematical model contained voltage-gated ionic currents that were modeled using either Beeler-Reuter (B-R) or Luo-Rudy (L-R) phase 1 kinetics. The simulation protocol involves the use of in-cell formulas directly typed into a spreadsheet. The capability of spreadsheet iteration was used in these simulations. It does not require any prior knowledge of computer programming, although the use of the macro language can speed up the calculation. The normal configuration of the cardiac ventricular action potential can be well simulated in the B-R model that is defined by four individual ionic currents, each representing the diffusion of ions through channels in the membrane. The contribution of Na+ inward current to the rate of depolarization is reproduced in this model. After removal of Na+ current from the model, a constant current stimulus elicits an oscillatory change in membrane potential. In the L-R phase 1 model where six types of ionic currents were defined, the effect of extracellular K+ concentration on changes both in the time course of repolarization and in the time-independent K+ current can be demonstrated, when the solutions are implemented in Excel. Using the simulation protocols described here, the users can readily study and graphically display the underlying properties of ionic currents to see how changes in these properties determine the behavior of the heart cell. The method employed in these simulation protocols may also be extended or modified to other biological simulation programs.

  13. TAK1 inhibition subverts the osteoclastogenic action of TRAIL while potentiating its antimyeloma effects.

    Science.gov (United States)

    Tenshin, Hirofumi; Teramachi, Jumpei; Oda, Asuka; Amachi, Ryota; Hiasa, Masahiro; Bat-Erdene, Ariunzaya; Watanabe, Keiichiro; Iwasa, Masami; Harada, Takeshi; Fujii, Shiro; Kagawa, Kumiko; Sogabe, Kimiko; Nakamura, Shingen; Miki, Hirokazu; Kurahashi, Kiyoe; Yoshida, Sumiko; Aihara, Kenichi; Endo, Itsuro; Tanaka, Eiji; Matsumoto, Toshio; Abe, Masahiro

    2017-11-14

    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) agonists induce tumor-specific apoptosis indicating that they may be an attractive therapeutic strategy against cancers, including multiple myeloma (MM). Osteoclastogenesis is highly induced in MM, which in turn enhances MM growth, thereby forming a vicious cycle between MM tumor expansion and bone destruction. However, the effects of TRAIL on MM-enhanced osteoclastogenesis remain largely unknown. Here, we show that TRAIL induced apoptosis in MM cells, but not in osteoclasts (OCs), and that it rather facilitated receptor activator of NF-κB ligand-induced osteoclastogenesis along with upregulation of cellular FLICE inhibitory protein (c-FLIP). TRAIL did not induce death-inducing signaling complex formation in OCs, but formed secondary complex (complex II) with the phosphorylation of transforming growth factor β-activated kinase-1 (TAK1), and thus activated NF-κB signaling. c-FLIP knockdown abolished complex II formation, thus permitting TRAIL induction of OC cell death. The TAK1 inhibitor LLZ1640-2 abrogated the TRAIL-induced c-FLIP upregulation and NF-κB activation, and triggered TRAIL-induced caspase-8 activation and cell death in OCs. Interestingly, the TRAIL-induced caspase-8 activation caused enzymatic degradation of the transcription factor Sp1 to noticeably reduce c-FLIP expression, which further sensitized OCs to TRAIL-induced apoptosis. Furthermore, the TAK1 inhibition induced antiosteoclastogenic activity by TRAIL even in cocultures with MM cells while potentiating TRAIL's anti-MM effects. These results demonstrated that osteoclastic lineage cells use TRAIL for their differentiation and activation through tilting caspase-8-dependent apoptosis toward NF-κB activation, and that TAK1 inhibition subverts TRAIL-mediated NF-κB activation to resume TRAIL-induced apoptosis in OCs while further enhancing MM cell death in combination with TRAIL.

  14. Potassium conductances mediate bidirectional state-dependent modulation of action potential evoked dendritic calcium signals in dentate gyrus granule cells

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    János Brunner

    2014-03-01

    Full Text Available Backpropagating action potentials (bAPs and local calcium signals that they trigger are fundamental for dendritic functions. Here we addressed the question what extent the changes of local dendritic membrane properties can contribute to the shaping of the coupling between dendritic action potentials and the local calcium responses. Using a combination of in vitro electrophysiological and confocal imaging techniques we found that activation of dendritic GIRK channels via mGlu2 or GABAB receptors enhanced the bAP¬-triggered calcium signals in the dendrites of dentate gyrus granule cells (GCs. The enhancement of calcium signals was significant only in those dendritic regions, where these receptors are predominantly expressed. Similarly to GIRK channel activation, somatic hyperpolarization by DC current injection (from -64 mV to -77 mV, significantly increased bAP-associated calcium signals in the proximal dendrites. The hyperpolarization was associated with a decrease in the input resistance due to the rectification of the membrane potential of GCs. The effect of hyperpolarization on the calcium signals was maintained when T-type calcium currents were blocked but it decreased when GIRK channels were inhibited. Simultaneous dual somato-dendritic recordings from GCs showed that somatic hyperpolarization accelerated the repolarization phase of dendritic bAP in the proximal region whereas the rising phase and peak amplitude was not affected. We hypothesize that the larger driving force for calcium ions during the faster repolarization can contribute to the increasing in calcium signals. Employment of previously recorded dendritic bAP waveforms from hyperpolarized membrane potential as voltage command evoked larger calcium currents in nucleated patches compared to bAP waveform from the same recording at depolarized membrane potential. Furthermore, addition of native, high-voltage activated, inactivating potassium conductance by somatic dynamic clamp

  15. Influence of temperature fluctuations during cryopreservation on vital parameters, differentiation potential, and transgene expression of placental multipotent stromal cells.

    Science.gov (United States)

    Pogozhykh, Denys; Pogozhykh, Olena; Prokopyuk, Volodymyr; Kuleshova, Larisa; Goltsev, Anatoliy; Blasczyk, Rainer; Mueller, Thomas

    2017-03-11

    Successful implementation of rapidly advancing regenerative medicine approaches has led to high demand for readily available cellular suspensions. In particular, multipotent stromal cells (MSCs) of placental origin have shown therapeutic efficiency in the treatment of numerous pathologies of varied etiology. Up to now, cryopreservation is the only effective way to preserve the viability and unique properties of such cells in the long term. However, practical biobanking is often associated with repeated temperature fluctuations or interruption of a cold chain due to various technical, transportation, and stocking events. While biochemical processes are expected to be suspended during cryopreservation, such temperature fluctuations may lead to accumulation of stress as well as to periodic release of water fractions in the samples, possibly leading to damage during long-term storage. In this study, we performed a comprehensive analysis of changes in cell survival, vital parameters, and differentiation potential, as well as transgene expression of placental MSCs after temperature fluctuations within the liquid nitrogen steam storage, mimicking long-term preservation in practical biobanking, transportation, and temporal storage. It was shown that viability and metabolic parameters of placental MSCs did not significantly differ after temperature fluctuations in the range from -196 °C to -100 °C in less than 20 cycles in comparison to constant temperature storage. However, increasing the temperature range to -80 °C as well as increasing the number of cycles leads to significant lowering of these parameters after thawing. The number of apoptotic changes increases depending on the number of cycles of temperature fluctuations. Besides, adhesive properties of the cells after thawing are significantly compromised in the samples subjected to temperature fluctuations during storage. Differentiation potential of placental MSCs was not compromised after cryopreservation

  16. Tramadol, but not its major metabolite (mono-O-demethyl tramadol) depresses compound action potentials in frog sciatic nerves

    Science.gov (United States)

    Katsuki, R; Fujita, T; Koga, A; Liu, T; Nakatsuka, T; Nakashima, M; Kumamoto, E

    2006-01-01

    Background and purpose: Although tramadol is known to exhibit a local anaesthetic effect, how tramadol exerts this effect is not understood fully. Experimental approach: The effects of tramadol and its metabolite mono-O-demethyl-tramadol (M1) on compound action potentials (CAPs) were examined by applying the air-gap method to frog sciatic nerves, and the results were compared with those of other local anaesthetics, lidocaine and ropivacaine. Key results: Tramadol reduced the peak amplitude of the CAP in a dose-dependent manner (IC50=2.3 mM). On the other hand, M1 (1–2 mM), which exhibits a higher affinity for μ-opioid receptors than tramadol, did not affect CAPs. These effects of tramadol were resistant to the non-selective opioid receptor antagonist naloxone and the μ-opioid receptor agonist, DAMGO, did not affect CAPs. This tramadol action was not affected by a combination of the noradrenaline uptake inhibitor, desipramine, and the 5-hydroxytryptamine uptake inhibitor, fluoxetine. Lidocaine and ropivacaine also concentration-dependently reduced CAP peak amplitudes with IC50 values of 0.74 and 0.34 mM, respectively. Conclusions and implications: These results indicate that tramadol reduces the peak amplitude of CAP in peripheral nerve fibres with a potency which is less than those of lidocaine and ropivacaine, whereas M1 has much less effect on CAPs. This action of tramadol was not produced by activation of μ-opioid receptors nor by inhibition of noradrenaline and 5-hydroxytryptamine uptake. It is suggested that the methyl group present in tramadol but not in M1 may play an important role in producing nerve conduction block. PMID:16921387

  17. Cordycepin Decreases Compound Action Potential Conduction of Frog Sciatic Nerve In Vitro Involving Ca2+-Dependent Mechanisms

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    Li-Hua Yao

    2015-01-01

    Full Text Available Cordycepin has been widely used in oriental countries to maintain health and improve physical performance. Compound nerve action potential (CNAP, which is critical in signal conduction in the peripheral nervous system, is necessary to regulate physical performance, including motor system physiological and pathological processes. Therefore, regulatory effects of cordycepin on CNAP conduction should be elucidated. In this study, the conduction ability of CNAP in isolated frog sciatic nerves was investigated. Results revealed that cordycepin significantly decreased CNAP amplitude and conductive velocity in a reversible and concentration-dependent manner. At 50 mg/L cordycepin, CNAP amplitude and conductive velocity decreased by 62.18 ± 8.06% and 57.34% ± 6.14% compared with the control amplitude and conductive velocity, respectively. However, the depressive action of cordycepin on amplitude and conductive velocity was not observed in Ca2+-free medium or in the presence of Ca2+ channel blockers (CdCl2/LaCl3. Pretreatment with L-type Ca2+ channel antagonist (nifedipine/deltiazem also blocked cordycepin-induced responses; by contrast, T-type and P-type Ca2+ channel antagonists (Ni2+ failed to block such responses. Therefore, cordycepin decreased the conduction ability of CNAP in isolated frog sciatic nerves via L-type Ca2+ channel-dependent mechanism.

  18. Non-steady state mass action dynamics without rate constants: dynamics of coupled reactions using chemical potentials

    Science.gov (United States)

    Cannon, William R.; Baker, Scott E.

    2017-10-01

    Comprehensive and predictive simulation of coupled reaction networks has long been a goal of biology and other fields. Currently, metabolic network models that utilize enzyme mass action kinetics have predictive power but are limited in scope and application by the fact that the determination of enzyme rate constants is laborious and low throughput. We present a statistical thermodynamic formulation of the law of mass action for coupled reactions at both steady states and non-stationary states. The formulation uses chemical potentials instead of rate constants. When used to model deterministic systems, the method corresponds to a rescaling of the time dependent reactions in such a way that steady states can be reached on the same time scale but with significantly fewer computational steps. The relationships between reaction affinities, free energy changes and generalized detailed balance are central to the discussion. The significance for applications in systems biology are discussed as is the concept and assumption of maximum entropy production rate as a biological principle that links thermodynamics to natural selection.

  19. THE CHANGES OF SOME PHYSIOLOGICAL PARAMETERS IN PRUSSIAN CARP UNDER THE ACTION OF THE FOLPAN 80 WDG AND THE PROTECTIVE ROLE OF THIOUREA

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    Gabriela Zgurschi

    2012-12-01

    Full Text Available This study was carried out to analyze the effects of sublethal and lethal concentrations of Folpan 80 WDG (30x10-5g Folpan 80 WDG /l water, 6x10-4g Folpan 80WDG /l water and 1‰ thiourea on some physiological parameters (oxygen consumption, breathing frequency on prussian carp (Carassius auratus gibelio Bloch 1782. The subacute and acute toxicity of Folpan 80 WDG fungicide and thiourea was evaluated in glass aquaria under semystatic conditions. Folpan 80 WDG produced, in all organized experimental variants a decrease in respiratory frequency and consumption of oxygen in the case of prussian carp, the more powerful the higher the concentration of the toxic was. Prussian carp anemia could be due to hypoxia that was induced by injuring the gills, as the red-pink colour of the gills became red-white, and at high concentrations the gills completely lost their red colour, while abundant secretions of mucus and even mucosal detachment with abundant bleeding could be observed. The antitoxic action of thiourea manifests itself by the fact that Folpan 80WDG are blocked by SH- groupings isothiourea, the mixture between Folpan 80WDG and thiourea produced no significant changes on the parameters physiological.

  20. Repetitive compound muscle action potentials in electrophysiological diagnosis of congenital myasthenic syndromes: A case report and review of literature

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    Kumar R

    2010-01-01

    Full Text Available Congenital myasthenic syndromes (CMSs are a heterogeneous group of disorders, characterized by dysfunction of neuromuscular junction (NMJ transmission. These syndromes are genetically inherited and are present since birth. Some have characteristic clinical or electrodiagnostic features but in many cases determination of the specific form requires genetic studies or specialized morphological and electrophysiological studies on muscle tissue. We report a case of a 4-year-old boy with progressive ptosis and limitation of ocular movements who was diagnosed as slow-channel CMS based on the characteristic electrodiagnostic features. Repetitive compound muscle action potentials (R-CMAPs were recorded after single nerve stimulus, with decremental response after repetitive trains performed at 3 Hz. CMSs are at times clinically difficult to distinguish from acquired myasthenia. The characteristic clinical and electrodiagnostic features help in the diagnosis and enable rational therapy. In this article we discuss the characteristics of synaptic R-CMAPs.

  1. An Empirical Muscle Intracellular Action Potential Model with Multiple Erlang probability Density Functions based on a Modified Newton Method

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    Gyutae Kim

    2013-01-01

    Full Text Available The convolution of the transmembrane current of an excitable cell and a weighting function generates a single fiber action potential (SFAP model by using the volume conductor theory. Here, we propose an empirical muscle IAP model with multiple Erlang probability density functions (PDFs based on a modified Newton method. In addition, we generate SFAPs based on our IAP model and referent sources, and use the peak-to-peak ratios (PPRs of SFAPs for model verification. Through this verification, we find that the relation between an IAP profile and the PPR of its SFAP is consistent with some previous studies, and our IAP model shows close profiles to the referent sources. Moreover, we simulate and discuss some possible ionic activities by using the Erlang PDFs in our IAP model, which might present the underlying activities of ions or their channels during an IAP.

  2. An Empirical Muscle Intracellular Action Potential Model with Multiple Erlang Probability Density Functions based on a Modified Newton Method.

    Science.gov (United States)

    Kim, Gyutae; Ferdjallah, Mohammed M; McKenzie, Frederic D

    2013-01-01

    The convolution of the transmembrane current of an excitable cell and a weighting function generates a single fiber action potential (SFAP) model by using the volume conductor theory. Here, we propose an empirical muscle IAP model with multiple Erlang probability density functions (PDFs) based on a modified Newton method. In addition, we generate SFAPs based on our IAP model and referent sources, and use the peak-to-peak ratios (PPRs) of SFAPs for model verification. Through this verification, we find that the relation between an IAP profile and the PPR of its SFAP is consistent with some previous studies, and our IAP model shows close profiles to the referent sources. Moreover, we simulate and discuss some possible ionic activities by using the Erlang PDFs in our IAP model, which might present the underlying activities of ions or their channels during an IAP.

  3. Promoting HIV Vaccine Research in African American Communities: Does the Theory of Reasoned Action Explain Potential Outcomes of Involvement?

    Science.gov (United States)

    Frew, Paula M; Archibald, Matthew; Martinez, Nina; del Rio, Carlos; Mulligan, Mark J

    2007-01-01

    The HIV/AIDS pandemic continues to challenge the African American community with disproportionate rates of infection, particularly among young women ages 25 to 34 years. Development of a preventive HIV vaccine may bring a substantial turning point in this health crisis. Engagement of the African American community is necessary to improve awareness of the effort and favorably influence attitudes and referent norms. The Theory of Reasoned Action (TRA) may be a useful framework for exploration of community engagement outcomes including future attendance, community mobilization, and study participation. Within the context of HIV vaccine outreach, we conducted a cross-sectional survey in early 2007 with 175 African-American adults (>/= 18 years). Confirmatory factor analysis and structural equation modeling were performed and the findings support the potential of the model in understanding behavioral intentions toward HIV vaccine research.

  4. Tumor Necrosis Factor alpha induced hypoexcitability in rat muscle evidenced in a model of ion currents and action potential.

    Science.gov (United States)

    Guillouët, Maïté; Rannou, Fabrice; Giroux-Metges, Marie-Agnès; Droguet, Mickael; Pennec, Jean-Pierre

    2013-10-01

    Sepsis and Tumor Necrosis Factor alpha (TNFα), a major pro-inflammatory mediator, have previously been shown to induce a decrease in the conductance of voltage-dependent sodium channels (NaV). Moreover, TNFα increased resting membrane potential, leading to hyperpolarization. NaV and resting potential are the two major factors of membrane excitability. Then we hypothesis that TNFα can decrease muscle membrane excitability. To evidence that role of TNFα, we carried out a simulation of the sodium and potassium currents and action potential (AP) of isolated muscle fibre. We used a computer model based on Hodgkin and Huxley equations, but also taking into account the sodium-potassium pump current. Our first aim was to optimise this model in control conditions according to our measurements of currents. Then the model was modified to fit the values measured experimentally in TNFα-containing medium in order to determine the modifications induced in the currents and hence in AP triggering. Our model provides a very good fit with experimental data on the ion currents. Moreover, it clearly shows that the triggering level of AP is increased in TNFα-containing medium, thus corresponding to a decreased excitability. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Resveratrol exhibits a strong cytotoxic activity in cultured cells and has an antiviral action against polyomavirus: potential clinical use

    Directory of Open Access Journals (Sweden)

    Galati Gaspare

    2009-07-01

    Full Text Available Abstract Background Resveratrol is a non flavonoid polyphenol compound present in many plants and fruits and, at especially high concentrations, in the grape berries of Vitis vinifera. This compound has a strong bioactivity and its cytoprotective action has been demonstrated, however at high concentrations the drug exhibits also an effective anti-proliferative action. We recently showed its ability to abolish the effects of oxidative stress in cultured cells. In this work we assayed the bioactivity of resveratrol as antiproliferative and antiviral drug in cultured fibroblasts. Studies by other Authors showed that this natural compound inhibits the proliferation of different viruses such as herpes simplex, varicella-zoster and influenza A. The results presented here show an evident toxic activity of the drug at high concentrations, on the other hand at sub-cytotoxic concentrations, resveratrol can effectively inhibit the synthesis of polyomavirus DNA. A possible interpretation is that, due to the damage caused by resveratrol to the plasma membrane, the transfer of the virus from the endoplasmic reticulum to the nucleus, may be hindered thus inhibiting the production of viral DNA. Methods The mouse fibroblast line 3T6 and the human tumor line HL60 were used throughout the work. Cell viability and vital cell count were assessed respectively, by the MTT assay and Trypan Blue staining. Cytotoxic properties and evaluation of viral DNA production by agarose gel electrophoresis were performed according to standard protocols. Results Our results show a clear dose dependent both cytotoxic and antiviral effect of resveratrol respectively at high and low concentrations. The cytotoxic action is exerted towards a stabilized cell-line (3T6 as well as a tumor-line (HL60. Furthermore the antiviral action is evident after the phase of virion entry, therefore data suggest that the drug acts during the synthesis of the viral progeny DNA. Conclusion Resveratrol is

  6. Effect of acute stretch injury on action potential and network activity of rat neocortical neurons in culture.

    Science.gov (United States)

    Magou, George C; Pfister, Bryan J; Berlin, Joshua R

    2015-10-22

    The basis for acute seizures following traumatic brain injury (TBI) remains unclear. Animal models of TBI have revealed acute hyperexcitablility in cortical neurons that could underlie seizure activity, but studying initiating events causing hyperexcitability is difficult in these models. In vitro models of stretch injury with cultured cortical neurons, a surrogate for TBI, allow facile investigation of cellular changes after injury but they have only demonstrated post-injury hypoexcitability. The goal of this study was to determine if neuronal hyperexcitability could be triggered by in vitro stretch injury. Controlled uniaxial stretch injury was delivered to a spatially delimited region of a spontaneously active network of cultured rat cortical neurons, yielding a region of stretch-injured neurons and adjacent regions of non-stretched neurons that did not directly experience stretch injury. Spontaneous electrical activity was measured in non-stretched and stretch-injured neurons, and in control neuronal networks not subjected to stretch injury. Non-stretched neurons in stretch-injured cultures displayed a three-fold increase in action potential firing rate and bursting activity 30-60 min post-injury. Stretch-injured neurons, however, displayed dramatically lower rates of action potential firing and bursting. These results demonstrate that acute hyperexcitability can be observed in non-stretched neurons located in regions adjacent to the site of stretch injury, consistent with reports that seizure activity can arise from regions surrounding the site of localized brain injury. Thus, this in vitro procedure for localized neuronal stretch injury may provide a model to study the earliest cellular changes in neuronal function associated with acute post-traumatic seizures. Copyright © 2015. Published by Elsevier B.V.

  7. Spine Calcium Transients Induced by Synaptically-Evoked Action Potentials Can Predict Synapse Location and Establish Synaptic Democracy

    Science.gov (United States)

    Meredith, Rhiannon M.; van Ooyen, Arjen

    2012-01-01

    CA1 pyramidal neurons receive hundreds of synaptic inputs at different distances from the soma. Distance-dependent synaptic scaling enables distal and proximal synapses to influence the somatic membrane equally, a phenomenon called “synaptic democracy”. How this is established is unclear. The backpropagating action potential (BAP) is hypothesised to provide distance-dependent information to synapses, allowing synaptic strengths to scale accordingly. Experimental measurements show that a BAP evoked by current injection at the soma causes calcium currents in the apical shaft whose amplitudes decay with distance from the soma. However, in vivo action potentials are not induced by somatic current injection but by synaptic inputs along the dendrites, which creates a different excitable state of the dendrites. Due to technical limitations, it is not possible to study experimentally whether distance information can also be provided by synaptically-evoked BAPs. Therefore we adapted a realistic morphological and electrophysiological model to measure BAP-induced voltage and calcium signals in spines after Schaffer collateral synapse stimulation. We show that peak calcium concentration is highly correlated with soma-synapse distance under a number of physiologically-realistic suprathreshold stimulation regimes and for a range of dendritic morphologies. Peak calcium levels also predicted the attenuation of the EPSP across the dendritic tree. Furthermore, we show that peak calcium can be used to set up a synaptic democracy in a homeostatic manner, whereby synapses regulate their synaptic strength on the basis of the difference between peak calcium and a uniform target value. We conclude that information derived from synaptically-generated BAPs can indicate synapse location and can subsequently be utilised to implement a synaptic democracy. PMID:22719238

  8. Determining the parameters of Weibull function to estimate the wind power potential in conditions of limited source meteorological data

    Science.gov (United States)

    Fetisova, Yu. A.; Ermolenko, B. V.; Ermolenko, G. V.; Kiseleva, S. V.

    2017-04-01

    We studied the information basis for the assessment of wind power potential on the territory of Russia. We described the methodology to determine the parameters of the Weibull function, which reflects the density of distribution of probabilities of wind flow speeds at a defined basic height above the surface of the earth using the available data on the average speed at this height and its repetition by gradations. The application of the least square method for determining these parameters, unlike the use of graphical methods, allows performing a statistical assessment of the results of approximation of empirical histograms by the Weibull formula. On the basis of the computer-aided analysis of the statistical data, it was shown that, at a fixed point where the wind speed changes at different heights, the range of parameter variation of the Weibull distribution curve is relatively small, the sensitivity of the function to parameter changes is quite low, and the influence of changes on the shape of speed distribution curves is negligible. Taking this into consideration, we proposed and mathematically verified the methodology of determining the speed parameters of the Weibull function at other heights using the parameter computations for this function at a basic height, which is known or defined by the average speed of wind flow, or the roughness coefficient of the geological substrate. We gave examples of practical application of the suggested methodology in the development of the Atlas of Renewable Energy Resources in Russia in conditions of deficiency of source meteorological data. The proposed methodology, to some extent, may solve the problem related to the lack of information on the vertical profile of repeatability of the wind flow speeds in the presence of a wide assortment of wind turbines with different ranges of wind-wheel axis heights and various performance characteristics in the global market; as a result, this methodology can become a powerful tool for

  9. On the potential of 2-D-Video Disdrometer technique to measure micro physical parameters of solid precipitation

    Science.gov (United States)

    Bernauer, F.; Hürkamp, K.; Rühm, W.; Tschiersch, J.

    2015-03-01

    Detailed characterization and classification of precipitation is an important task in atmospheric research. Line scanning 2-D-video disdrometer technique is well established for rain observations. The two orthogonal views taken of each hydrometeor passing the sensitive area of the instrument qualify this technique especially for detailed characterization of non symmetric solid hydrometeors. However, in case of solid precipitation problems related to the matching algorithm have to be considered and the user must be aware of the limited spacial resolution when size and shape descriptors are analyzed. This work has the aim of clarifying the potential of 2-D-video disdrometer technique in deriving size, velocity and shape parameters from single recorded pictures. The need of implementing a matching algorithm suitable for mixed and solid phase precipitation is highlighted as an essential step in data evaluation. For this purpose simple reproducible experiments with solid steel spheres and irregularly shaped styrofoam particles are conducted. Self-consistency of shape parameter measurements is tested in 40 cases of real snow fall. As result it was found, that reliable size and shape characterization with a relative standard deviation of less than 5% is only possible for particles larger than 1 mm. For particles between 0.5 and 1.0 mm the relative standard deviation can grow up to 22% for the volume, 17% for size parameters and 14% for shape descriptors. Testing the adapted matching algorithm with a reproducible experiment with styrofoam particles a mismatch probability of less than 2.5% was found. For shape parameter measurements in case of real solid phase precipitation the 2DVD shows self-consistent behavior.

  10. The effects of propofol on local field potential spectra, action potential firing rate, and their temporal relationship in humans and felines.

    Science.gov (United States)

    Hanrahan, Sara J; Greger, Bradley; Parker, Rebecca A; Ogura, Takahiro; Obara, Shinju; Egan, Talmage D; House, Paul A

    2013-01-01

    Propofol is an intravenous sedative hypnotic, which, acting as a GABAA agonist, results in neocortical inhibition. While propofol has been well studied at the molecular and clinical level, less is known about the effects of propofol at the level of individual neurons and local neocortical networks. We used Utah Electrode Arrays (UEAs) to investigate the effects of propofol anesthesia on action potentials (APs) and local field potentials (LFPs). UEAs were implanted into the neocortex of two humans and three felines. The two human patients and one feline received propofol by bolus injection, while the other two felines received target-controlled infusions. We examined the changes in LFP power spectra and AP firing at different levels of anesthesia. Increased propofol concentration correlated with decreased high-frequency power in LFP spectra and decreased AP firing rates, and the generation of large-amplitude spike-like LFP activity; however, the temporal relationship between APs and LFPs remained relatively consistent at all levels of propofol. The probability that an AP would fire at this local minimum of the LFP increased with propofol administration. The propofol-induced suppression of neocortical network activity allowed LFPs to be dominated by low-frequency spike-like activity, and correlated with sedation and unconsciousness. As the low-frequency spike-like activity increased and the AP-LFP relationship became more predictable firing rate encoding capacity is impaired. This suggests a mechanism for decreased information processing in the neocortex that accounts for propofol-induced unconsciousness.

  11. An analysis of sensitivity of CLIMEX parameters in mapping species potential distribution and the broad-scale changes observed with minor variations in parameters values: an investigation using open-field Solanum lycopersicum and Neoleucinodes elegantalis as an example

    Science.gov (United States)

    da Silva, Ricardo Siqueira; Kumar, Lalit; Shabani, Farzin; Picanço, Marcelo Coutinho

    2017-02-01

    A sensitivity analysis can categorize levels of parameter influence on a model's output. Identifying parameters having the most influence facilitates establishing the best values for parameters of models, providing useful implications in species modelling of crops and associated insect pests. The aim of this study was to quantify the response of species models through a CLIMEX sensitivity analysis. Using open-field Solanum lycopersicum and Neoleucinodes elegantalis distribution records, and 17 fitting parameters, including growth and stress parameters, comparisons were made in model performance by altering one parameter value at a time, in comparison to the best-fit parameter values. Parameters that were found to have a greater effect on the model results are termed "sensitive". Through the use of two species, we show that even when the Ecoclimatic Index has a major change through upward or downward parameter value alterations, the effect on the species is dependent on the selection of suitability categories and regions of modelling. Two parameters were shown to have the greatest sensitivity, dependent on the suitability categories of each species in the study. Results enhance user understanding of which climatic factors had a greater impact on both species distributions in our model, in terms of suitability categories and areas, when parameter values were perturbed by higher or lower values, compared to the best-fit parameter values. Thus, the sensitivity analyses have the potential to provide additional information for end users, in terms of improving management, by identifying the climatic variables that are most sensitive.

  12. Clinical trial involving sufferers and non-sufferers of cervicogenic headache (CGH): potential mechanisms of action of photobiomodulation (Conference Presentation)

    Science.gov (United States)

    Liebert, Ann D.; Bicknell, Brian

    2017-02-01

    Photobiomodulation (PBM) is an effective tool for the management of spinal pain including inflammation of facet joints. Apart from cervical and lumbar joint pain the upper cervical spine facet joint inflammation can result in the CGH (traumatic or atraumatic in origin). This condition affects children, adults and elders and is responsible for 19% of chronic headache and up to 33% of patients in pain clinics. The condition responds well to physiotherapy, facet joint injection, radiofrequency neurotomy and surgery at a rate of 75%. The other 25% being unresponsive to treatment with no identified features of unresponsiveness. In other conditions of chronic unresponsive cervical pain have responded to photobiomodulation at a level of 80% in the short and medium term. A clinical trial was therefore conducted on a cohort of atraumatic patients from the ages of 5-93 (predominantly Neurologist referred / familial sufferers 2/3 generations vertically and laterally) who had responded to a course of PBM and physiotherapy. The CGH sufferers and their non CGH suffering relatives over these generations were then compared for features that distinguish the two groups. Fifty parameters were tested (anthropmetric, movement and neural tension tests included) and there was a noted difference in tandem stance between the groups (.04 significance with repeated measures). As this impairment is common to benign ataxia and migrainous vertigo and in these conditions there is an ion channelopathy (especially potassium channelopathy). A postulated mechanism of action of PBM would involve modulation of ion channels and this is discussed in this presentation.

  13. Correlation of Geoelectric Data with Aquifer Parameters to Delineate the Groundwater Potential of Hard rock Terrain in Central Uganda

    Science.gov (United States)

    Batte, A. G.; Barifaijo, E.; Kiberu, J. M.; Kawule, W.; Muwanga, A.; Owor, M.; Kisekulo, J.

    2010-12-01

    Knowledge of aquifer parameters is essential for management of groundwater resources. Conventionally, these parameters are estimated through pumping tests carried out on water wells. This paper presents a study that was conducted in three villages (Tumba, Kabazi, and Ndaiga) of Nakasongola District, central Uganda to investigate the hydrogeological characteristics of the basement aquifers. Our objective was to correlate surface resistivity data with aquifer properties in order to reveal the groundwater potential in the district. Existing electrical resistivity and borehole data from 20 villages in Nakasongola District were used to correlate the aquifer apparent resistivity ( ρ e) with its hydraulic conductivity ( K e), and aquifer transverse resistance (TR) with its transmissivity ( T e). K e was found to be related to ρ e by; {{Log }}(K_{{e}} ) = - 0.002ρ_{{e}} + 2.692 . Similarly, TR was found to be related to T by; {{TR}} = - 0.07T_{{e}} + 2260 . Using these expressions, aquifer parameters ( T c and K c) were extrapolated from measurements obtained from surface resistivity surveys. Our results show very low resistivities for the presumed water-bearing aquifer zones, possibly because of deteriorating quality of the groundwater and their packing and grain size. Drilling at the preferred VES spots was conducted before the pumping tests to reveal the aquifer characteristics. Aquifer parameters ( T o and K o) as obtained from pumping tests gave values (29,424.7 m2/day, 374.3 m/day), (9,801.1 m2/day, 437.0 m/day), (31,852.4 m2/day, 392.9 m/day). The estimated aquifer parameter ( T c and K c) when extrapolated from surface geoelectrical data gave (7,142.9 m2/day, 381.9 m/day), (28,200.0 m2/day, 463.4 m/day), (19,428.6 m2/day, 459.2 m/day) for Tumba, Kabazi, and Ndaiga villages, respectively. Interestingly, the similarity between the K c and K o pairs was not significantly different. We observed no significant relationships between the T c and T o pairs. The root

  14. Cochlear Nerve Action Potential Monitoring for Preserving Function of an Unseen Cochlear Nerve in Vestibular Schwannoma Surgery.

    Science.gov (United States)

    Ishikawa, Mami; Kojima, Atsuhiro; Terao, Satoshi; Nagai, Mutsumi; Kusaka, Gen; Naritaka, Heiji

    2017-10-01

    Intraoperative monitoring of cochlear nerve action potential (CNAP) has been used in patients with small vestibular schwannoma (<15 mm) to preserve cochlear nerve function. We performed surgery for a larger vestibular schwannoma under CNAP monitoring with the aim of preserving cochlear nerve function, and compared the data with findings from 10 patients with hemifacial spasm who underwent microvascular decompression surgery. We report the case of a patient with a 26-mm vestibular schwannoma and normal hearing function who underwent neurosurgery under electrophysiological monitoring of the facial and cochlear nerves. Amplitudes of evoked facial muscle responses were maintained at approximately 70% during the operation. The latency of wave V on brainstem auditory evoked potential (BAEP) increased by 0.5 ms, and amplitude was maintained at approximately 70% of the value at the beginning of the operation. Latencies of P1, N1, and P2 on CNAP did not change intraoperatively. These latencies were comparable to those of 10 normal patients with hemifacial spasm. CNAP monitoring proved very useful in confirming the location of the cochlear nerve in the operative field and preserving cochlear nerve function. Both facial nerve function and hearing acuity were completely preserved after tumor removal, and wave V latency on BAEP returned to normal and was maintained in the normal range for at least 2 years. CNAP monitoring is extremely useful for preserving the function of the unseen cochlear nerve during vestibular schwannoma surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Potential weathering by freeze-thaw action in alpine rocks in the European Alps during a nine year monitoring period

    Science.gov (United States)

    Kellerer-Pirklbauer, Andreas

    2017-11-01

    A quantification of rock weathering by freeze-thaw processes in alpine rocks requires at least rock temperature data in high temporal resolution, in high quality, and over a sufficient period of time. In this study up to nine years of rock temperature data (2006-2015) from eleven rock monitoring sites in two of the highest mountain ranges of Austria were analyzed. Data were recorded at a half-hourly or hourly logging interval and at rock depths of 3, 10, and 30-40 cm. These data have been used to quantify mean conditions, ranges, and relationships of the potential near-surface weathering by freeze-thaw action considering volumetric-expansion of ice and ice segregation. For the former, freeze-thaw cycles and effective freeze-thaw cycles for frost shattering have been considered. For the latter, the intensity and duration of freezing events as well as time within the 'frost cracking window' have been analyzed. Results show that the eleven sites are in rather extreme topoclimatic positions and hence represent some of the highest and coolest parts of Austria and therefore the Eastern Alps. Only four sites are presumably affected by permafrost. Most sites are influenced by a long-lasting seasonal snow cover. Freeze-thaw cycles and effective freeze-thaw cycles for frost shattering are mainly affecting the near-surface and are unimportant at few tens of centimeters below the rock surface. The lowest temperatures during freezing events and the shortest freezing events have been quantified at all eleven monitoring sites very close to the surface. The time within the frost cracking window decreases in most cases from the rock surface inwards apart from very cold years/sites with very low temperatures close to the surface. As shown by this study and predicted climate change scenarios, assumed warmer rock temperature conditions in the future at alpine rock walls in Austria will lead to less severe freezing events and to shorter time periods within the frost-cracking window

  16. Nanoelectronics-biology frontier: From nanoscopic probes for action potential recording in live cells to three-dimensional cyborg tissues.

    Science.gov (United States)

    Duan, Xiaojie; Fu, Tian-Ming; Liu, Jia; Lieber, Charles M

    2013-08-01

    Semiconductor nanowires configured as the active channels of field-effect transistors (FETs) have been used as detectors for high-resolution electrical recording from single live cells, cell networks, tissues and organs. Extracellular measurements with substrate supported silicon nanowire (SiNW) FETs, which have projected active areas orders of magnitude smaller than conventional microfabricated multielectrode arrays (MEAs) and planar FETs, recorded action potential and field potential signals with high signal-to-noise ratio and temporal resolution from cultured neurons, cultured cardiomyocytes, acute brain slices and whole animal hearts. Measurements made with modulation-doped nanoscale active channel SiNW FETs demonstrate that signals recorded from cardiomyocytes are highly localized and have improved time resolution compared to larger planar detectors. In addition, several novel three-dimensional (3D) transistor probes, which were realized using advanced nanowire synthesis methods, have been implemented for intracellular recording. These novel probes include (i) flexible 3D kinked nanowire FETs, (ii) branched intracellular nanotube SiNW FETs, and (iii) active silicon nanotube FETs. Following phospholipid modification of the probes to mimic the cell membrane, the kinked nanowire, branched intracellular nanotube and active silicon nanotube FET probes recorded full-amplitude intracellular action potentials from spontaneously firing cardiomyocytes. Moreover, these probes demonstrated the capability of reversible, stable, and long-term intracellular recording, thus indicating the minimal invasiveness of the new nanoscale structures and suggesting biomimetic internalization via the phospholipid modification. Simultaneous, multi-site intracellular recording from both single cells and cell networks were also readily achieved by interfacing independently addressable nanoprobe devices with cells. Finally, electronic and biological systems have been seamlessly merged in 3D

  17. Polycrystalline structures formed in evaporating droplets as a parameter to test the action of Zincum metallicum 30c in a wheat seed model.

    Science.gov (United States)

    Kokornaczyk, Maria Olga; Baumgartner, Stephan; Betti, Lucietta

    2016-05-01

    Polycrystalline structures formed inside evaporating droplets of different biological fluids have been shown sensitive towards various influences, including ultra high dilutions (UHDs), representing so a new approach potentially useful for basic research in homeopathy. In the present study we tested on a wheat seed model Zincum metallicum 30c efficacy versus lactose 30c and water. Stressed and non-stressed wheat seeds were watered with the three treatments. Seed-leakage droplets were evaporated and the polycrystalline structures formed inside the droplet residues were analyzed for their local connected fractal dimensions (LCFDs) (measure of complexity) using the software ImageJ. We have found significant differences in LCFD values of polycrystalline structures obtained from stressed seeds following the treatments (phomeopathy. Furthermore our results suggest a sensitization of the stressed model towards the treatment action, which is conforming to previous findings. Copyright © 2015 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

  18. Thermophysical parameters of coconut oil and its potential application as the thermal energy storage system in Indonesia

    Science.gov (United States)

    Putri, Widya A.; Fahmi, Zulfikar; Sutjahja, I. M.; Kurnia, D.; Wonorahardjo, S.

    2016-08-01

    The high consumption of electric energy for room air conditioning (AC) system in Indonesia has driven the research of potential thermal energy storage system as a passive temperature controller. The application of coconut oil (CO) as the potential candidate for this purpose has been motivated since its working temperature just around the human thermal comfort zone in the tropical area as Indonesia. In this research we report the time-dependent temperature data of CO, which is adopting the T-history method. The analysis of the data revealed a set of thermophysical parameters, consist of the mean specific heats of the solid and liquid, as well as the latent heat of fusion for the phase change transition. The performance of CO to decrease the air temperature was measured in the thermal chamber. From the results it is shown that the latent phase of CO related to the solid-liquid phase transition show the highest capability in heat absorption, directly showing the potential application of CO as thermal energy storage system in Indonesia.

  19. Correlation of pattern reversal visual evoked potential parameters with the pattern standard deviation in primary open angle glaucoma

    Directory of Open Access Journals (Sweden)

    Ruchi Kothari

    2014-04-01

    Full Text Available AIM:To evaluate whether glaucomatous visual field defect particularly the pattern standard deviation (PSD of Humphrey visual field could be associated with visual evoked potential (VEP parameters of patients having primary open angle glaucoma (POAG.METHODS:Visual field by Humphrey perimetry and simultaneous recordings of pattern reversal visual evoked potential (PRVEP were assessed in 100 patients with POAG. The stimulus configuration for VEP recordings consisted of the transient pattern reversal method in which a black and white checker board pattern was generated (full field and displayed on VEP monitor (colour 14” by an electronic pattern regenerator inbuilt in an evoked potential recorder (RMS EMG EP MARK II.RESULTS:The results of our study indicate that there is a highly significant (P<0.001 negative correlation of P100 amplitude and a statistically significant (P<0.05 positive correlation of N70 latency, P100 latency and N155 latency with the PSD of Humphrey visual field in the subjects of POAG in various age groups as evaluated by Student’s t-test.CONCLUSION:Prolongation of VEP latencies were mirrored by a corresponding increase of PSD values. Conversely, as PSD increases the magnitude of VEP excursions were found to be diminished.

  20. [Effects of BmKIM on sodium current of isolated cardiomyocytes, transmembrane action potential and aconitine induced arrhythmia in vivo in rabbits].

    Science.gov (United States)

    Wang, Teng; Huang, Cong-Xin; Jiang, Hong; Tang, Qi-Zhu; Yang, Bo; Li, Geng-Shan

    2009-02-01

    To investigate the effects of recombinant BmKIM (poly-peptide derived from Asian Scorpion Buthus martensi Karsch) on the sodium current (I(Na)) of isolated ventricular myocytes, transmembrane action potential and aconitine induced arrhythmia in vivo in rabbits. Ventricular myocytes were enzymatically dissociated from adult rabbits. Whole-cell patch-clamp technique was used to record voltage-dependent I(Na). Standard transmembrane action potentials in rabbit hearts in vivo were recorded by using floating glass microelectrodes. Incidence of arrhythmias, the early after depolarization (EAD) and/or delay after depolarization (DAD) were measured in vivo in rabbits post aconitine (100 microg/kg, iv) in the absence or presence of BmKIM (50 microg/kg iv). (1) BmKIM significantly inhibited I(Na) in a voltage-dependent manner and significantly shifted the I-V curves of I(Na) upward. BmKIM left shifted the inactivation curve of I(Na) and voltages at 50% inactivation of I(Na) were changed from (-70.8 +/- 2.6) mV to (-84.8 +/- 3.5) mV (P action potential duration (APD(50) and APD(90)), and reduced action potential amplitude (APA), declined maximum up stroke velocity of action potential (V(max)) in vivo. The Q-T duration was shortened and heart rate significantly increased post BmKIM injection. (3) Incidence of aconitine induced ventricular arrhythmias (77.8%) was significantly reduced by BmKIM (22.2%, P action potential duration and reduce action potential amplitude and reduce the incidence of aconitine induced arrhythmias.

  1. Failure of action potential propagation in sensory neurons: mechanisms and loss of afferent filtering in C-type units after painful nerve injury

    NARCIS (Netherlands)

    Gemes, Geza; Koopmeiners, Andrew; Rigaud, Marcel; Lirk, Philipp; Sapunar, Damir; Bangaru, Madhavi Latha; Vilceanu, Daniel; Garrison, Sheldon R.; Ljubkovic, Marko; Mueller, Samantha J.; Stucky, Cheryl L.; Hogan, Quinn H.

    2013-01-01

    The T-junction of sensory neurons in the dorsal root ganglion (DRG) is a potential impediment to action potential (AP) propagation towards the CNS. Using intracellular recordings from rat DRG neuronal somata during stimulation of the dorsal root, we determined that the maximal rate at which all of

  2. Voltage-gated sodium channels contribute to action potentials and spontaneous contractility in isolated human lymphatic vessels.

    Science.gov (United States)

    Telinius, Niklas; Majgaard, Jens; Kim, Sukhan; Katballe, Niels; Pahle, Einar; Nielsen, Jørn; Hjortdal, Vibeke; Aalkjaer, Christian; Boedtkjer, Donna Briggs

    2015-07-15

    Voltage-gated sodium channels (VGSC) play a key role for initiating action potentials (AP) in excitable cells. VGSC in human lymphatic vessels have not been investigated. In the present study, we report the electrical activity and APs of small human lymphatic collecting vessels, as well as mRNA expression and function of VGSC in small and large human lymphatic vessels. The VGSC blocker TTX inhibited spontaneous contractions in six of 10 spontaneously active vessels, whereas ranolazine, which has a narrower VGSC blocking profile, had no influence on spontaneous activity. TTX did not affect noradrenaline-induced contractions. The VGSC opener veratridine induced contractions in a concentration-dependent manner (0.1-30 μm) eliciting a stable tonic contraction and membrane depolarization to -18 ± 0.6 mV. Veratridine-induced depolarizations and contractions were reversed ∼80% by TTX, and were dependent on Ca(2+) influx via L-type calcium channels and the sodium-calcium exchanger in reverse mode. Molecular analysis determined NaV 1.3 to be the predominantly expressed VGSC isoform. Electrophysiology of mesenteric lymphatics determined the resting membrane potential to be -45 ± 1.7 mV. Spontaneous APs were preceded by a slow depolarization of 5.3 ± 0.6 mV after which a spike was elicited that almost completely repolarized before immediately depolarizing again to plateau. Vessels transiently hyperpolarized prior to returning to the resting membrane potential. TTX application blocked APs. We have shown that VGSC are necessary for initiating and maintaining APs and spontaneous contractions in human lymphatic vessels and our data suggest the main contribution from comes NaV 1.3. We have also shown that activation of these channels augments the contractile activity of the vessels. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  3. Soil Parameters Drive the Structure, Diversity and Metabolic Potentials of the Bacterial Communities Across Temperate Beech Forest Soil Sequences.

    Science.gov (United States)

    Jeanbille, M; Buée, M; Bach, C; Cébron, A; Frey-Klett, P; Turpault, M P; Uroz, S

    2016-02-01

    Soil and climatic conditions as well as land cover and land management have been shown to strongly impact the structure and diversity of the soil bacterial communities. Here, we addressed under a same land cover the potential effect of the edaphic parameters on the soil bacterial communities, excluding potential confounding factors as climate. To do this, we characterized two natural soil sequences occurring in the Montiers experimental site. Spatially distant soil samples were collected below Fagus sylvatica tree stands to assess the effect of soil sequences on the edaphic parameters, as well as the structure and diversity of the bacterial communities. Soil analyses revealed that the two soil sequences were characterized by higher pH and calcium and magnesium contents in the lower plots. Metabolic assays based on Biolog Ecoplates highlighted higher intensity and richness in usable carbon substrates in the lower plots than in the middle and upper plots, although no significant differences occurred in the abundance of bacterial and fungal communities along the soil sequences as assessed using quantitative PCR. Pyrosequencing analysis of 16S ribosomal RNA (rRNA) gene amplicons revealed that Proteobacteria, Acidobacteria and Bacteroidetes were the most abundantly represented phyla. Acidobacteria, Proteobacteria and Chlamydiae were significantly enriched in the most acidic and nutrient-poor soils compared to the Bacteroidetes, which were significantly enriched in the soils presenting the higher pH and nutrient contents. Interestingly, aluminium, nitrogen, calcium, nutrient availability and pH appeared to be the best predictors of the bacterial community structures along the soil sequences.

  4. Clinical usefulness of controlled attenuation parameter to screen hepatic steatosis for potential donor of living donor liver transplant.

    Science.gov (United States)

    Hong, Young Mi; Yoon, Ki Tae; Cho, Mong; Chu, Chong Woo; Rhu, Je Ho; Yang, Kwang Ho; Lee, Jun Woo

    2017-07-01

    Hepatic steatosis is associated with an increased risk of graft loss. Although the controlled attenuation parameter (CAP), a process based on transient elastography, has been suggested as a noninvasive method of assessing hepatic steatosis, to date, there is no study on the usefulness of CAP as a single screening tool for detecting hepatic steatosis in potential living donor liver. We evaluated the accuracy of CAP for detecting hepatic steatosis in potential liver donors. All potential donors of living-donor liver transplantation who underwent a CAP assessment and ultrasonography-guided liver biopsy were enrolled. The steatosis grades were as follows: S0 less than 5%; S1, 5-33%; S2, 34-66%; and S3, more than 66%. According to the liver biopsies, 19 (34.5%) patients had S0, 30 (54.5%) patients had S1, and 6 (11.0%) patients had S2. The CAP value was correlated positively with BMI (r=0.242, P=0.01), waist circumference (r=0.268, P=0.006), hip circumference (r=0.334, P=0.001), Magnetic resonance fat signal fraction (r=0.465, P=0.001), and histologic steatosis grade (r=0.542, P=0.001). The area under the receiver operator characteristic curve for the diagnosis of steatosis (≥S2) by CAP was 0.88 (sensitivity 83.3% and specificity 81.6% at a cutoff value of 276 dB/m, PCAP, as a simple and noninvasive preoperative assessment for hepatic steatosis, may be sufficient for identifying and thus excluding significant hepatic steatosis (>33%) in potential liver donors.

  5. Transmural ultrasound imaging of thermal lesion and action potential changes in perfused canine cardiac wedge preparations by high intensity focused ultrasound ablation.

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    Ziqi Wu

    Full Text Available Intra-procedural imaging is important for guiding cardiac arrhythmia ablation. It is difficult to obtain intra-procedural correlation of thermal lesion formation with action potential (AP changes in the transmural plane during ablation. This study tested parametric ultrasound imaging for transmural imaging of lesion and AP changes in high intensity focused ultrasound (HIFU ablation using coronary perfused canine ventricular wedge preparations (n = 13. The preparations were paced from epi/endocardial surfaces and subjected to HIFU application (3.5 MHz, 11 Hz pulse-repetition-frequency, 70% duty cycle, duration 4 s, 3500 W/cm(2, during which simultaneous optical mapping (1 kframes/s using di-4-ANEPPS and ultrasound imaging (30 MHz of the same transmural surface of the wedge were performed. Spatiotemporally correlated AP measurements and ultrasound imaging allowed quantification of the reduction of AP amplitude (APA, shortening of AP duration at 50% repolarization, AP triangulation, decrease of optical AP rise, and change of conduction velocity along tissue depth direction within and surrounding HIFU lesions. The threshold of irreversible change in APA correlating to lesions was determined to be 43 ± 1% with a receiver operating characteristic (ROC area under curve (AUC of 0.96 ± 0.01 (n = 13. Ultrasound imaging parameters such as integrated backscatter, Rayleigh (α and log-normal (σ parameters, cumulative extrema of σ were tested, with the cumulative extrema of σ performing the best in detecting lesion (ROC AUC 0.89 ± 0.01, n = 13 and change of APA (ROC AUC 0.79 ± 0.03, n = 13. In conclusion, characteristic tissue and AP changes in HIFU ablation were identified and spatiotemporally correlated using optical mapping and ultrasound imaging. Parametric ultrasound imaging using cumulative extrema of σ can detect HIFU lesion and APA reduction.

  6. Transmural Ultrasound Imaging of Thermal Lesion and Action Potential Changes in Perfused Canine Cardiac Wedge Preparations by High Intensity Focused Ultrasound Ablation

    Science.gov (United States)

    Wu, Ziqi; Gudur, Madhu S. R.; Deng, Cheri X.

    2013-01-01

    Intra-procedural imaging is important for guiding cardiac arrhythmia ablation. It is difficult to obtain intra-procedural correlation of thermal lesion formation with action potential (AP) changes in the transmural plane during ablation. This study tested parametric ultrasound imaging for transmural imaging of lesion and AP changes in high intensity focused ultrasound (HIFU) ablation using coronary perfused canine ventricular wedge preparations (n = 13). The preparations were paced from epi/endocardial surfaces and subjected to HIFU application (3.5 MHz, 11 Hz pulse-repetition-frequency, 70% duty cycle, duration 4 s, 3500 W/cm2), during which simultaneous optical mapping (1 kframes/s) using di-4-ANEPPS and ultrasound imaging (30 MHz) of the same transmural surface of the wedge were performed. Spatiotemporally correlated AP measurements and ultrasound imaging allowed quantification of the reduction of AP amplitude (APA), shortening of AP duration at 50% repolarization, AP triangulation, decrease of optical AP rise, and change of conduction velocity along tissue depth direction within and surrounding HIFU lesions. The threshold of irreversible change in APA correlating to lesions was determined to be 43±1% with a receiver operating characteristic (ROC) area under curve (AUC) of 0.96±0.01 (n = 13). Ultrasound imaging parameters such as integrated backscatter, Rayleigh (α) and log-normal (σ) parameters, cumulative extrema of σ were tested, with the cumulative extrema of σ performing the best in detecting lesion (ROC AUC 0.89±0.01, n = 13) and change of APA (ROC AUC 0.79±0.03, n = 13). In conclusion, characteristic tissue and AP changes in HIFU ablation were identified and spatiotemporally correlated using optical mapping and ultrasound imaging. Parametric ultrasound imaging using cumulative extrema of σ can detect HIFU lesion and APA reduction. PMID:24349337

  7. Changes in the action potential and transient outward potassium current in cardiomyocytes during acute cardiac rejection in rats.

    Science.gov (United States)

    Luo, Wenqi; Jia, Yixin; Zheng, Shuai; Li, Yan; Han, Jie; Meng, Xu

    2017-01-01

    Acute cardiac rejection contributes to the changes in the electrophysiological properties of grafted hearts. However, the electrophysiological changes of cardiomyocytes during acute cardiac rejection are still unknown. An understanding of the electrophysiological mechanisms of cardiomyocytes could improve the diagnosis and treatment of acute cardiac rejection. So it is important to characterize the changes in the action potential ( AP ) and the transient outward potassium current ( I to ) in cardiomyocytes during acute cardiac rejection. Heterotopic heart transplantation was performed in allogeneic [Brown Norway (BN)-to-Lewis] and isogeneic (BN-to-BN) rats. Twenty models were established in each group. Ten recipients were sacrificed at the 2nd day and the other ten recipients were sacrificed at the 4 th day after the operation in each group. Histopathological examinations of the grafted hearts were performed in half of the recipients in each group randomly. The other half of the grafted hearts were excised rapidly and enzymatically dissociated to obtain single cardiomyocytes. The AP and I to current were recorded using the whole cell patch-clamp technique. Forty grafted hearts were successfully harvested and used in experiments. Histologic examination showed mild rejection at the 2 nd day and moderate rejection at the 4 th day in the allogeneic group after cardiac transplantation, while no evidence of histologic lesions of rejection were observed in the isogeneic group. Compared with the isogeneic group, the action potential duration ( APD ) of cardiomyocytes in the allogeneic group was significantly prolonged ( APD 90 was 49.28±5.621 mV in the isogeneic group and 88.08±6.445 mV in the allogeneic group at the 2 nd day, P=0.0016; APD 90 was 59.34±5.183 mV in the isogeneic group and 104.0±9.523 mV in the allogeneic group at the 4 th day, P=0.0064). The current density of I to was significantly decreased at the 4 th day after cardiac transplantation. The APD of

  8. Action Potential Broadening in Capsaicin-Sensitive DRG Neurons from Frequency-Dependent Reduction of Kv3 Current.

    Science.gov (United States)

    Liu, Pin W; Blair, Nathaniel T; Bean, Bruce P

    2017-10-04

    Action potential (AP) shape is a key determinant of cellular electrophysiological behavior. We found that in small-diameter, capsaicin-sensitive dorsal root ganglia neurons corresponding to nociceptors (from rats of either sex), stimulation at frequencies as low as 1 Hz produced progressive broadening of the APs. Stimulation at 10 Hz for 3 s resulted in an increase in AP width by an average of 76 ± 7% at 22°C and by 38 ± 3% at 35°C. AP clamp experiments showed that spike broadening results from frequency-dependent reduction of potassium current during spike repolarization. The major current responsible for frequency-dependent reduction of overall spike-repolarizing potassium current was identified as Kv3 current by its sensitivity to low concentrations of 4-aminopyridine (IC 50 <100 μm) and block by the peptide inhibitor blood depressing substance I (BDS-I). There was a small component of Kv1-mediated current during AP repolarization, but this current did not show frequency-dependent reduction. In a small fraction of cells, there was a component of calcium-dependent potassium current that showed frequency-dependent reduction, but the contribution to overall potassium current reduction was almost always much smaller than that of Kv3-mediated current. These results show that Kv3 channels make a major contribution to spike repolarization in small-diameter DRG neurons and undergo frequency-dependent reduction, leading to spike broadening at moderate firing frequencies. Spike broadening from frequency-dependent reduction in Kv3 current could mitigate the frequency-dependent decreases in conduction velocity typical of C-fiber axons. SIGNIFICANCE STATEMENT Small-diameter dorsal root ganglia (DRG) neurons mediating nociception and other sensory modalities express many types of potassium channels, but how they combine to control firing patterns and conduction is not well understood. We found that action potentials of small-diameter rat DRG neurons showed spike

  9. Potential of pedestrian protection systems--a parameter study using finite element models of pedestrian dummy and generic passenger vehicles.

    Science.gov (United States)

    Fredriksson, Rikard; Shin, Jaeho; Untaroiu, Costin D

    2011-08-01

    To study the potential of active, passive, and integrated (combined active and passive) safety systems in reducing pedestrian upper body loading in typical impact configurations. Finite element simulations using models of generic sedan car fronts and the Polar II pedestrian dummy were performed for 3 impact configurations at 2 impact speeds. Chest contact force, head injury criterion (HIC(15)), head angular acceleration, and the cumulative strain damage measure (CSDM(0.25)) were employed as injury parameters. Further, 3 countermeasures were modeled: an active autonomous braking system, a passive deployable countermeasure, and an integrated system combining the active and passive systems. The auto-brake system was modeled by reducing impact speed by 10 km/h (equivalent to ideal full braking over 0.3 s) and introducing a pitch of 1 degree and in-c