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Sample records for action potential bias

  1. 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.

  2. Dynamic Nigrostriatal Dopamine Biases Action Selection.

    Science.gov (United States)

    Howard, Christopher D; Li, Hao; Geddes, Claire E; Jin, Xin

    2017-03-22

    Dopamine is thought to play a critical role in reinforcement learning and goal-directed behavior, but its function in action selection remains largely unknown. Here we demonstrate that nigrostriatal dopamine biases ongoing action selection. When mice were trained to dynamically switch the action selected at different time points, changes in firing rate of nigrostriatal dopamine neurons, as well as dopamine signaling in the dorsal striatum, were found to be associated with action selection. This dopamine profile is specific to behavioral choice, scalable with interval duration, and doesn't reflect reward prediction error, timing, or value as single factors alone. Genetic deletion of NMDA receptors on dopamine or striatal neurons or optogenetic manipulation of dopamine concentration alters dopamine signaling and biases action selection. These results unveil a crucial role of nigrostriatal dopamine in integrating diverse information for regulating upcoming actions, and they have important implications for neurological disorders, including Parkinson's disease and substance dependence. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Perceptual and performance biases in action selection

    OpenAIRE

    2008-01-01

    When we see an object in the world, there may be a large number of different ways to interact with that object. This large 'visuomotor space' can be constrained through affordances (perceptually available object properties defining potential uses), task demands and the actor's intentions. The effects of perceptual biases can be modified by performance factors, such as a limb's end-state-comfort (ESC; Rosenbaum et al. 1990). We investigated how two other potential performance biases affected i...

  4. Perceptual and performance biases in action selection

    NARCIS (Netherlands)

    Wilson, A.; van Bergen, E.; van Swieten, L.; Kent, S.; Mon-Williams, M.

    2008-01-01

    When we see an object in the world, there may be a large number of different ways to interact with that object. This large 'visuomotor space' can be constrained through affordances (perceptually available object properties defining potential uses), task demands and the actor's intentions. The effect

  5. Perfect Actions with Chemical Potential

    CERN Document Server

    Bietenholz, W

    1998-01-01

    We show how to include a chemical potential \\mu in perfect lattice actions. It turns out that the standard procedure of multiplying the quark fields \\Psi, an example, the case of free fermions with chemical potential is worked out explicitly. Even after truncation, cut-off effects in the pressure and the baryon density are small. Using a (quasi-)perfect action, numerical QCD simulations for non-zero chemical potential become more powerful, because coarse lattices are sufficient for extracting continuum physics.

  6. Postactivation Potentiation Biases Maximal Isometric Strength Assessment

    Directory of Open Access Journals (Sweden)

    Leonardo Coelho Rabello Lima

    2014-01-01

    Full Text Available Postactivation potentiation (PAP is known to enhance force production. Maximal isometric strength assessment protocols usually consist of two or more maximal voluntary isometric contractions (MVCs. The objective of this study was to determine if PAP would influence isometric strength assessment. Healthy male volunteers (n=23 performed two five-second MVCs separated by a 180-seconds interval. Changes in isometric peak torque (IPT, time to achieve it (tPTI, contractile impulse (CI, root mean square of the electromyographic signal during PTI (RMS, and rate of torque development (RTD, in different intervals, were measured. Significant increases in IPT (240.6 ± 55.7 N·m versus 248.9 ± 55.1 N·m, RTD (746 ± 152 N·m·s−1versus 727 ± 158 N·m·s−1, and RMS (59.1 ± 12.2% RMSMAX  versus 54.8 ± 9.4% RMSMAX were found on the second MVC. tPTI decreased significantly on the second MVC (2373 ± 1200 ms versus 2784 ± 1226 ms. We conclude that a first MVC leads to PAP that elicits significant enhancements in strength-related variables of a second MVC performed 180 seconds later. If disconsidered, this phenomenon might bias maximal isometric strength assessment, overestimating some of these variables.

  7. Goal-directed action is automatically biased towards looming motion

    Science.gov (United States)

    Moher, Jeff; Sit, Jonathan; Song, Joo-Hyun

    2014-01-01

    It is known that looming motion can capture attention regardless of an observer’s intentions. Real-world behavior, however, frequently involves not just attentional selection, but selection for action. Thus, it is important to understand the impact of looming motion on goal-directed action to gain a broader perspective on how stimulus properties bias human behavior. We presented participants with a visually-guided reaching task in which they pointed to a target letter presented among non-target distractors. On some trials, one of the pre-masks at the location of the upcoming search objects grew rapidly in size, creating the appearance of a “looming” target or distractor. Even though looming motion did not predict the target location, the time required to reach to the target was shorter when the target loomed compared to when a distractor loomed. Furthermore, reach movement trajectories were pulled towards the location of a looming distractor when one was present, a pull that was greater still when the looming motion was on a collision path with the participant. We also contrast reaching data with data from a similarly designed visual search task requiring keypress responses. This comparison underscores the sensitivity of visually-guided reaching data, as some experimental manipulations, such as looming motion path, affected reach trajectories but not keypress measures. Together, the results demonstrate that looming motion biases visually-guided action regardless of an observer’s current behavioral goals, affecting not only the time required to reach to targets but also the path of the observer’s hand movement itself. PMID:25159287

  8. Assessing atmospheric bias correction for dynamical consistency using potential vorticity

    Science.gov (United States)

    Rocheta, Eytan; Evans, Jason P.; Sharma, Ashish

    2014-12-01

    Correcting biases in atmospheric variables prior to impact studies or dynamical downscaling can lead to new biases as dynamical consistency between the ‘corrected’ fields is not maintained. Use of these bias corrected fields for subsequent impact studies and dynamical downscaling provides input conditions that do not appropriately represent intervariable relationships in atmospheric fields. Here we investigate the consequences of the lack of dynamical consistency in bias correction using a measure of model consistency—the potential vorticity (PV). This paper presents an assessment of the biases present in PV using two alternative correction techniques—an approach where bias correction is performed individually on each atmospheric variable, thereby ignoring the physical relationships that exists between the multiple variables that are corrected, and a second approach where bias correction is performed directly on the PV field, thereby keeping the system dynamically coherent throughout the correction process. In this paper we show that bias correcting variables independently results in increased errors above the tropopause in the mean and standard deviation of the PV field, which are improved when using the alternative proposed. Furthermore, patterns of spatial variability are improved over nearly all vertical levels when applying the alternative approach. Results point to a need for a dynamically consistent atmospheric bias correction technique which results in fields that can be used as dynamically consistent lateral boundaries in follow-up downscaling applications.

  9. Estimating Production Potentials: Expert Bias in Applied Decision Making

    Energy Technology Data Exchange (ETDEWEB)

    L. J. Matthews; L. K. Burggraf (ISU); W. J. Reece (INEEL)

    1998-10-01

    A study was conducted to evaluate how workers predict manufacturing production potentials given positively and negatively framed information. Findings indicate the existence of a bias toward positive information and suggest that this bias may be reduced with experience but is never the less maintained. Experts err in the same way non experts do in differentially processing negative and positive information. Additionally, both experts and non experts tend to overestimate production potentials in a positive direction. The authors propose that these biases should be addressed with further research including cross domain analyses and consideration in training, workplace design, and human performance modeling.

  10. Improved Lattice Actions with Chemical Potential

    CERN Document Server

    Bietenholz, W

    1998-01-01

    We give a prescription how to include a chemical potential \\mu into a general lattice action. This inclusion does not cause any lattice artifacts. Hence its application to an improved - or even perfect - action at \\mu =0 yields an improved resp. perfect action at arbitrary \\mu. For short-ranged improved actions, a good scaling behavior holds over a wide region, and the upper bound for the baryon density - which is known for the standard lattice actions - can be exceeded.

  11. Reduced Affective Biasing of Instrumental Action With tDCS Over the Prefrontal Cortex

    NARCIS (Netherlands)

    Ly, V.; Bergmann, T.O.; Gladwin, T.E.; Volman, I.; Usberti, N.; Cools, R.; Roelofs, K.

    2016-01-01

    BACKGROUND: Instrumental action is well known to be vulnerable to affective value. Excessive transfer of affective value to instrumental action is thought to contribute to psychiatric disorders. The brain region most commonly implicated in overriding such affective biasing of instrumental action is

  12. Potential Sources of Bias in Dual Language Achievement Tests.

    Science.gov (United States)

    Cabello, Beverly

    Potential sources of bias in dual language achievement tests were identified and examined. Content, concepts, and vocabulary presented in monolingual English curricula may differ drastically from those presented in bilingual curricula. The Spanish or English versions of the Comprehensive Tests of Basic Skills (CTBS) were administered to 1259…

  13. Motherhood: a potential source of bias in employment decisions.

    Science.gov (United States)

    Heilman, Madeline E; Okimoto, Tyler G

    2008-01-01

    Results of 2 experimental studies in which job incumbents were said to be applying for promotions to traditionally male positions demonstrated bias against mothers in competence expectations and in screening recommendations. This bias occurred regardless of whether the research participants were students (Study 1) or working people (Study 2). Although anticipated job commitment, achievement striving, and dependability were rated as generally lower for parents than for nonparents, anticipated competence was uniquely low for mothers. Mediational analyses indicated that, as predicted, negativity in competence expectations, not anticipated job commitment or achievement striving, promoted the motherhood bias in screening recommendations; expected deficits in agentic behaviors, not in dependability, were found to fuel these competence expectations. These findings suggest that motherhood can indeed hinder the career advancement of women and that it is the heightened association with gender stereotypes that occurs when women are mothers that is the source of motherhood's potentially adverse consequences. 2008 APA

  14. Giant diffusion of underdamped particles in a biased periodic potential.

    Science.gov (United States)

    Lindner, Benjamin; Sokolov, Igor M

    2016-04-01

    We consider the diffusive properties of Brownian motion in a biased periodic potential. We relate the effective diffusion coefficient to the solution of two coupled time-independent partial differential equations and solve these equations numerically by the matrix-continued-fraction (MCF) method for intermediate values of the temperature and friction coefficient. The weak-noise limit is explored by numerical simulations of the Langevin equations. Here, we identify the regions of parameters for which the diffusion coefficient exponentially grows with inverse temperature. In particular, we demonstrate that there is a finite range of bias forces for which such a growth is observed (region of giant enhancement of diffusion). We also show that at small forces close to the critical range, the diffusion coefficient possesses a pronounced maximum as a function of temperature. All results can be interpreted in the framework of a simple two-state theory incorporating the transition rates between the locked and running solutions.

  15. Stabilization of electron beam spot size by self bias potential

    Energy Technology Data Exchange (ETDEWEB)

    Kwan, T.J.T.; Moir, D.C.; Snell, C.M.; Kang, M.

    1998-12-31

    In high resolution flash x-ray imaging technology the electric field developed between the electron beam and the converter target is large enough to draw ions from the target surface. The ions provide fractional neutralization and cause the electron beam to focus radially inward, and the focal point subsequently moves upstream due to the expansion of the ion column. A self-bias target concept is proposed and verified via computer simulation that the electron charge deposited on the target can generate an electric potential, which can effectively limit the ion motion and thereby stabilize the growth of the spot size. A target chamber using the self bias target concept was designed and tested in the Integrated Test Stand (ITS). The authors have obtained good agreement between computer simulation and experiment.

  16. Correlation of action potentials in adjacent neurons

    CERN Document Server

    Shneider, M N

    2015-01-01

    A possible mechanism for the synchronization of action potential propagation along a bundle of neurons (ephaptic coupling) is considered. It is shown that this mechanism is similar to the salutatory conduction of the action potential between the nodes of Ranvier in myelinated axons. The proposed model allows us to estimate the scale of the correlation, i.e., the distance between neurons in the nervous tissue, wherein their synchronization becomes possible. The possibility for experimental verification of the proposed model of synchronization is discussed.

  17. 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.

  18. The potential for social contextual and group biases in team decision-making: biases, conditions and psychological mechanisms.

    Science.gov (United States)

    Jones, P E; Roelofsma, P H

    2000-08-01

    This paper provides a critical review of social contextual and group biases that are relevant to team decision-making in command and control situations. Motivated by the insufficient level of attention this area has received, the purpose of the paper is to provide an insight into the potential that these types of biases have to affect the decision-making of such teams. The biases considered are: false consensus, groupthink, group polarization and group escalation of commitment. For each bias the following four questions are addressed. What is the descriptive nature of the bias? What factors induce the bias? What psychological mechanisms underlie the bias? What is the relevance of the bias to command and control teams? The analysis suggests that these biases have a strong potential to affect team decisions. Consistent with the nature of team decision-making in command and control situations, all of the biases considered tend to be associated with those decisions that are important or novel and are promoted by time pressure and high levels of uncertainty. A concept unifying these biases is that of the shared mental model, but whereas false consensus emanates from social projection tendencies, the rest emanate from social influence factors. The authors also discuss the 'tricky' distinction between teams and groups and propose a revised definition for command and control team. Finally, the authors emphasize the need for future empirical research in this area to pay additional attention to the social side of cognition and the potential that social biases have to affect team decision-making.

  19. One step ahead: The perceived kinematics of others' actions are biased toward expected goals.

    Science.gov (United States)

    Hudson, Matthew; Nicholson, Toby; Simpson, William A; Ellis, Rob; Bach, Patric

    2016-01-01

    Action observation is often conceptualized in a bottom-up manner, where sensory information activates conceptual (or motor) representations. In contrast, here we show that expectations about an actor's goal have a top-down predictive effect on action perception, biasing it toward these goals. In 3 experiments, participants observed hands reach for or withdraw from objects and judged whether a probe stimulus corresponded to the hand's final position. Before action onset, participants generated action expectations on the basis of either object types (safe or painful, Experiments 1 and 2) or abstract color cues (Experiment 3). Participants more readily mistook probes displaced in a predicted position (relative to unpredicted positions) for the hand's final position, and this predictive bias was larger when the movement and expectation were aligned. These effects were evident for low-level movement and high-level goal expectancies. Expectations bias action observation toward the predicted goals. These results challenge current bottom-up views and support recent predictive models of action observation.

  20. The action potential of Dionaea muscipula Ellis.

    Science.gov (United States)

    Hodick, D; Sievers, A

    1988-04-01

    The intention of this investigation was to acquire more concise information about the nature of the action potential of Dionaea muscipula Ellis and the different types of cells generating and conducting it. It is shown by microelectrode measurements that, besides the sensory cells, all the major tissues of the trap lobes are excitable, firing action potentials with pronounced after-hyperpolarizations. The action potentials are strictly dependent on Ca(2+). Their peak depolarizations are shifted 25-27 mV in a positive direction after a tenfold increase in external Ca(2+) concentration. Perfusions with 1 mM ethylene glycol-bis(β-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) or 1 mM LaCl3 completely inhibit excitability. Magnesium ions only slightly affect the peak depolarizations but considerably prolong action potentials. Sodium azide and 2,4-dinitrophenol also abolish excitation, probably by reducing the intracellular ATP concentration. Furthermore, it is tested whether the sensory cells can be distinguished from the other cells of the trap by their electrical behaviour. The resting potentials of sensory cells (-161±7 mV) and mesophyll cells (-155±8 mV) are of the same magnitude. Changes in external ion concentrations affect resting and action potentials in both cell types in a similar way. Additional freeze-fracture studies of both cell types reveal similar numbers and distributions of intramembrane particles on the fracture faces of the plasma membrane, which is most likely the mechanosensor. These findings stress the view that the high mechanosensitivity of the sensory hair results from its anatomy and not from a specialized perception mechanism. It is proposed that trap closure is triggered by a rise in the cytoplasmic concentration of Ca(2+) or a Ca(2+)-activated regulatory complex, which must exceed a threshold concentration. Since the Ca(2+) influx during a single action potential does not suffice to reach this threshold, at least two stimulations

  1. Action potential broadening in a presynaptic channelopathy

    OpenAIRE

    R. Begum; Bakiri, Y.; Volynski, K. E.; Kullmann, D M

    2016-01-01

    Brain development and interictal function are unaffected in many paroxysmal neurological channelopathies, possibly explained by homoeostatic plasticity of synaptic transmission. Episodic ataxia type 1 is caused by missense mutations of the potassium channel Kv1.1, which is abundantly expressed in the terminals of cerebellar basket cells. Presynaptic action potentials of small inhibitory terminals have not been characterized, and it is not known whether developmental plasticity compensates for...

  2. The healthy cell bias of estrogen action: mitochondrial bioenergetics and neurological implications.

    Science.gov (United States)

    Brinton, Roberta Diaz

    2008-10-01

    The 'healthy cell bias of estrogen action' hypothesis examines the role that regulating mitochondrial function and bioenergetics play in promoting neural health and the mechanistic crossroads that lead to divergent outcomes following estrogen exposure. Estrogen-induced signaling pathways in hippocampal and cortical neurons converge upon the mitochondria to enhance aerobic glycolysis coupled to the citric acid cycle, mitochondrial respiration and ATP generation. Convergence of estrogen-induced signaling onto mitochondria is also a point of vulnerability when activated in diseased neurons which exacerbates degeneration through increased load on dysregulated calcium homeostasis. As the continuum of neurological health progresses from healthy to unhealthy so too do the benefits of estrogen or hormone therapy. The healthy cell bias of estrogen action hypothesis provides a lens through which to assess disparities in outcomes across basic and clinical science and on which to predict outcomes of estrogen interventions for sustaining neurological health and preventing age-associated neurodegenerative diseases such as Alzheimer's.

  3. Lay Evaluation of Financial Experts: The Action Advice Effect and Confirmation Bias

    Directory of Open Access Journals (Sweden)

    Tomasz Zaleskiewicz

    2016-09-01

    Full Text Available The goal of this experimental project was to investigate lay peoples’ perceptions of epistemic authority (EA in the field of finance. EA is defined as the extent to which a source of information is treated as evidence for judgments independently of its objective expertise and based on subjective beliefs. Previous research suggested that EA evaluations are biased and that lay people tend to ascribe higher EA to experts who advise action (in the case of medical experts or confirm clients’ expectations (in the case of politicians. However, there has been no research into biases in lay evaluations of financial experts and this project is aimed to fill this gap. Experiment 1 showed that lay people tended to ascribe greater authority to financial consultants who gave more active advice to clients considering taking out a mortgage. Experiment 2 confirmed the action advice effect found in Experiment 1. However, the outcomes of Experiments 2 and – particularly – 3 suggested that this bias might also be due to clients’ desire to confirm their own opinions. Experiment 2 showed that the action advice effect was moderated by clients’ own opinions on taking loans. Lay people ascribed the greatest EA to the advisor in the scenario in which he advised taking action and where this coincided with the client’s positive opinion on the advisability of taking out a loan. In Experiment 3 only participants with a positive opinion on the financial product ascribed greater authority to experts who recommended it; participants whose opinion was negative tended to rate consultants who advised rejecting the product more highly. To conclude, these three experiments revealed that lay people ascribe higher EA to financial consultants who advise action rather than maintenance of the status quo, but this effect is limited by confirmation bias: when the client’s a priori opinion is salient, greater authority is ascribed to experts whose advice confirms it. In this

  4. Action-specific effects in perception and their potential applications

    OpenAIRE

    Witt, Jessica K.; Linkenauger, Sally; Wickens, Chris

    2016-01-01

    Spatial perception is biased by action. Hills appear steeper and distances appear farther to individuals who would have to exert more effort to transverse the space. Objects appear closer, smaller, and faster when they are easier to obtain. Athletes who are playing better than others see their targets as bigger. These phenomena are collectively known as action-specific effects on perception. In this target article, we review evidence for action-specific effects, including evidence that they r...

  5. Action-potential modulation during axonal conduction.

    Science.gov (United States)

    Sasaki, Takuya; Matsuki, Norio; Ikegaya, Yuji

    2011-02-04

    Once initiated near the soma, an action potential (AP) is thought to propagate autoregeneratively and distribute uniformly over axonal arbors. We challenge this classic view by showing that APs are subject to waveform modulation while they travel down axons. Using fluorescent patch-clamp pipettes, we recorded APs from axon branches of hippocampal CA3 pyramidal neurons ex vivo. The waveforms of axonal APs increased in width in response to the local application of glutamate and an adenosine A(1) receptor antagonist to the axon shafts, but not to other unrelated axon branches. Uncaging of calcium in periaxonal astrocytes caused AP broadening through ionotropic glutamate receptor activation. The broadened APs triggered larger calcium elevations in presynaptic boutons and facilitated synaptic transmission to postsynaptic neurons. This local AP modification may enable axonal computation through the geometry of axon wiring.

  6. Multilinear Biased Discriminant Analysis: A Novel Method for Facial Action Unit Representation

    CERN Document Server

    Khademi, Mahmoud; Manzuri-Shalmani, Mohammad T

    2010-01-01

    In this paper a novel efficient method for representation of facial action units by encoding an image sequence as a fourth-order tensor is presented. The multilinear tensor-based extension of the biased discriminant analysis (BDA) algorithm, called multilinear biased discriminant analysis (MBDA), is first proposed. Then, we apply the MBDA and two-dimensional BDA (2DBDA) algorithms, as the dimensionality reduction techniques, to Gabor representations and the geometric features of the input image sequence respectively. The proposed scheme can deal with the asymmetry between positive and negative samples as well as curse of dimensionality dilemma. Extensive experiments on Cohn-Kanade database show the superiority of the proposed method for representation of the subtle changes and the temporal information involved in formation of the facial expressions. As an accurate tool, this representation can be applied to many areas such as recognition of spontaneous and deliberate facial expressions, multi modal/media huma...

  7. Bias-corrected estimation in potentially mildly explosive autoregressive models

    DEFF Research Database (Denmark)

    Haufmann, Hendrik; Kruse, Robinson

    that the indirect inference approach oers a valuable alternative to other existing techniques. Its performance (measured by its bias and root mean squared error) is balanced and highly competitive across many different settings. A clear advantage is its applicability for mildly explosive processes. In an empirical...

  8. Transient plasma potential in pulsed dual frequency inductively coupled plasmas and effect of substrate biasing

    Science.gov (United States)

    Mishra, Anurag; Yeom, Geun Young

    2016-09-01

    An electron emitting probe in saturated floating potential mode has been used to investigate the temporal evolution of plasma potential and the effect of substrate RF biasing on it for pulsed dual frequency (2 MHz/13.56 MHz) inductively coupled plasma (ICP) source. The low frequency power (P2MHz) has been pulsed at 1 KHz and a duty ratio of 50%, while high frequency power (P13.56MHz) has been used in continuous mode. The substrate has been biased with a separate bias power at (P12.56MHz) Argon has been used as a discharge gas. During the ICP power pulsing, three distinct regions in a typical plasma potential profile, have been identified as `initial overshoot', pulse `on-phase' and pulse `off-phase'. It has been found out that the RF biasing of the substrate significantly modulates the temporal evolution of the plasma potential. During the initial overshoot, plasma potential decreases with increasing RF biasing of the substrate, however it increases with increasing substrate biasing for pulse `on-phase' and `off-phase'. An interesting structure in plasma potential profile has also been observed when the substrate bias is applied and its evolution depends upon the magnitude of bias power. The reason of the evolution of this structure may be the ambipolar diffusion of electron and its dependence on bias power.

  9. Action potential initiation in neocortical inhibitory interneurons.

    Directory of Open Access Journals (Sweden)

    Tun Li

    2014-09-01

    Full Text Available Action potential (AP generation in inhibitory interneurons is critical for cortical excitation-inhibition balance and information processing. However, it remains unclear what determines AP initiation in different interneurons. We focused on two predominant interneuron types in neocortex: parvalbumin (PV- and somatostatin (SST-expressing neurons. Patch-clamp recording from mouse prefrontal cortical slices showed that axonal but not somatic Na+ channels exhibit different voltage-dependent properties. The minimal activation voltage of axonal channels in SST was substantially higher (∼7 mV than in PV cells, consistent with differences in AP thresholds. A more mixed distribution of high- and low-threshold channel subtypes at the axon initial segment (AIS of SST cells may lead to these differences. Surprisingly, NaV1.2 was found accumulated at AIS of SST but not PV cells; reducing NaV1.2-mediated currents in interneurons promoted recurrent network activity. Together, our results reveal the molecular identity of axonal Na+ channels in interneurons and their contribution to AP generation and regulation of network activity.

  10. Action potential broadening in a presynaptic channelopathy

    Science.gov (United States)

    Begum, Rahima; Bakiri, Yamina; Volynski, Kirill E.; Kullmann, Dimitri M.

    2016-07-01

    Brain development and interictal function are unaffected in many paroxysmal neurological channelopathies, possibly explained by homoeostatic plasticity of synaptic transmission. Episodic ataxia type 1 is caused by missense mutations of the potassium channel Kv1.1, which is abundantly expressed in the terminals of cerebellar basket cells. Presynaptic action potentials of small inhibitory terminals have not been characterized, and it is not known whether developmental plasticity compensates for the effects of Kv1.1 dysfunction. Here we use visually targeted patch-clamp recordings from basket cell terminals of mice harbouring an ataxia-associated mutation and their wild-type littermates. Presynaptic spikes are followed by a pronounced afterdepolarization, and are broadened by pharmacological blockade of Kv1.1 or by a dominant ataxia-associated mutation. Somatic recordings fail to detect such changes. Spike broadening leads to increased Ca2+ influx and GABA release, and decreased spontaneous Purkinje cell firing. We find no evidence for developmental compensation for inherited Kv1.1 dysfunction.

  11. Constrained Broyden Dimer Method with Bias Potential for Exploring Potential Energy Surface of Multistep Reaction Process.

    Science.gov (United States)

    Shang, Cheng; Liu, Zhi-Pan

    2012-07-10

    To predict the chemical activity of new matter is an ultimate goal in chemistry. The identification of reaction pathways using modern quantum mechanics calculations, however, often requires a high demand in computational power and good chemical intuition on the reaction. Here, a new reaction path searching method is developed by combining our recently developed transition state (TS) location method, namely, the constrained Broyden dimer method, with a basin-filling method via bias potentials, which allows the system to walk out from the energy traps at a given reaction direction. In the new method, the reaction path searching starts from an initial state without the need for preguessing the TS-like or final state structure and can proceed iteratively to the final state by locating all related TSs and intermediates. In each elementary reaction step, a reaction direction, such as a bond breaking, needs to be specified, the information of which is refined and preserved as a normal mode through biased dimer rotation. The method is tested successfully on the Baker reaction system (50 elementary reactions) with good efficiency and stability and is also applied to the potential energy surface exploration of multistep reaction processes in the gas phase and on the surface. The new method can be applied for the computational screening of new catalytic materials with a minimum requirement of chemical intuition.

  12. Examining Event-Related Potential (ERP correlates of decision bias in recognition memory judgments.

    Directory of Open Access Journals (Sweden)

    Holger Hill

    Full Text Available Memory judgments can be based on accurate memory information or on decision bias (the tendency to report that an event is part of episodic memory when one is in fact unsure. Event related potentials (ERP correlates are important research tools for elucidating the dynamics underlying memory judgments but so far have been established only for investigations of accurate old/new discrimination. To identify the ERP correlates of bias, and observe how these interact with ERP correlates of memory, we conducted three experiments that manipulated decision bias within participants via instructions during recognition memory tests while their ERPs were recorded. In Experiment 1, the bias manipulation was performed between blocks of trials (automatized bias and compared to trial-by-trial shifts of bias in accord with an external cue (flexibly controlled bias. In Experiment 2, the bias manipulation was performed at two different levels of accurate old/new discrimination as the memory strength of old (studied items was varied. In Experiment 3, the bias manipulation was added to another, bottom-up driven manipulation of bias induced via familiarity. In the first two Experiments, and in the low familiarity condition of Experiment 3, we found evidence of an early frontocentral ERP component at 320 ms poststimulus (the FN320 that was sensitive to the manipulation of bias via instruction, with more negative amplitudes indexing more liberal bias. By contrast, later during the trial (500-700 ms poststimulus, bias effects interacted with old/new effects across all three experiments. Results suggest that the decision criterion is typically activated early during recognition memory trials, and is integrated with retrieved memory signals and task-specific processing demands later during the trial. More generally, the findings demonstrate how ERPs can help to specify the dynamics of recognition memory processes under top-down and bottom-up controlled retrieval conditions.

  13. Examining Event-Related Potential (ERP) Correlates of Decision Bias in Recognition Memory Judgments

    Science.gov (United States)

    Hill, Holger; Windmann, Sabine

    2014-01-01

    Memory judgments can be based on accurate memory information or on decision bias (the tendency to report that an event is part of episodic memory when one is in fact unsure). Event related potentials (ERP) correlates are important research tools for elucidating the dynamics underlying memory judgments but so far have been established only for investigations of accurate old/new discrimination. To identify the ERP correlates of bias, and observe how these interact with ERP correlates of memory, we conducted three experiments that manipulated decision bias within participants via instructions during recognition memory tests while their ERPs were recorded. In Experiment 1, the bias manipulation was performed between blocks of trials (automatized bias) and compared to trial-by-trial shifts of bias in accord with an external cue (flexibly controlled bias). In Experiment 2, the bias manipulation was performed at two different levels of accurate old/new discrimination as the memory strength of old (studied) items was varied. In Experiment 3, the bias manipulation was added to another, bottom-up driven manipulation of bias induced via familiarity. In the first two Experiments, and in the low familiarity condition of Experiment 3, we found evidence of an early frontocentral ERP component at 320 ms poststimulus (the FN320) that was sensitive to the manipulation of bias via instruction, with more negative amplitudes indexing more liberal bias. By contrast, later during the trial (500–700 ms poststimulus), bias effects interacted with old/new effects across all three experiments. Results suggest that the decision criterion is typically activated early during recognition memory trials, and is integrated with retrieved memory signals and task-specific processing demands later during the trial. More generally, the findings demonstrate how ERPs can help to specify the dynamics of recognition memory processes under top-down and bottom-up controlled retrieval conditions. PMID

  14. [Potential selection bias in telephone surveys: landline and mobile phones].

    Science.gov (United States)

    Garcia-Continente, Xavier; Pérez-Giménez, Anna; López, María José; Nebot, Manel

    2014-01-01

    The increasing use of mobile phones in the last decade has decreased landline telephone coverage in Spanish households. This study aimed to analyze sociodemographic characteristics and health indicators by type of telephone service (mobile phone vs. landline or landline and mobile phone). Two telephone surveys were conducted in Spanish samples (February 2010 and February 2011). Multivariate logistic regression analyses were performed to analyze differences in the main sociodemographic characteristics and health indicators according to the type of telephone service available in Spanish households. We obtained 2027 valid responses (1627 landline telephones and 400 mobile phones). Persons contacted through a mobile phone were more likely to be a foreigner, to belong to the manual social class, to have a lower educational level, and to be a smoker than those contacted through a landline telephone. The profile of the population that has only a mobile phone differs from that with a landline telephone. Therefore, telephone surveys that exclude mobile phones could show a selection bias. Copyright © 2013 SESPAS. Published by Elsevier Espana. All rights reserved.

  15. 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.

  16. Reduction in plasma potential by applying negative DC cathode bias in RF magnetron sputtering

    Science.gov (United States)

    Isomura, Masao; Yamada, Toshinori; Osuga, Kosuke; Shindo, Haruo

    2016-11-01

    We applied a negative DC bias voltage to the cathode of an RF magnetron sputtering system and successfully reduced the plasma potential in both argon plasma and hydrogen-diluted argon plasma. The crystallinity of the deposited Ge films is improved by increasing the negative DC bias voltage. It is indicated that the reduction in plasma potential is effective for reducing the plasma damage on deposited materials, caused by the electric potential between the plasma and substrates. In addition, the deposition rate is increased by the increased electric potential between the plasma and the cathode owing to the negative DC bias voltage. The present method successfully gives us higher speed and lower damage sputtering deposition. The increased electric potential between the plasma and the cathode suppresses the evacuation of electrons from the plasma and also enhances the generation of secondary electrons on the cathode. These probably suppress the electron loss from the plasma and result in the reduction in plasma potential.

  17. 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.

  18. University students' psychopathology: correlates and the examiner's potential bias effect

    Directory of Open Access Journals (Sweden)

    Helena Espirito Santo

    2015-02-01

    Aims: the main objective was to verify if there is a difference on psychopathological symptoms between two groups questioned by two different examiners, controlling for the potential role of social desirability, and other potential covariates. Additionally, we want to assess the level of psychopathology and its socio-demographic correlates.Methods: 185 Coimbra's university students completed the Brief Symptom Inventory/BSI and the Marlowe-Crowne Social Desirability Scale. In one group the examiner was of the same age and academic status as the students, while in the other group the examiner was older and a teacher. We studied the psychopathological correlates with Pearson, point-biserial correlations, and qui-square analyses, and we controlled the potential role of covariates through Quade non-parametric ANCOVAs. Results: The level of distress was lower in comparison with other investigations. Women had higher level of distress and more symptoms of somatization, anxiety, phobic anxiety, obsessive-compulsion, and depression. The students that live a higher distance from home had more anxiety and obsessive-compulsive symptoms. The group assessed by the younger examiner scored higher in distress and in some BSI factors, and had lower levels on social desirability. Conclusions: Sex and distance from home seem important factors for university students' mental health. However, the examiner does have an influence in the evaluation, probably because of social desirability, suggesting that the examiner's characteristics should be given in investigations involving university students.

  19. Learning from potentially-biased statistics: Household inflation perceptions and expectations in Argentina

    OpenAIRE

    Cruces, Guillermo; Perez-Truglia, Ricardo; Cavallo, Alberto F.

    2016-01-01

    When forming expectations, households may be influenced by perceived bias in the information they receive. In this paper, we study how individuals learn from potentially biased statistics using data from both a natural experiment and a survey experiment during a period (2007–15) when the government of Argentina was manipulating official inflation statistics. This period is interesting because attention was being given to inflation information and both official and unofficial s...

  20. Potential Vascular Actions of 2-Methoxyestradiol

    Science.gov (United States)

    Dubey, Raghvendra K.; Jackson, Edwin K.

    2009-01-01

    2-Methoxyestradiol (2-ME) is a biologically active metabolite of 17β-estradiol that appears to inhibit key processes associated with cell replication in vitro; it may have potent growth-inhibitory effects on proliferating cells, including smooth muscle cells and endothelial cells and may be antiangiogenic. Because of these potential roles for 2-ME, its lack of cytotoxicity and its low estrogenic activity, we hypothesize that 2-ME could be a valuable therapeutic molecule for prevention and treatment of cardiovascular diseases. Whether 2-ME is as efficacious in vivo as it is in vitro at modulating vascular processes remains controversial. Here we discuss recent developments regarding mechanisms by which 2-ME might regulate vascular activity and angiogenesis and speculate on the therapeutic implications of these developments. PMID:19734053

  1. 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

  2. Priming status-legitimizing beliefs: Examining the impact on perceived anti-White bias, zero-sum beliefs, and support for Affirmative Action among White people.

    Science.gov (United States)

    Wellman, Joseph D; Liu, Xi; Wilkins, Clara L

    2016-09-01

    The current research examines how status-legitimizing beliefs (SLBs) influence White people's perceptions of anti-White bias, endorsement of zero-sum beliefs, and support for Affirmative Action. We suggest that SLBs perpetuate inequality by increasing White people's perceptions of zero-sum beliefs and anti-White bias, which in turn lead to decreased support for Affirmative Action. White individuals primed with SLBs perceived greater anti-White bias, endorsed greater zero-sum beliefs, and indicated less support for Affirmative Action than individuals primed with neutral content. Mediation analysis revealed that the SLB prime decreased support for Affirmative Action by increasing perceptions of anti-White bias. This research offers experimental evidence that SLBs contribute to White people's perceptions of anti-White bias and to decreased support for Affirmative Action.

  3. Are Managed Futures Indices Telling Truth? Biases in CTA Databases and Proposals of Potential Enhancements

    Directory of Open Access Journals (Sweden)

    Adam Zaremba

    2011-07-01

    Full Text Available Managed futures are an alternative asset class which has recently became considerably popular among investment industry. However, due to its characteristics, access to managed futures historical performance statistics is relatively confined. All available information originates from commercial and academic databases, reporting to which is entirely voluntary. This situation results in series of biases which distort the managed futures performance in the eyes of investors. The paper consists of two parts. First, the author reviews and describes various biases that influence the reliability of the managed futures indices and databases. The second section encompasses author’s proposals of potential enhancements, which aim to reduce the impact of the biases in order to derive a benchmark that could better reflect characteristics of managed futures investment from the point of view of a potential investor.

  4. Retraining automatic action tendencies changes alcoholic patients’ approach bias for alcohol and improves treatment outcome

    NARCIS (Netherlands)

    R.W. Wiers; C. Eberl; M. Rinck; E.S. Becker; J. Lindenmeyer

    2011-01-01

    This study tested the effects of a new cognitive-bias modification (CBM) intervention that targeted an approach bias for alcohol in 214 alcoholic inpatients. Patients were assigned to one of two experimental conditions, in which they were explicitly or implicitly trained to make avoidance movements

  5. Retraining Automatic Action Tendencies Changes Alcoholic Patients’ Approach Bias for Alcohol and Improves Treatment Outcome

    NARCIS (Netherlands)

    Wiers, R.W.H.J.; Eberl, C.M.; Rinck, M.; Becker, E.S.; Lindenmeyer, J.

    2011-01-01

    This study tested the effects of a new cognitive-bias modification (CBM) intervention that targeted an approach bias for alcohol in 214 alcoholic inpatients. Patients were assigned to one of two experimental conditions, in which they were explicitly or implicitly trained to make avoidance movements

  6. Introducing "Emotioncy" as a Potential Source of Test Bias: A Mixed Rasch Modeling Study

    Science.gov (United States)

    Pishghadam, Reza; Baghaei, Purya; Seyednozadi, Zahra

    2017-01-01

    This article attempts to present emotioncy as a potential source of test bias to inform the analysis of test item performance. Emotioncy is defined as a hierarchy, ranging from "exvolvement" (auditory, visual, and kinesthetic) to "involvement" (inner and arch), to emphasize the emotions evoked by the senses. This study…

  7. Bias in research.

    Science.gov (United States)

    Simundić, Ana-Maria

    2013-01-01

    By writing scientific articles we communicate science among colleagues and peers. By doing this, it is our responsibility to adhere to some basic principles like transparency and accuracy. Authors, journal editors and reviewers need to be concerned about the quality of the work submitted for publication and ensure that only studies which have been designed, conducted and reported in a transparent way, honestly and without any deviation from the truth get to be published. Any such trend or deviation from the truth in data collection, analysis, interpretation and publication is called bias. Bias in research can occur either intentionally or unintentionally. Bias causes false conclusions and is potentially misleading. Therefore, it is immoral and unethical to conduct biased research. Every scientist should thus be aware of all potential sources of bias and undertake all possible actions to reduce or minimize the deviation from the truth. This article describes some basic issues related to bias in research.

  8. Prejudiced interactions: implicit racial bias reduces predictive simulation during joint action with an out-group avatar.

    Science.gov (United States)

    Sacheli, Lucia Maria; Christensen, Andrea; Giese, Martin A; Taubert, Nick; Pavone, Enea Francesco; Aglioti, Salvatore Maria; Candidi, Matteo

    2015-02-17

    During social interactions people automatically apply stereotypes in order to rapidly categorize others. Racial differences are among the most powerful cues that drive these categorizations and modulate our emotional and cognitive reactivity to others. We investigated whether implicit racial bias may also shape hand kinematics during the execution of realistic joint actions with virtual in- and out-group partners. Caucasian participants were required to perform synchronous imitative or complementary reach-to-grasp movements with avatars that had different skin color (white and black) but showed identical action kinematics. Results demonstrate that stronger visuo-motor interference (indexed here as hand kinematics differences between complementary and imitative actions) emerged: i) when participants were required to predict the partner's action goal in order to on-line adapt their own movements accordingly; ii) during interactions with the in-group partner, indicating the partner's racial membership modulates interactive behaviors. Importantly, the in-group/out-group effect positively correlated with the implicit racial bias of each participant. Thus visuo-motor interference during joint action, likely reflecting predictive embodied simulation of the partner's movements, is affected by cultural inter-individual differences.

  9. 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.

  10. A fast algorithm for estimating actions in triaxial potentials

    Science.gov (United States)

    Sanders, Jason L.; Binney, James

    2015-03-01

    We present an approach to approximating rapidly the actions in a general triaxial potential. The method is an extension of the axisymmetric approach presented by Binney, and operates by assuming that the true potential is locally sufficiently close to some Stäckel potential. The choice of Stäckel potential and associated ellipsoidal coordinates is tailored to each individual input phase-space point. We investigate the accuracy of the method when computing actions in a triaxial Navarro-Frenk-White potential. The speed of the algorithm comes at the expense of large errors in the actions, particularly for the box orbits. However, we show that the method can be used to recover the observables of triaxial systems from given distribution functions to sufficient accuracy for the Jeans equations to be satisfied. Consequently, such models could be used to build models of external galaxies as well as triaxial components of our own Galaxy. When more accurate actions are required, this procedure can be combined with torus mapping to produce a fast convergent scheme for action estimation.

  11. QCD Effective action at high temperature and small chemical potential

    CERN Document Server

    Villavicencio, C

    2007-01-01

    We present a construction of an effective Yang-Mills action for QCD, from the expansion of the fermionic determinant in terms of powers of the chemical potential at high temperature, for the case of massless quarks. We analyze this expansion in the perturbative region and find that it gives extra spurious information. We propose for the non-perturbative sector a simplified effective action which, in principle, contains only the relevant information.

  12. The importance of measuring and accounting for potential biases in respondent-driven samples.

    Science.gov (United States)

    Rudolph, Abby E; Fuller, Crystal M; Latkin, Carl

    2013-07-01

    Respondent-driven sampling (RDS) is often viewed as a superior method for recruiting hard-to-reach populations disproportionately burdened with poor health outcomes. As an analytic approach, it has been praised for its ability to generate unbiased population estimates via post-stratified weights which account for non-random recruitment. However, population estimates generated with RDSAT (RDS Analysis Tool) are sensitive to variations in degree weights. Several assumptions are implicit in the degree weight and are not routinely assessed. Failure to meet these assumptions could result in inaccurate degree measures and consequently result in biased population estimates. We highlight potential biases associated with violating the assumptions implicit in degree weights for the RDSAT estimator and propose strategies to measure and possibly correct for biases in the analysis.

  13. Potential biases in colorectal cancer screening using faecal occult blood test

    DEFF Research Database (Denmark)

    Riboe, Dea Grip; Dogan, Tilde Steen; Brodersen, John

    2013-01-01

    BACKGROUND: Colorectal cancer (CRC) is one of the most common types of cancer in European countries and associated with a high mortality rate. A 16% relative risk reduction (RRR) of mortality was found in a meta-analysis based on four randomized controlled trials (RCT) on CRC screening. The aim...... of this paper was to scrutinize these trials for potential biases and assess their influence on the screening trials. METHODS: The four RCTs were reviewed based on the principles of 'Critical Appraisal of the Medical Literature'. Principal investigators of the four RCTs were contacted to clarify uncertainties...... in their study. Data were collected from The Danish Data Archives. Authors of the Cochrane review were contacted. RESULTS: Six biases were identified, of which five favour screening. Three of the biases identified were specific to CRC screening: type of diagnostic method, place of surgery and diagnostic delay...

  14. 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.

  15. Wushu Sanda: Color bias, home advantage and motor actions analysis in female matches’ from the 13th World Championships

    Directory of Open Access Journals (Sweden)

    Breno Berny Vasconcelos

    2017-05-01

    Full Text Available Introduction: Wushu Sanda is a mixed orientation combat sport in which athletes duel wearing red or black clothes. Despite its popularity, the knowledge about its technical and psychophysiological aspects are scarce. Objective: The aim of this study was to quantify the motor actions and the color bias and home advantage existence possibility in female matches from the 13th World Wushu Championships, held in Indonesia, 2015. Material and methods: In an observational study were analyzed 46 matches involving 55 athletes. Each match was analyzed twice, and were considered 22 possible techniques (5 types of punches, 5 types of kicks and 12 different throws. All the motor actions were registered for each athlete, aside of match outcome, clothing color and continent of origin. Results: From all applied motor actions, 48.2% were punches, 46.9% were kicks and 4.8% were throws. Athletes applied 11±8.67 punches, 10.7±5.63 kicks and 1.1±1.6 throws per round. The number of throwing techniques applied on the first and second rounds was higher in winners (F=10.24, p=0.002 and F=7.82, p=0.006 respectively. No differences were found in motor behavior among distinct competitive phases (F(3;88=1.87; p=0.140; η2p=0.06. Home advantage was observed supporting Asian athletes (χ2=10.12, p=0.038. Color bias was observed supporting athletes who wore red (χ2=8.52, p=0.004, which won a higher number of matches (65%. Conclusions: To the detriment of grappling actions (throws, female international level Wushu Sanda athletes predominantly used striking motor actions (punches and kicks. Winners applied a higher number of throws than losers. Home advantage was observed supporting Asian athletes. Color bias was observed supporting female athletes who wore red.

  16. Publication bias in laboratory animal research: a survey on magnitude, drivers, consequences and potential solutions.

    Directory of Open Access Journals (Sweden)

    Gerben ter Riet

    Full Text Available CONTEXT: Publication bias jeopardizes evidence-based medicine, mainly through biased literature syntheses. Publication bias may also affect laboratory animal research, but evidence is scarce. OBJECTIVES: To assess the opinion of laboratory animal researchers on the magnitude, drivers, consequences and potential solutions for publication bias. And to explore the impact of size of the animals used, seniority of the respondent, working in a for-profit organization and type of research (fundamental, pre-clinical, or both on those opinions. DESIGN: Internet-based survey. SETTING: All animal laboratories in The Netherlands. PARTICIPANTS: Laboratory animal researchers. MAIN OUTCOME MEASURE(S: Median (interquartile ranges strengths of beliefs on 5 and 10-point scales (1: totally unimportant to 5 or 10: extremely important. RESULTS: Overall, 454 researchers participated. They considered publication bias a problem in animal research (7 (5 to 8 and thought that about 50% (32-70 of animal experiments are published. Employees (n = 21 of for-profit organizations estimated that 10% (5 to 50 are published. Lack of statistical significance (4 (4 to 5, technical problems (4 (3 to 4, supervisors (4 (3 to 5 and peer reviewers (4 (3 to 5 were considered important reasons for non-publication (all on 5-point scales. Respondents thought that mandatory publication of study protocols and results, or the reasons why no results were obtained, may increase scientific progress but expected increased bureaucracy. These opinions did not depend on size of the animal used, seniority of the respondent or type of research. CONCLUSIONS: Non-publication of "negative" results appears to be prevalent in laboratory animal research. If statistical significance is indeed a main driver of publication, the collective literature on animal experimentation will be biased. This will impede the performance of valid literature syntheses. Effective, yet efficient systems should be explored to

  17. Action prediction based on anticipatory brain potentials during simulated driving

    Science.gov (United States)

    Khaliliardali, Zahra; Chavarriaga, Ricardo; Gheorghe, Lucian Andrei; Millán, José del R.

    2015-12-01

    Objective. The ability of an automobile to infer the driver’s upcoming actions directly from neural signals could enrich the interaction of the car with its driver. Intelligent vehicles fitted with an on-board brain-computer interface able to decode the driver’s intentions can use this information to improve the driving experience. In this study we investigate the neural signatures of anticipation of specific actions, namely braking and accelerating. Approach. We investigated anticipatory slow cortical potentials in electroencephalogram recorded from 18 healthy participants in a driving simulator using a variant of the contingent negative variation (CNV) paradigm with Go and No-go conditions: count-down numbers followed by ‘Start’/‘Stop’ cue. We report decoding performance before the action onset using a quadratic discriminant analysis classifier based on temporal features. Main results. (i) Despite the visual and driving related cognitive distractions, we show the presence of anticipatory event related potentials locked to the stimuli onset similar to the widely reported CNV signal (with an average peak value of -8 μV at electrode Cz). (ii) We demonstrate the discrimination between cases requiring to perform an action upon imperative subsequent stimulus (Go condition, e.g. a ‘Red’ traffic light) versus events that do not require such action (No-go condition; e.g. a ‘Yellow’ light); with an average single trial classification performance of 0.83 ± 0.13 for braking and 0.79 ± 0.12 for accelerating (area under the curve). (iii) We show that the centro-medial anticipatory potentials are observed as early as 320 ± 200 ms before the action with a detection rate of 0.77 ± 0.12 in offline analysis. Significance. We show for the first time the feasibility of predicting the driver’s intention through decoding anticipatory related potentials during simulated car driving with high recognition rates.

  18. Action potential and contraction of Dionaea muscipula (Venus flytrap).

    Science.gov (United States)

    DI PALMA, J R; MOHL, R; BEST, W

    1961-03-24

    Observation of the action potential and contraction of the leaf of Dionaea muscipula Ellis revealed several interesting phenomena. Two successive stimuli are generally necessary to cause contraction. The first and ineffective stimulus is associated with slow depolarization. The second stimulus has much more rapid depolarization and initiates contraction.

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

    NARCIS (Netherlands)

    Torres Valderrama, A.; Witteveen, J.A.S.; Navarro Jimenez, M.I.; Blom, J.G.

    2015-01-01

    We 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 transmembrane po

  20. 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.

  1. Sodium and potassium conductance changes during a membrane action potential.

    Science.gov (United States)

    Bezanilla, F; Rojas, E; Taylor, R E

    1970-12-01

    1. A method for turning a membrane potential control system on and off in less than 10 musec is described. This method was used to record membrane currents in perfused giant axons from Dosidicus gigas and Loligo forbesi after turning on the voltage clamp system at various times during the course of a membrane action potential.2. The membrane current measured just after the capacity charging transient was found to have an almost linear relation to the controlled membrane potential.3. The total membrane conductance taken from these current-voltage curves was found to have a time course during the action potential similar to that found by Cole & Curtis (1939).4. The instantaneous current voltage curves were linear enough to make it possible to obtain a good estimate of the individual sodium and potassium channel conductances, either algebraically or by clamping to the sodium, or potassium, reversal potentials. Good general agreement was obtained with the predictions of the Hodgkin-Huxley equations.5. We consider these results to constitute the first direct experimental demonstration of the conductance changes to sodium and potassium during the course of an action potential.

  2. Imaging when acting: picture but not word cues induce action-related biases of visual attention.

    Science.gov (United States)

    Wykowska, Agnieszka; Hommel, Bernhard; Schubö, Anna

    2012-01-01

    In line with the Theory of Event Coding (Hommel et al., 2001a), action planning has been shown to affect perceptual processing - an effect that has been attributed to a so-called intentional weighting mechanism (Wykowska et al., 2009; Memelink and Hommel, 2012), whose functional role is to provide information for open parameters of online action adjustment (Hommel, 2010). The aim of this study was to test whether different types of action representations induce intentional weighting to various degrees. To meet this aim, we introduced a paradigm in which participants performed a visual search task while preparing to grasp or to point. The to-be performed movement was signaled either by a picture of a required action or a word cue. We reasoned that picture cues might trigger a more concrete action representation that would be more likely to activate the intentional weighting of perceptual dimensions that provide information for online action control. In contrast, word cues were expected to trigger a more abstract action representation that would be less likely to induce intentional weighting. In two experiments, preparing for an action facilitated the processing of targets in an unrelated search task if they differed from distractors on a dimension that provided information for online action control. As predicted, however, this effect was observed only if action preparation was signaled by picture cues but not if it was signaled by word cues. We conclude that picture cues are more efficient than word cues in activating the intentional weighting of perceptual dimensions, presumably by specifying not only invariant characteristics of the planned action but also the dimensions of action-specific parameters.

  3. Imaging when acting: picture but not word cues induce action-related biases of visual attention

    Directory of Open Access Journals (Sweden)

    Agnieszka eWykowska

    2012-10-01

    Full Text Available In line with the Theory of Event Coding (Hommel et al., 2001, action planning has been shown to affect perceptual processing—an effect that has been attributed to a so-called intentional weighting mechanism (Memelink & Hommel, in press; Wykowska, Schubö, & Hommel, 2009, whose functional role is to provide information for open parameters of online action adjustment (Hommel, 2010. The aim of this study was to test whether different types of action representations induce intentional weighting to various degrees. To meet this aim, we introduced a paradigm in which participants performed a visual search task while preparing to grasp or to point. The to-be performed movement was signaled either by a picture of a required action or a word cue. We reasoned that picture cues might trigger a more concrete action representation that would be more likely to activate the intentional weighting of perceptual dimensions that provide information for online action control. In contrast, word cues were expected to trigger a more abstract action representation that would be less likely to induce intentional weighting. In two experiments, preparing for an action facilitated the processing of targets in an unrelated search task if they differed from distractors on a dimension that provided information for online action control. As predicted, however, this effect was observed only if action preparation was signaled by picture cues but not if it was signaled by word cues. We conclude that picture cues are more efficient than word cues in activating the intentional weighting of perceptual dimensions, presumably by specifying not only invariant characteristics of the planned action but also the dimensions of action-specific parameters.

  4. Response bias-related impairment of early subjective face discrimination in social anxiety disorders: An event-related potential study.

    Science.gov (United States)

    Qi, Yanyan; Gu, Ruolei; Cao, Jianqin; Bi, Xuejing; Wu, Haiyan; Liu, Xun

    2017-02-05

    Considerable research has shown that social anxiety disorder (SAD) is accompanied by various negative cognitive biases, such as social feedback expectancy bias, memory bias, and interpretation bias. However, whether the memory bias in individuals with SAD is actually a manifestation of response bias, and whether such response bias is associated with deficits in face discrimination, remains unclear. In the present study, we investigated response bias (i.e., a tendency to recognize more negative evaluations) to faces with positive (social acceptance) or negative (social rejection) social evaluations in individuals with SAD and healthy controls (HCs) using event-related potentials (ERPs). Behavioral results revealed significant group differences in response bias in the forced-choice recall task, but no difference in overall memory accuracy. ERP results demonstrated that HCs showed a larger N170 to faces that had rejected them as compared to those that had accepted them, but this effect was not evident in the SAD group. Further analysis showed that response bias was correlated with the ΔN170 (rejected - accepted) amplitude. We concluded that the response bias in individuals with SAD is resulted from impairments in early discrimination of social faces, as reflected by the absent early N170 differentiation effect, which was associated with their combined negative biases.

  5. Electrochemical impedance analysis of nanoporous TiO2 electrode at low bias potential

    Institute of Scientific and Technical Information of China (English)

    Sheng Jun Li; Yuan Lin; Zeng Chen; Jing Bo Zhang; Xiao Wen Zhou

    2010-01-01

    TiO2 colloid was prepared by the sol-gel method and was bladed on transparent conduction glass to made nanoporous electrode.The impedance performance of TiO2 electrode was studied at various bias potential.A simplified equivalent circuit was proposed to investigate the charge transport impedance of TiO2 film and good fitting results were obtained.

  6. Attentional biases in children of depressed mothers: An event-related potential (ERP) study.

    Science.gov (United States)

    Gibb, Brandon E; Pollak, Seth D; Hajcak, Greg; Owens, Max

    2016-11-01

    Although a number of studies have reported that children of depressed, compared to nondepressed, parents exhibit biased attention to sad facial stimuli, the direction of this bias remains unclear; some studies find evidence of preferential attention toward sad faces whereas others find evidence of attention avoidance. In the current study, we used event-related potentials (ERPs) to assess children's attention to emotional stimuli using a spatial cueing task. Across all indices of attention bias (N2pc and sustained posterior contralateral negativity [SPCN] time locked to face onset, P3b time locked to probe onset, reaction times [RTs] to probes), children of mothers with a history of major depressive disorder (MDD) during the child's life exhibited less attention to sad faces than children of never depressed mothers. For two of these indices (SPCN and RTs), the attention biases for the offspring of depressed mothers was not specific to sadness and was observed for all emotional expressions. Group differences in the ERP indices were maintained when controlling for the influence of mothers' and children's current symptoms of depression and anxiety, mothers' history of anxiety disorders, and children's history of MDD and anxiety disorders, suggesting that the results are specific to mothers' history of MDD. (PsycINFO Database Record

  7. Studies on the Action Potential From a Thermodynamic Perspective

    DEFF Research Database (Denmark)

    Wang, Tian

    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...... 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...

  8. 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.

  9. Action Alters Object Identification: Wielding a Gun Increases the Bias to See Guns

    Science.gov (United States)

    Witt, Jessica K.; Brockmole, James R.

    2012-01-01

    Stereotypes, expectations, and emotions influence an observer's ability to detect and categorize objects as guns. In light of recent work in action-perception interactions, however, there is another unexplored factor that may be critical: The action choices available to the perceiver. In five experiments, participants determined whether another…

  10. Action Alters Object Identification: Wielding a Gun Increases the Bias to See Guns

    Science.gov (United States)

    Witt, Jessica K.; Brockmole, James R.

    2012-01-01

    Stereotypes, expectations, and emotions influence an observer's ability to detect and categorize objects as guns. In light of recent work in action-perception interactions, however, there is another unexplored factor that may be critical: The action choices available to the perceiver. In five experiments, participants determined whether another…

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

    DEFF Research Database (Denmark)

    Krarup, Christian

    2004-01-01

    , with fiber loss or increased conduction velocity variability changes of the SNAP may be smaller than expected from normal nerve. The biophysical characteristics of sensory and motor fibers differ, and this may to some extent determine divergent pathophysiological changes in sensory and motor fibers......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...

  12. 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......, with fiber loss or increased conduction velocity variability changes of the SNAP may be smaller than expected from normal nerve. The biophysical characteristics of sensory and motor fibers differ, and this may to some extent determine divergent pathophysiological changes in sensory and motor fibers...

  13. Environmental metabarcodes for insects: in silico PCR reveals potential for taxonomic bias.

    Science.gov (United States)

    Clarke, Laurence J; Soubrier, Julien; Weyrich, Laura S; Cooper, Alan

    2014-11-01

    Studies of insect assemblages are suited to the simultaneous DNA-based identification of multiple taxa known as metabarcoding. To obtain accurate estimates of diversity, metabarcoding markers ideally possess appropriate taxonomic coverage to avoid PCR-amplification bias, as well as sufficient sequence divergence to resolve species. We used in silico PCR to compare the taxonomic coverage and resolution of newly designed insect metabarcodes (targeting 16S) with that of existing markers [16S and cytochrome oxidase c subunit I (COI)] and then compared their efficiency in vitro. Existing metabarcoding primers amplified in silico mitochondrial genomes available, whereas new primers targeting 16S provided >90% coverage. Furthermore, metabarcodes targeting COI appeared to introduce taxonomic PCR-amplification bias, typically amplifying a greater percentage of Lepidoptera and Diptera species, while failing to amplify certain orders in silico. To test whether bias predicted in silico was observed in vitro, we created an artificial DNA blend containing equal amounts of DNA from 14 species, representing 11 insect orders and one arachnid. We PCR-amplified the blend using five primer sets, targeting either COI or 16S, with high-throughput amplicon sequencing yielding more than 6 million reads. In vitro results typically corresponded to in silico PCR predictions, with newly designed 16S primers detecting 11 insect taxa present, thus providing equivalent or better taxonomic coverage than COI metabarcodes. Our results demonstrate that in silico PCR is a useful tool for predicting taxonomic bias in mixed template PCR and that researchers should be wary of potential bias when selecting metabarcoding markers.

  14. Explaining the discrepancy between intentions and actions: the case of hypothetical bias in contingent valuation.

    Science.gov (United States)

    Ajzen, Icek; Brown, Thomas C; Carvajal, Franklin

    2004-09-01

    An experiment was designed to account for intention-behavior discrepancies by applying the theory of planned behavior to contingent valuation. College students (N = 160) voted in hypothetical and real payment referenda to contribute $8 to a scholarship fund. Overestimates of willingness to pay in the hypothetical referendum could not be attributed to moderately favorable latent dispositions. Instead, this hypothetical bias was explained by activation of more favorable beliefs and attitudes in the context of a hypothetical rather than a real referendum. A corrective entreaty was found to eliminate this bias by bringing beliefs, attitudes, and intentions in line with those in the real payment situation. As a result, the theory of planned behavior produced more accurate prediction of real payment when participants were exposed to the corrective entreaty.

  15. Zero-Bias Conductance versus Potential Strength of Interface in Ferromagnetic Superconductors

    Institute of Scientific and Technical Information of China (English)

    Hamidreza Emamipour; Jafar Emamipour

    2012-01-01

    We study zero-bias conductance (ZBC) spectra of a normal-metal/insulator/singlet (and triplet) ferromagnetic superconductor as a function of potential strength of interface in the Blonder-Tinkham Klapwijk (BTK) theory framework.We consider possible pairing states including spin singlet s-wave pairing (SWP),spin triplet opposite spin pairing (OSP) and spin triplet equal spin pairing (ESP).It is found that ZBC as a function of potential strength of interface shows a clear difference between SWP,OSP and ESP states.These results may serve as a useful tool for discriminating pairing states in ferromagnetic superconductors.

  16. Ionic channels underlying the ventricular action potential in zebrafish embryo.

    Science.gov (United States)

    Alday, Aintzane; Alonso, Hiart; Gallego, Monica; Urrutia, Janire; Letamendia, Ainhoa; Callol, Carles; Casis, Oscar

    2014-06-01

    Over the last years zebrafish has become a popular model in the study of cardiac physiology, pathology and pharmacology. Recently, the application of the 3Rs regulation and the characteristics of the embryo have reduced the use of adult zebrafish use in many studies. However, the zebrafish embryo cardiac physiology is poorly characterized since most works have used indirect techniques and direct recordings of cardiac action potential and ionic currents are scarce. In order to optimize the zebrafish embryo model, we used electrophysiological, pharmacological and immunofluorescence tools to identify the characteristics and the ionic channels involved in the ventricular action potentials of zebrafish embryos. The application of Na(+) or T-type Ca(+2) channel blockers eliminated the cardiac electrical activity, indicating that the action potential upstroke depends on Na(+) and T-type Ca(+2) currents. The plateau phase depends on L-type Ca(+2) channels since it is abolished by specific blockade. The direct channel blockade indicates that the action potential repolarization and diastolic potential depends on ERG K(+) channels. The presence in the embryonic heart of the Nav1.5, Cav1.2, Cav3.2 and ERG channels was also confirmed by immunofluorescence, while the absence of effect of specific blockers and immunostaining indicate that two K(+) repolarizing currents present in human heart, Ito and IKs, are absent in the embryonic zebrafish heart. Our results describe the ionic channels present and its role in the zebrafish embryo heart and support the use of zebrafish embryos to study human diseases and their use for drug testing.

  17. Publication bias in laboratory animal research: a survey on magnitude, drivers, consequences and potential solutions

    NARCIS (Netherlands)

    Riet, G. ter; Korevaar, D.A.; Leenaars, M.; Sterk, P.J.; Noorden, C.J. van; Bouter, L.M.; Lutter, R.; Oude Elferink, R.P.; Hooft, L.

    2012-01-01

    CONTEXT: Publication bias jeopardizes evidence-based medicine, mainly through biased literature syntheses. Publication bias may also affect laboratory animal research, but evidence is scarce. OBJECTIVES: To assess the opinion of laboratory animal researchers on the magnitude, drivers, consequences a

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

    OpenAIRE

    Casale, Amanda E.; Foust, Amanda J.; Bal, Thierry; McCormick, David A.

    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 o...

  19. Warm body temperature facilitates energy efficient cortical action potentials.

    Directory of Open Access Journals (Sweden)

    Yuguo Yu

    Full Text Available The energy efficiency of neural signal transmission is important not only as a limiting factor in brain architecture, but it also influences the interpretation of functional brain imaging signals. Action potential generation in mammalian, versus invertebrate, axons is remarkably energy efficient. Here we demonstrate that this increase in energy efficiency is due largely to a warmer body temperature. Increases in temperature result in an exponential increase in energy efficiency for single action potentials by increasing the rate of Na(+ channel inactivation, resulting in a marked reduction in overlap of the inward Na(+, and outward K(+, currents and a shortening of action potential duration. This increase in single spike efficiency is, however, counterbalanced by a temperature-dependent decrease in the amplitude and duration of the spike afterhyperpolarization, resulting in a nonlinear increase in the spike firing rate, particularly at temperatures above approximately 35°C. Interestingly, the total energy cost, as measured by the multiplication of total Na(+ entry per spike and average firing rate in response to a constant input, reaches a global minimum between 37-42°C. Our results indicate that increases in temperature result in an unexpected increase in energy efficiency, especially near normal body temperature, thus allowing the brain to utilize an energy efficient neural code.

  20. Biased signaling of lipids and allosteric actions of synthetic molecules for GPR119

    DEFF Research Database (Denmark)

    Hassing, Helle A; Fares, Suzan; Larsen, Olav;

    2016-01-01

    for 2h with the 2-MAG-lipase inhibitor JZL84 doubled the constitutive activity, indicating that endogenous lipids contribute to the apparent constitutive activity. Finally, besides being an agonist, AR231453 acted as a positive allosteric modulator of OEA and increased its potency by 54-fold at 100nM AR......231453. Our studies uncovering broad and biased signaling, masked constitutive activity by endogenous MAGs, and ago-allosteric properties of synthetic ligands may explain why many GPR119 drug-discovery programs have failed so far....

  1. Biased signaling of lipids and allosteric actions of synthetic molecules for GPR119

    DEFF Research Database (Denmark)

    Hassing, Helle A; Fares, Suzan; Larsen, Olav

    2016-01-01

    GPR119 is a Gαs-coupled lipid-sensor in the gut, where it mediates release of incretin hormones from the enteroendocrine cells and in pancreatic α-cells, where it releases insulin. Naturally occurring lipids such as monoacylglycerols (MAGs) and N-acylethanolamines (NAEs), like oleoylethanolamide......231453. Our studies uncovering broad and biased signaling, masked constitutive activity by endogenous MAGs, and ago-allosteric properties of synthetic ligands may explain why many GPR119 drug-discovery programs have failed so far....

  2. Potential for parasite-induced biases in aquatic invertebrate population studies

    Science.gov (United States)

    Fisher, Justin D.L.; Mushet, David M.; Stockwell, Craig A.

    2014-01-01

    Recent studies highlight the need to include estimates of detection/capture probability in population studies. This need is particularly important in studies where detection and/or capture probability is influenced by parasite-induced behavioral alterations. We assessed potential biases associated with sampling a population of the amphipod Gammarus lacustris in the presence of Polymorphus spp. acanthocephalan parasites shown to increase positive phototaxis in their amphipod hosts. We trapped G. lacustris at two water depths (benthic and surface) and compared number of captures and number of parasitized individuals at each depth. While we captured the greatest number of G. lacustris individuals in benthic traps, parasitized individuals were captured most often in surface traps. These results reflect the phototaxic movement of infected individuals from benthic locations to sunlit surface waters. We then explored the influence of varying infection rates on a simulated population held at a constant level of abundance. Simulations resulted in increasingly biased abundance estimates as infection rates increased. Our results highlight the need to consider parasite-induced biases when quantifying detection and/or capture probability in studies of aquatic invertebrate populations.

  3. Action modulated cognition: the influence of sensori-motor experience on the global processing bias.

    Science.gov (United States)

    Herlihey, Tracey A; Black, Sandra E; Ferber, Susanne

    2013-08-01

    Whether we are aware of it or not, cognition is inherently biased. Researchers have attempted to modulate these biases using prism adaptation in both healthy and patient populations. Recent research suggests that prisms themselves might not be necessary; simply interacting with one side of space can produce similar effects (Dupierrix, Alleysson, Ohlmann and Chokron (2008). Brain Research, 1214, 127-135). Here we tested whether sensori-motor interaction with the environment affects aspects of cognition that should at first glance appear to be unrelated. While previous research involved tasks that were largely directional in nature (e.g., line bisection), we chose a task without a directional component, the hierarchical figures task (Navon, (1977). Cognitive Psychology, 9, 353-383). In a sample of healthy young adults, we found that after 5min of lateralized pointing (pointing solely to the left or right side of space), performance on the hierarchical figures task varied significantly as a function of pointing direction: interference from irrelevant global information increased after interacting with the left side of space and decreased after interacting with the right side of space. We discuss the results in relation to a "hemispheric imbalance" hypothesis. Our findings demonstrate that cognition can be readily influenced by interactions with the environment even without artificially distorting normal perceptuo-motor relationships.

  4. Learning How to Manage Bias: A Case Study of Youth Participatory Action Research

    Science.gov (United States)

    Kirshner, Ben; Pozzoboni, Kristen; Jones, Hannah

    2011-01-01

    Youth programs that are organized around intellectually challenging, socially relevant projects create opportunities for deep cognitive engagement. One type of authentic project that deserves attention from applied developmental scientists is youth participatory action research (YPAR), in which participants study a problem relevant to young…

  5. Short-term memory traces for action bias in human reinforcement learning.

    Science.gov (United States)

    Bogacz, Rafal; McClure, Samuel M; Li, Jian; Cohen, Jonathan D; Montague, P Read

    2007-06-11

    Recent experimental and theoretical work on reinforcement learning has shed light on the neural bases of learning from rewards and punishments. One fundamental problem in reinforcement learning is the credit assignment problem, or how to properly assign credit to actions that lead to reward or punishment following a delay. Temporal difference learning solves this problem, but its efficiency can be significantly improved by the addition of eligibility traces (ET). In essence, ETs function as decaying memories of previous choices that are used to scale synaptic weight changes. It has been shown in theoretical studies that ETs spanning a number of actions may improve the performance of reinforcement learning. However, it remains an open question whether including ETs that persist over sequences of actions allows reinforcement learning models to better fit empirical data regarding the behaviors of humans and other animals. Here, we report an experiment in which human subjects performed a sequential economic decision game in which the long-term optimal strategy differed from the strategy that leads to the greatest short-term return. We demonstrate that human subjects' performance in the task is significantly affected by the time between choices in a surprising and seemingly counterintuitive way. However, this behavior is naturally explained by a temporal difference learning model which includes ETs persisting across actions. Furthermore, we review recent findings that suggest that short-term synaptic plasticity in dopamine neurons may provide a realistic biophysical mechanism for producing ETs that persist on a timescale consistent with behavioral observations.

  6. Social Class and Social Action: The Middle-Class Bias of Democratic Theory in Education

    Science.gov (United States)

    Schutz, Aaron

    2008-01-01

    Background: This article examines the emergence of the middle and working classes in America and describes key characteristics of these cultures as they manifest themselves today. It then explores the effects of social class on our conceptions of democracy. Purpose: To help educators understand the relationship between social action strategies and…

  7. Searching for transition paths in multidimensional space with a fixed repulsive bias potential

    Science.gov (United States)

    Trushin, O. S.; Salo, P.; Ala-Nissila, T.; Ying, S. C.

    2004-01-01

    An efficient method for searching for transition paths in a multidimensional configuration space is proposed. It is based on using a fixed, locally repulsive bias potential, which forces the system to move from a given initial state to a different final state. This simple method is very effective in determining nearby configurations and possible transition paths for many-particle systems. Once the approximate transition paths are known, the corresponding activation energies can be computed using, e.g., the nudged elastic band method. The usefulness of the present method is demonstrated for both classical and quantum-mechanical systems.

  8. Tuning an rf-SQUID flux qubit system's potential with magnetic flux bias

    Institute of Scientific and Technical Information of China (English)

    Hua Tao; Xu Wei-Wei; Shi Jian-Xin; An De-Yue; Sun Guo-Zhu; Yu Yang; Wu Pei-Heng

    2012-01-01

    At an extremely low temperature of 20 mK,we measured the loop current in a tunable rf superconducting quantum interference device (SQUID) with a dc-SQUID.By adjusting the magnetic flux applied to the rf-SQUID loop (φf) and the small dc-SQUID (φcjjf),respectively,the potential shape of the system can be fully controlled in situ.Variation in the transition step and overlap size in the switching current with a barrier flux bias are analyzed,from which we can obtain some relevant device parameters and build a model to explain the experimental phenomenon.

  9. Are two-station biased random walkers always potential molecular motors?

    Science.gov (United States)

    Bakalis, Evangelos; Zerbetto, Francesco

    2015-01-12

    The short answer to the title question is no. Despite their tremendous complexity, many nanomachines are simply one-dimensional systems undergoing a biased, that is, unidirectional, walk on a two-minima potential energy curve. The initially prepared state, or station, is higher in energy than the final equilibrium state that is reached after overcoming an energy barrier. All chemical reactions comply with this scheme, which does not necessarily imply that a generic chemical reaction is a potential molecular motor. If the barrier is low, the system may walk back and the motion will have a large purely Brownian component. Alternatively, a large distance from the barrier of either of the two stations may introduce a Brownian component. Starting from a general inequality that leverages on the idea that the amount of heat dissipated along the potential energy curve is a good indication of the effectiveness of the biased walk, we provide guidelines for the selection of the features of artificial molecular motors.

  10. Vanadium compounds biological actions and potential as pharmacological agents.

    Science.gov (United States)

    Tsiani, E; Fantus, I G

    1997-03-01

    Vanadium is an element found in low concentrations in mammals, for which a function remains to be discovered. Over the past century, vanadium compounds have been suggested anecdotally as therapeutic agents for a variety of diseases. The discovery that vanadate inhibits various enzymes, in particular protein tyrosine phosphatases, and mimics many of the biological actions of insulin suggested a potential role in the therapy of diabetes mellitus. Successful use and an enhancement of insulin sensitivity in rodents and human diabetic subjects, as well as the finding that these agents are capable of stimulating metabolic effects while bypassing the insulin receptor and the early steps in insulin action, target these agents preferentially toward type II diabetes mellitus. Long-term safety remains a major concern, as tissue accumulation and relative nonspecificity of enzyme inhibition may result in adverse effects. Continued research into mechanism of action, consequences of chronic administration, and improvement of specificity is warranted. Regardless of their ultimate success or failure as therapeutic agents, vanadium compounds continue to be useful probes of enzyme structure and function in various biological processes. (Trends Endocrinol Metab 1997;8:51-58). (c) 1997, Elsevier Science Inc.

  11. Interlayer transport of an electron in bilayer graphene with phonon-induced lattice distortion in the presence of biased potential

    Institute of Scientific and Technical Information of China (English)

    He Liang-Ming

    2013-01-01

    The interlayer transport of an electron in bilayer graphene influenced by a phonon in the presence of a biased potential is investigated using the tight-binding approach.The in-plane optical mode E2g and out-of-plane optical mode B1g associated with the applied biased potential are considered to compute and discuss the interlayer transport probability of an electron initially localized on the bottom layer at the Dirac point in the Brillouin zone.Without the biased potential,the interlayer transport probability is equal to 0.5 regardless of the phonon displacement except for a few special cases.Applying a biased potential to the layers,we find that in different phonon modes the function of the transport probability with respect to the applied biased potential and phonon displacement is complex and various,but on the whole the transport probability decreases with the increase in the absolute value of the applied biased potential.These phenomena are discussed in detail in this paper.

  12. The persistent sampling bias in developmental psychology: A call to action.

    Science.gov (United States)

    Nielsen, Mark; Haun, Daniel; Kärtner, Joscha; Legare, Cristine H

    2017-10-01

    Psychology must confront the bias in its broad literature toward the study of participants developing in environments unrepresentative of the vast majority of the world's population. Here, we focus on the implications of addressing this challenge, highlight the need to address overreliance on a narrow participant pool, and emphasize the value and necessity of conducting research with diverse populations. We show that high-impact-factor developmental journals are heavily skewed toward publishing articles with data from WEIRD (Western, educated, industrialized, rich, and democratic) populations. Most critically, despite calls for change and supposed widespread awareness of this problem, there is a habitual dependence on convenience sampling and little evidence that the discipline is making any meaningful movement toward drawing from diverse samples. Failure to confront the possibility that culturally specific findings are being misattributed as universal traits has broad implications for the construction of scientifically defensible theories and for the reliable public dissemination of study findings. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Unconscious bias when experts are invited - and the results of conscious action

    Science.gov (United States)

    Stadmark, Johanna; Conley, Daniel J.

    2016-04-01

    Visibility of different kinds is important in academic work. We publish papers, present results at conferences and are invited to give seminars and write contributions and reviews about other scientists' work. A few years back we reacted on the invitation-only sections in two of the leading scientific journals. We asked: "Who are invited to write about other researchers' newly published results?" The short answer could be: Experts in the field. However, we found that it was mainly male experts in the field when we reviewed/categorized the authors of the invitation-only sections News & Views and Perspective in Nature and Science, respectively, during the years 2010 and 2011 (in total 1663 authors). The proportion of female authors was compared to the proportion of female scientists within their respective fields within academia. We found that female scientists were invited less often than their male colleagues. We notified the two journals about the mismatch (Nature 2012: 488) and their encouraging reply was that they needed to improve how they reflect women's contributions to science (Nature 2012: 491). In 2013 and 2014 the invitation-only sections (with in total 1845 authors) had reached parity (compared to the pool of available scientists) for contributions regarding Earth and Environmental Science, and made steps forward for Medical/Biological/Chemical sciences and Physical sciences. By raising awareness about the unconscious biases we all have, e.g. both men and women, we can act to make progress towards parity in science.

  14. ACTION-SPACE CLUSTERING OF TIDAL STREAMS TO INFER THE GALACTIC POTENTIAL

    Energy Technology Data Exchange (ETDEWEB)

    Sanderson, Robyn E.; Helmi, Amina [Kapteyn Astronomical Institute, P.O. Box 800, 9700 AV Groningen (Netherlands); Hogg, David W., E-mail: robyn@astro.columbia.edu [Center for Cosmology and Particle Physics, Department of Physics, New York University, 4 Washington Place, New York, NY 10003 (United States)

    2015-03-10

    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 of stream membership for any star. We exploit the principle that the action distribution of stream stars is most clustered when the potential used to calculate the actions is closest to the true potential. Clustering is quantified with the Kullback-Leibler Divergence (KLD), which also provides conditional uncertainties for our parameter estimates. We show, for toy Gaia-like data in a spherical isochrone potential, that maximizing the KLD of the action distribution relative to a smoother distribution recovers the input potential. The precision depends on the observational errors and number of streams; using K III giants as tracers, we measure the enclosed mass at the average radius of the sample stars accurate to 3% and precise to 20%-40%. Recovery of the scale radius is precise to 25%, biased 50% high by the small galactocentric distance range of stars in our mock sample (1-25 kpc, or about three scale radii, with mean 6.5 kpc). 20-25 streams with at least 100 stars each are required for a stable confidence interval. With radial velocities (RVs) to 100 kpc, all parameters are determined with ∼10% accuracy and 20% precision (1.3% accuracy for the enclosed mass), underlining the need to complete the RV catalog for faint halo stars observed by Gaia.

  15. 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.

  16. Determinants of action potential propagation in cerebellar Purkinje cell axons.

    Science.gov (United States)

    Monsivais, Pablo; Clark, Beverley A; Roth, Arnd; Häusser, Michael

    2005-01-12

    Axons have traditionally been viewed as highly faithful transmitters of action potentials. Recently, however, experimental evidence has accumulated to support the idea that under some circumstances axonal propagation may fail. Cerebellar Purkinje neurons fire highfrequency simple spikes, as well as bursts of spikes in response to climbing fiber activation (the "complex spike"). Here we have visualized the axon of individual Purkinje cells to directly investigate the relationship between somatic spikes and axonal spikes using simultaneous somatic whole-cell and cell-attached axonal patch-clamp recordings at 200-800 microm from the soma. We demonstrate that sodium action potentials propagate at frequencies up to approximately 260 Hz, higher than simple spike rates normally observed in vivo. Complex spikes, however, did not propagate reliably, with usually only the first and last spikes in the complex spike waveform being propagated. On average, only 1.7 +/- 0.2 spikes in the complex spike were propagated during resting firing, with propagation limited to interspike intervals above approximately 4 msec. Hyperpolarization improved propagation efficacy without affecting total axonal spike number, whereas strong depolarization could abolish propagation of the complex spike. These findings indicate that the complex spike waveform is not faithfully transmitted to downstream synapses and that propagation of the climbing fiber response may be modulated by background activity.

  17. Biased information processing in the escalation paradigm: information search and information evaluation as potential mediators of escalating commitment.

    Science.gov (United States)

    Schultze, Thomas; Pfeiffer, Felix; Schulz-Hardt, Stefan

    2012-01-01

    Escalation of commitment denotes decision makers' increased reinvestment of resources in a losing course of action. Despite the relevance of this topic, little is known about how information is processed in escalation situations, that is, whether decision makers who receive negative outcome feedback on their initial decision search for and/or process information biasedly and whether these biases contribute to escalating commitment. Contrary to a widely cited study by E. J. Conlon and J. M. Parks (1987), in 3 experiments, the authors found that biases do not occur on the level of information search. Neither in a direct replication and extension of the original study with largely increased test power (Experiment 1) nor under methodologically improved conditions (Experiments 2 and 3) did decision makers responsible for failure differ from nonresponsible decision makers with regards to information search, and no selective search for information supporting the initial decision or voting for further reinvestment was observed. However, Experiments 3 and 4 show that the evaluation of the previously sought information is biased among participants who were responsible for initiating the course of action. Mediation analyses show that this evaluation bias in favor of reinvestment partially mediated the responsibility effect on escalation of commitment.

  18. Beyond Bias and Barriers: Fulfilling the Potential of Women in Academic Science and Engineering

    Science.gov (United States)

    Agogino, Alice

    2007-04-01

    Review of the report by the National Academies, with a focus on action strategies in the physical sciences. Women face barriers to hiring and promotion in research universities in many fields of science and engineering; a situation that deprives the United States of an important source of talent as the country faces increasingly stiff global competition in higher education, science and technology, and the marketplace. Eliminating gender bias in universities requires immediate, overarching reform and decisive action by university administrators, professional societies, government agencies, and Congress. Forty years ago, women made up only 3 percent of America's scientific and technical workers, but by 2003 they accounted for nearly one-fifth. In addition, women have earned more than half of the bachelor's degrees awarded in science and engineering since 2000. However, their representation on university and college faculties fails to reflect these gains. Among science and engineering Ph.D.s, four times more men than women hold full-time faculty positions. And minority women with doctorates are less likely than white women or men of any racial or ethnic group to be in tenure positions. The report urges higher education organizations and professional societies to form collaborative, self-monitoring body that would recommend standards for faculty recruitment, retention, and promotion; collect data; and track compliance across institutions. A ``report card'' template is provided in the report. To read the report online, add a comment, or purchase hard copy, go to: http://www.engineeringpathway.com/ep/learningresource/summary/index.jhtml?id=94A4929D-F1B2-432E-8167-63335569CB4E.

  19. Early somatosensory event-related potentials reveal attentional bias for internal stimuli in social anxiety.

    Science.gov (United States)

    Kanai, Yoshihiro; Nittono, Hiroshi; Kubo, Kenta; Sasaki-Aoki, Shoko; Iwanaga, Makoto

    2012-03-01

    The present study used event-related brain potentials (ERPs) to investigate allocation of attentional resources to internal and external stimuli in individuals with social anxiety. High and low socially anxious individuals were presented with depictions of various facial expressions or household objects, followed by an internal (vibration presented to the finger) or external probe (the letter "E"). Participants were told that the vibration signals physiological changes and were asked to detect both probes. High socially anxious individuals showed larger front-central N140 amplitudes in response to vibratory internal probes as compared to non-anxious controls. ERPs elicited by picture stimuli and external probes and reaction times in response to both probe types did not differ between high and low social anxiety individuals. Early somatosensory ERPs reveal an attentional bias for internal stimuli that does not appear in overt behavior.

  20. Potential sources of analytical bias and error in selected trace element data-quality analyses

    Science.gov (United States)

    Paul, Angela P.; Garbarino, John R.; Olsen, Lisa D.; Rosen, Michael R.; Mebane, Christopher A.; Struzeski, Tedmund M.

    2016-09-28

    Potential sources of analytical bias and error associated with laboratory analyses for selected trace elements where concentrations were greater in filtered samples than in paired unfiltered samples were evaluated by U.S. Geological Survey (USGS) Water Quality Specialists in collaboration with the USGS National Water Quality Laboratory (NWQL) and the Branch of Quality Systems (BQS).Causes for trace-element concentrations in filtered samples to exceed those in associated unfiltered samples have been attributed to variability in analytical measurements, analytical bias, sample contamination either in the field or laboratory, and (or) sample-matrix chemistry. These issues have not only been attributed to data generated by the USGS NWQL but have been observed in data generated by other laboratories. This study continues the evaluation of potential analytical bias and error resulting from matrix chemistry and instrument variability by evaluating the performance of seven selected trace elements in paired filtered and unfiltered surface-water and groundwater samples collected from 23 sampling sites of varying chemistries from six States, matrix spike recoveries, and standard reference materials.Filtered and unfiltered samples have been routinely analyzed on separate inductively coupled plasma-mass spectrometry instruments. Unfiltered samples are treated with hydrochloric acid (HCl) during an in-bottle digestion procedure; filtered samples are not routinely treated with HCl as part of the laboratory analytical procedure. To evaluate the influence of HCl on different sample matrices, an aliquot of the filtered samples was treated with HCl. The addition of HCl did little to differentiate the analytical results between filtered samples treated with HCl from those samples left untreated; however, there was a small, but noticeable, decrease in the number of instances where a particular trace-element concentration was greater in a filtered sample than in the associated

  1. Pattern recognition computation using action potential timing for stimulus representation

    Science.gov (United States)

    Hopfield, J. J.

    1995-07-01

    A computational model is described in which the sizes of variables are represented by the explicit times at which action potentials occur, rather than by the more usual 'firing rate' of neurons. The comparison of patterns over sets of analogue variables is done by a network using different delays for different information paths. This mode of computation explains how one scheme of neuroarchitecture can be used for very different sensory modalities and seemingly different computations. The oscillations and anatomy of the mammalian olfactory systems have a simple interpretation in terms of this representation, and relate to processing in the auditory system. Single-electrode recording would not detect such neural computing. Recognition 'units' in this style respond more like radial basis function units than elementary sigmoid units.

  2. Pressure wave model for action potential propagation in excitable cells

    CERN Document Server

    Rvachev, M M

    2003-01-01

    Speed of propagation of small-amplitude pressure waves through the cytoplasmic interior of myelinated and unmyelinated axons of different diameters is theoretically estimated and is found to generally agree with the action potential (AP) conduction velocities. This remarkable coincidence allows to surmise a model in which AP spread along axon is propelled not by straggling ionic currents as in the widely accepted local circuit theory, but by mechanoactivation of the membrane ion channels by a traveling pressure pulse. Hydraulic pulses propagating in the viscous axoplasm are calculated to decay over ~1 mm distances, and it is further hypothesized that it is the role of influxing during the AP calcium ions to activate membrane skeletal protein network attached to the membrane cytoplasmic side for a brief radial contraction amplifying the pressure pulse and preventing its decay. The model correctly predicts that the AP conduction velocity should vary as the one-half power of axon diameter for large unmyelinated ...

  3. Dopamine receptor blockade attenuates the general incentive motivational effects of noncontingently delivered rewards and reward-paired cues without affecting their ability to bias action selection.

    Science.gov (United States)

    Ostlund, Sean B; Maidment, Nigel T

    2012-01-01

    Environmental cues affect our behavior in a variety of ways. Despite playing an invaluable role in guiding our daily activities, such cues also appear to trigger the harmful, compulsive behaviors that characterize addiction and other disorders of behavioral control. In instrumental conditioning, rewards and reward-paired cues bias action selection and invigorate reward-seeking behaviors, and appear to do so through distinct neurobehavioral processes. Although reward-paired cues are known to invigorate performance through a dopamine-dependent incentive motivational process, it is not known if dopamine also mediates the influence of rewards and reward-paired cues over action selection. The current study contrasted the effects of systemic administration of the nonspecific dopamine receptor antagonist flupentixol on response invigoration and action bias in Pavlovian-instrumental transfer, a test of cue-elicited responding, and in instrumental reinstatement, a test of noncontingent reward-elicited responding. Hungry rats were trained on two different stimulus-outcome relationships (eg, tone-grain pellets and noise-sucrose solution) and two different action-outcome relationships (eg, left press-grain and right press-sucrose). At test, we found that flupentixol pretreatment blocked the response invigoration generated by the cues but spared their ability to bias action selection to favor the action whose outcome was signaled by the cue being presented. The response-biasing influence of noncontingent reward deliveries was also unaffected by flupentixol. Interestingly, although flupentixol had a modest effect on the immediate response invigoration produced by those rewards, it was particularly potent in countering the lingering enhancement of responding produced by multiple reward deliveries. These findings indicate that dopamine mediates the general incentive motivational effects of noncontingent rewards and reward-paired cues but does not support their ability to bias

  4. Systematic biases on galaxy haloes parameters from Yukawa-like gravitational potentials

    CERN Document Server

    Cardone, V F

    2011-01-01

    A viable alternative to the dark energy as a solution of the cosmic speed up problem is represented by Extended Theories of Gravity. Should this be indeed the case, there will be an impact not only on cosmological scales, but also at any scale, from the Solar System to extragalactic ones. In particular, the gravitational potential can be different from the Newtonian one commonly adopted when computing the circular velocity fitted to spiral galaxies rotation curves. Phenomenologically modelling the modified point mass potential as the sum of a Newtonian and a Yukawa like correction, we simulate observed rotation curves for a spiral galaxy described as the sum of an exponential disc and a NFW dark matter halo. We then fit these curves assuming parameterized halo models (either with an inner cusp or a core) and using the Newtonian potential to estimate the theoretical rotation curve. Such a study allows us to investigate the bias on the disc and halo model parameters induced by the systematic error induced by fo...

  5. Potential sources of analytical bias and error in selected trace element data-quality analyses

    Science.gov (United States)

    Paul, Angela P.; Garbarino, John R.; Olsen, Lisa D.; Rosen, Michael R.; Mebane, Christopher A.; Struzeski, Tedmund M.

    2016-09-28

    Potential sources of analytical bias and error associated with laboratory analyses for selected trace elements where concentrations were greater in filtered samples than in paired unfiltered samples were evaluated by U.S. Geological Survey (USGS) Water Quality Specialists in collaboration with the USGS National Water Quality Laboratory (NWQL) and the Branch of Quality Systems (BQS).Causes for trace-element concentrations in filtered samples to exceed those in associated unfiltered samples have been attributed to variability in analytical measurements, analytical bias, sample contamination either in the field or laboratory, and (or) sample-matrix chemistry. These issues have not only been attributed to data generated by the USGS NWQL but have been observed in data generated by other laboratories. This study continues the evaluation of potential analytical bias and error resulting from matrix chemistry and instrument variability by evaluating the performance of seven selected trace elements in paired filtered and unfiltered surface-water and groundwater samples collected from 23 sampling sites of varying chemistries from six States, matrix spike recoveries, and standard reference materials.Filtered and unfiltered samples have been routinely analyzed on separate inductively coupled plasma-mass spectrometry instruments. Unfiltered samples are treated with hydrochloric acid (HCl) during an in-bottle digestion procedure; filtered samples are not routinely treated with HCl as part of the laboratory analytical procedure. To evaluate the influence of HCl on different sample matrices, an aliquot of the filtered samples was treated with HCl. The addition of HCl did little to differentiate the analytical results between filtered samples treated with HCl from those samples left untreated; however, there was a small, but noticeable, decrease in the number of instances where a particular trace-element concentration was greater in a filtered sample than in the associated

  6. Attention bias in earthquake-exposed survivors: an event-related potential study.

    Science.gov (United States)

    Zhang, Yan; Kong, Fanchang; Han, Li; Najam Ul Hasan, Abbasi; Chen, Hong

    2014-12-01

    The Chinese Wenchuan earthquake, which happened on the 28th of May in 2008, may leave deep invisible scars in individuals. China has a large number of children and adolescents, who tend to be most vulnerable because they are in an early stage of human development and possible post-traumatic psychological distress may have a life-long consequence. Trauma survivors without post-traumatic stress disorder (PTSD) have received little attention in previous studies, especially in event-related potential (ERP) studies. We compared the attention bias to threat stimuli between the earthquake-exposed group and the control group in a masked version of the dot probe task. The target probe presented at the same space location consistent with earthquake-related words was the congruent trial, while in the space location of neutral words was the incongruent trial. Thirteen earthquake-exposed middle school students without PTSD and 13 matched controls were included in this investigation. The earthquake-exposed group showed significantly faster RTs to congruent trials than to incongruent trials. The earthquake-exposed group produced significantly shorter C1 and P1 latencies and larger C1, P1 and P2 amplitudes than the control group. In particular, enhanced P1 amplitude to threat stimuli was observed in the earthquake-exposed group. These findings are in agreement with the prediction that earthquake-exposed survivors have an attention bias to threat stimuli. The traumatic event had a much greater effect on earthquake-exposed survivors even if they showed no PTSD symptoms than individuals in the controls. These results will provide neurobiological evidences for effective intervention and prevention to post-traumatic mental problems. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Melatonin potentiates the anticonvulsant action of phenobarbital in neonatal rats.

    Science.gov (United States)

    Forcelli, Patrick A; Soper, Colin; Duckles, Anne; Gale, Karen; Kondratyev, Alexei

    2013-12-01

    Phenobarbital is the most commonly utilized drug for neonatal seizures. However, questions regarding safety and efficacy of this drug make it particularly compelling to identify adjunct therapies that could boost therapeutic benefit. One potential adjunct therapy is melatonin. Melatonin is used clinically in neonatal and pediatric populations, and moreover, it exerts anticonvulsant actions in adult rats. However, it has not been previously evaluated for anticonvulsant effects in neonatal rats. Here, we tested the hypothesis that melatonin would exert anticonvulsant effects, either alone, or in combination with phenobarbital. Postnatal day (P)7 rats were treated with phenobarbital (0-40mg/kg) and/or melatonin (0-80mg/kg) prior to chemoconvulsant challenge with pentylenetetrazole (100mg/kg). We found that melatonin significantly potentiated the anticonvulsant efficacy of phenobarbital, but did not exert anticonvulsant effects on its own. These data provide additional evidence for the further examination of melatonin as an adjunct therapy in neonatal/pediatric epilepsy. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Ultrafast action potentials mediate kilohertz signaling at a central synapse.

    Science.gov (United States)

    Ritzau-Jost, Andreas; Delvendahl, Igor; Rings, Annika; Byczkowicz, Niklas; Harada, Harumi; Shigemoto, Ryuichi; Hirrlinger, Johannes; Eilers, Jens; Hallermann, Stefan

    2014-10-01

    Fast synaptic transmission is important for rapid information processing. To explore the maximal rate of neuronal signaling and to analyze the presynaptic mechanisms, we focused on the input layer of the cerebellar cortex, where exceptionally high action potential (AP) frequencies have been reported in vivo. With paired recordings between presynaptic cerebellar mossy fiber boutons and postsynaptic granule cells, we demonstrate reliable neurotransmission up to ∼1 kHz. Presynaptic APs are ultrafast, with ∼100 μs half-duration. Both Kv1 and Kv3 potassium channels mediate the fast repolarization, rapidly inactivating sodium channels ensure metabolic efficiency, and little AP broadening occurs during bursts of up to 1.5 kHz. Presynaptic Cav2.1 (P/Q-type) calcium channels open efficiently during ultrafast APs. Furthermore, a subset of synaptic vesicles is tightly coupled to Ca(2+) channels, and vesicles are rapidly recruited to the release site. These data reveal mechanisms of presynaptic AP generation and transmitter release underlying neuronal kHz signaling.

  9. Acute nerve stretch and the compound motor action potential

    Directory of Open Access Journals (Sweden)

    Wolfe Jacob

    2011-08-01

    Full Text Available Abstract In this paper, the acute changes in the compound motor action potential (CMAP during mechanical stretch were studied in hamster sciatic nerve and compared to the changes that occur during compression. In response to stretch, the nerve physically broke when a mean force of 331 gm (3.3 N was applied while the CMAP disappeared at an average stretch force of 73 gm (0.73 N. There were 5 primary measures of the CMAP used to describe the changes during the experiment: the normalized peak to peak amplitude, the normalized area under the curve (AUC, the normalized duration, the normalized velocity and the normalized velocity corrected for the additional path length the impulses travel when the nerve is stretched. Each of these measures was shown to contain information not available in the others. During stretch, the earliest change is a reduction in conduction velocity followed at higher stretch forces by declines in the amplitude of the CMAP. This is associated with the appearance of spontaneous EMG activity. With stretch forces Multiple means of predicting when a change in the CMAP suggests a significant stretch are discussed and it is clear that a multifactorial approach using both velocity and amplitude parameters is important. In the case of pure compression, it is only the amplitude of the CMAP that is critical in predicting which changes in the CMAP are associated with significant compression.

  10. First principles molecular dynamics of metal/water interfaces under bias potential

    Science.gov (United States)

    Pedroza, Luana; Brandimarte, Pedro; Rocha, Alexandre; Fernandez-Serra, Marivi

    2014-03-01

    Understanding the interaction of the water-metal system at an atomic level is extremely important in electrocatalysts for fuel cells, photocatalysis among other systems. The question of the interface energetics involves a detailed study of the nature of the interactions between water-water and water-substrate. A first principles description of all components of the system is the most appropriate methodology in order to advance understanding of electrochemically processes. In this work we describe, using first principles molecular dynamics simulations, the dynamics of a combined surface(Au and Pd)/water system both in the presence and absence of an external bias potential applied to the electrodes, as one would come across in electrochemistry. This is accomplished using a combination of density functional theory (DFT) and non-equilibrium Green's functions methods (NEGF), thus accounting for the fact that one is dealing with an out-of-equilibrium open system, with and without van der Waals interactions. DOE Early Career Award No. DE-SC0003871.

  11. A potential gender bias in assessing quality of life - a standard gamble experiment among university students.

    Science.gov (United States)

    Obaidi, Leath Al; Mahlich, Jörg

    2015-01-01

    There are several methodologies that can be used for evaluating patients' perception of their quality of life. Most commonly, utilities are directly elicited by means of either the time-trade-off or the standard-gamble method. In both methods, risk attitudes determine the quality of life values. Quality of life values among 31 Austrian undergraduate students were elicited by means of the standard gamble approach. The impact of several variables such as gender, side job, length of study, and living arrangements on the quality of life were identified using different types of regression techniques (ordinary least squares, generalized linear model, Betafit). Significant evidence was found that females are associated with a higher quality of life in all specifications of our estimations. The observed gender differences in quality of life can be attributed to a higher degree of risk aversion of women. A higher risk aversion leads to a higher valuation of given health states and a potential gender bias in health economic evaluations. This result could have implications for health policy planners when it comes to budget allocation decisions.

  12. 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.

  13. Circadian- and Light-Dependent Regulation of Resting Membrane Potential and Spontaneous Action Potential Firing of Drosophila Circadian Pacemaker Neurons

    OpenAIRE

    Sheeba, Vasu; Gu, Huaiyu; Sharma, Vijay K.; O'Dowd, Diane K.; Holmes, Todd C

    2007-01-01

    The ventral lateral neurons (LNvs) of adult Drosophila brain express oscillating clock proteins and regulate circadian behavior. Whole cell current-clamp recordings of large LNvs in freshly dissected Drosophila whole brain preparations reveal two spontaneous activity patterns that correlate with two underlying patterns of oscillating membrane potential: tonic and burst firing of sodium-dependent action potentials. Resting membrane potential and spontaneous action potential firing are rapidly ...

  14. Ontogeny of vestibular compound action potentials in the domestic chicken

    Science.gov (United States)

    Jones, S. M.; Jones, T. A.

    2000-01-01

    Compound action potentials of the vestibular nerve were measured from the surface of the scalp in 148 chickens (Gallus domesticus). Ages ranged from incubation day 18 (E18) to 22 days posthatch (P22). Responses were elicited using linear acceleration cranial pulses. Response thresholds decreased at an average rate of -0.45 dB/day. The decrease was best fit by an exponential model with half-maturity time constant of 5.1 days and asymptote of approximately -25.9 dB re:1.0 g/ms. Mean threshold approached within 3 dB of the asymptote by ages P6-P9. Similarly, response latencies decreased exponentially to within 3% of mature values at ages beyond P9. The half-maturity time constant for peripheral response peak latencies P1, N1, and P2 was comparable to thresholds and ranged from approximately 4.6 to 6.2 days, whereas central peaks (N2, P3, and N3) ranged from 2.9 to 3.4 days. Latency-intensity slopes for P1, N1, and P2 tended to decrease with age, reaching mature values within approximately 100 hours of hatching. Amplitudes increased as a function of age with average growth rates for response peaks ranging from 0.04 to 0.09 microV/day. There was no obvious asymptote to the growth of amplitudes over the ages studied. Amplitude-intensity slopes also increased modestly with age. The results show that gravity receptors are responsive to transient cranial stimuli as early as E19 in the chicken embryo. The functional response of gravity receptors continues to develop for many days after all major morphological structures are in place. Distinct maturational processes can be identified in central and peripheral neural relays. Functional improvements during maturation may result from refinements in the receptor epithelia, improvements in central and peripheral synaptic transmission, increased neural myelination, as well as changes in the mechanical coupling between the cranium and receptor organ.

  15. Distribution of Action Potential Duration and T-wave Morphology: a Simulation Study

    CERN Document Server

    Ryzhii, Elena; Wei, Daming

    2009-01-01

    The results of a simulation study of the action potential duration (APD) distribution and T-wave morphology taking into account the midmyocardial cells (M-cells) concept are described. To investigate the effect of M-cells we present a computer model in which ion channel action potential formulations are incorporated into three-dimensional whole heart model. We implemented inhomogeneous continuous action potential duration distribution based on different distributions of maximal slow delayed rectifier current conductance. Using the proposed action potential distribution procedure midmural zeniths with longest action potential length were created as islands of model cells in the depth of thickest areas of ventricular tissue. Different spatial functions on layer indexes were simulated and their influences on electrocardiogram waveforms were analyzed. Changing parameters of ion channel model we varied duration of minimal and maximal action potential and investigated T-wave amplitude, Q-Tpeak and QT intervals vari...

  16. How You Move Is What I See: Planning an Action Biases a Partner’s Visual Search

    Science.gov (United States)

    Dötsch, Dominik; Vesper, Cordula; Schubö, Anna

    2017-01-01

    Activating action representations can modulate perceptual processing of action-relevant dimensions, indicative of a common-coding of perception and action. When two or more agents work together in joint action, individual agents often need to consider not only their own actions and their effects on the world, but also predict the actions of a co-acting partner. If in these situations the action of a partner is represented in a functionally equivalent way to the agent’s own actions, one may also expect interaction effects between action and perception across jointly acting individuals. The present study investigated whether the action of a co-acting partner may modulate an agent’s perception. The “performer” prepared a grasping or pointing movement toward a physical target while the “searcher” performed a visual search task. The performer’s planned action impaired the searcher’s perceptual performance when the search target dimension was relevant to the performer’s movement execution. These results demonstrate an action-induced modulation of perceptual processes across participants and indicate that agents represent their partner’s action by employing the same perceptual system they use to represent an own action. We suggest that task representations in joint action operate along multiple levels of a cross-brain predictive coding system, which provides agents with information about a partner’s actions when they coordinate to reach a common goal.

  17. 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,…

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    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...... 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...

  19. Action potential broadening and frequency-dependent facilitation of calcium signals in pituitary nerve terminals.

    OpenAIRE

    Jackson, M B; Konnerth, A.; Augustine, G.J.

    1991-01-01

    Hormone release from nerve terminals in the neurohypophysis is a sensitive function of action potential frequency. We have investigated the cellular mechanisms responsible for this frequency-dependent facilitation by combining patch clamp and fluorimetric Ca2+ measurements in single neurosecretory terminals in thin slices of the rat posterior pituitary. In these terminals both action potential-induced changes in the intracellular Ca2+ concentration ([Ca2+]i) and action potential duration were...

  20. Effect of a prenylamine analog (MG8926) on spontaneous action potentials in isolated rabbit sinoatrial node.

    Science.gov (United States)

    Nakanishi, H; Matsuoka, I; Ono, T; Yoshida, H; Uchibori, T; Kogi, K

    1996-12-01

    Effects of verapamil, prenylamine and a prenylamine analog, MG8926 on the intracellular spontaneous action potentials recorded from the isolated rabbit sinoatrial (SA) node were studied. Verapamil (1 microM), a selective inhibitor for slow Ca2+ channels, prolonged the cycle length, decreased the rate of diastolic depolarization, the rate of rise of action potential, the amplitude of action potential and the maximal diastolic potential, and usually arrested showing subthreshold fluctuation of the membrane potential within several ten min. Prenylamine (10 microM), a nonselective inhibitor for slow Ca2+ channels, tended to prolong the cycle length to decrease the diastolic depolarization, the rate of rise of action potential, the amplitude of action potential. However, these changes were statistically insignificant. Prenylamine at the concentration of 10 microM had no effect on the maximal diastolic potential. MG8926 (10 microM) prolonged the cycle length, decreased the rate of diastolic depolarization, the rate of rise of action potential and tended to decrease the amplitude of action potential. MG8926 at the concentration of 10 microM had almost no effect on the maximal diastolic potential. The present findings may indicate that replacement of phenyl residue of prenylamine by cyclohexyl residue increases the inhibitory action on the slow Ca2+ channels in rabbit SA node.

  1. 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...

  2. 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.

  3. Making Class Actions Work: The Untapped Potential of the Internet

    Directory of Open Access Journals (Sweden)

    Robert H. Klonoff

    2008-04-01

    Full Text Available Over twenty years ago, the Supreme Court recognized that in class action litigation, absent class members “must receive notice plus an opportunity to be heard and participate in the litigation, whether in person or through counsel.” Although the absent class members’ rights to receive notice and an opportunity to opt out are of vital importance, the ability to be heard and participate in the litigation are also important.

  4. Dynamics of action potential initiation in the GABAergic thalamic reticular nucleus in vivo.

    Directory of Open Access Journals (Sweden)

    Fabián Muñoz

    Full Text Available 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.

  5. Face recognition memory across the adult life span: event-related potential evidence from the own-age bias.

    Science.gov (United States)

    Wolff, Nicole; Wiese, Holger; Schweinberger, Stefan R

    2012-12-01

    Young adult participants are more accurate at remembering young as compared with old faces (own-age bias). This study investigated behavioral and event-related potential (ERP) correlates of recognition memory in 4 consecutive age categories (ranging from 19-29, 30-44, 45-59, and 60-80 years), both with respect to face and participant age. Young and young middle-aged participants yielded more accurate recognition memory for both young and young middle-aged as compared to old middle-aged and old faces, suggesting that the own-age bias in adults is not exclusively directed toward age-congruent "in-group" faces. No own-age bias was observed in old middle-aged and elderly participants. Analysis of ERPs revealed significant positive correlations of both N170 latency and amplitude with participant age, thus, suggesting an age-related delay of processing speed and an increase in processing demands at early perceptual stages of face processing. Furthermore, an ERP old-new effect (400-700 ms), with more positive amplitudes for hits as compared with correct rejections, was detected in young and young middle-aged participants but not in the 2 older groups. Because these older groups did not demonstrate enhanced memory performance for own-age faces, we suggest that detailed recollection of study-episode information, as reflected in the ERP old-new effect, may be a necessary prerequisite for the own-age bias.

  6. Potential fitting biases resulting from grouping data into variable width bins

    CERN Document Server

    Towers, S

    2012-01-01

    When reading peer-reviewed scientific literature describing any analysis of empirical data, it is natural and correct to proceed with the underlying assumption that experiments have made good faith efforts to ensure that their analyses yield unbiased results. However, particle physics experiments are expensive and time consuming to carry out, thus if an analysis has inherent bias (even if unintentional), much money and effort can be wasted trying to replicate or understand the results, particularly if the analysis is fundamental to our understanding of the universe. In this note we discuss the significant biases that can result from data binning schemes. As we will show, if data are binned such that they provide the best comparison to a particular (but incorrect) model, the resulting model parameter estimates when fitting to the binned data can be significantly biased, leading us to too often accept the model hypothesis when it is not in fact true. When using binned likelihood or least squares methods there i...

  7. 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

    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...

  8. 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.

  9. Prolonged modification of action potential shape by synaptic inputs in molluscan neurones.

    Science.gov (United States)

    Winlow, W

    1985-01-01

    1. Somatic action potentials of Lymnaea neurons are modified by excitatory or inhibitory synaptic inputs and have been studied using phase-plane techniques and an action potential duration monitor. 2. Excitatory synaptic inputs increase the rate of neuronal discharge, cause action potential broadening, a decrease in the maximum rate of depolarization (Vd) and a decrease in the maximum rate of repolarization (Vr). 3. Inhibitory synaptic inputs decrease the discharge rate and cause narrowing of action potentials, an increase in Vd and an increase in Vr. 4. The effects reported above outlast the original synaptic inputs by many seconds and, if the somatic action potentials are similar to those in the axon terminals, they may have far-reaching effects on transmitter release.

  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

    Although oscillations in membrane potential are a prominent feature of sensory, motor, and cognitive function, their precise role in signal processing remains elusive. Here we show, using a combination of in vivo, in vitro, and theoretical approaches, that both synaptically and intrinsically......, membrane potential oscillations dramatically enhance the discriminatory capabilities of individual neurons and networks of cells and provide one attractive explanation for their abundance in neurophysiological systems....

  11. Genotoxic potential of glyphosate formulations: mode-of-action investigations.

    Science.gov (United States)

    Heydens, William F; Healy, Charles E; Hotz, Kathy J; Kier, Larry D; Martens, Mark A; Wilson, Alan G E; Farmer, Donna R

    2008-02-27

    A broad array of in vitro and in vivo assays has consistently demonstrated that glyphosate and glyphosate-containing herbicide formulations (GCHF) are not genotoxic. Occasionally, however, related and contradictory data are reported, including findings of mouse liver and kidney DNA adducts and damage following intraperitoneal (ip) injection. Mode-of-action investigations were therefore undertaken to determine the significance of these contradictory data while concurrently comparing results from ip and oral exposures. Exposure by ip injection indeed produced marked hepatic and renal toxicity, but oral administration did not. The results suggest that ip injection of GCHF may induce secondary effects mediated by local toxicity rather than genotoxicity. Furthermore, these results continue to support the conclusion that glyphosate and GCHF are not genotoxic under exposure conditions that are relevant to animals and humans.

  12. Potential synergy of phytochemicals in cancer prevention: mechanism of action.

    Science.gov (United States)

    Liu, Rui Hai

    2004-12-01

    Epidemiological studies have consistently shown that regular consumption of fruits and vegetables is strongly associated with reduced risk of developing chronic diseases, such as cancer and cardiovascular disease. It is now widely believed that the actions of the antioxidant nutrients alone do not explain the observed health benefits of diets rich in fruits and vegetables, because taken alone, the individual antioxidants studied in clinical trials do not appear to have consistent preventive effects. Work performed by our group and others has shown that fruits and vegetable phytochemical extracts exhibit strong antioxidant and antiproliferative activities and that the major part of total antioxidant activity is from the combination of phytochemicals. We proposed that the additive and synergistic effects of phytochemicals in fruits and vegetables are responsible for these potent antioxidant and anticancer activities and that the benefit of a diet rich in fruits and vegetables is attributed to the complex mixture of phytochemicals present in whole foods. This explains why no single antioxidant can replace the combination of natural phytochemicals in fruits and vegetables to achieve the health benefits. The evidence suggests that antioxidants or bioactive compounds are best acquired through whole-food consumption, not from expensive dietary supplements. We believe that a recommendation that consumers eat 5 to 10 servings of a wide variety of fruits and vegetables daily is an appropriate strategy for significantly reducing the risk of chronic diseases and to meet their nutrient requirements for optimum health.

  13. Gene networks activated by specific patterns of action potentials in dorsal root ganglia neurons

    Science.gov (United States)

    Lee, Philip R.; Cohen, Jonathan E.; Iacobas, Dumitru A.; Iacobas, Sanda; Fields, R. Douglas

    2017-01-01

    Gene regulatory networks underlie the long-term changes in cell specification, growth of synaptic connections, and adaptation that occur throughout neonatal and postnatal life. Here we show that the transcriptional response in neurons is exquisitely sensitive to the temporal nature of action potential firing patterns. Neurons were electrically stimulated with the same number of action potentials, but with different inter-burst intervals. We found that these subtle alterations in the timing of action potential firing differentially regulates hundreds of genes, across many functional categories, through the activation or repression of distinct transcriptional networks. Our results demonstrate that the transcriptional response in neurons to environmental stimuli, coded in the pattern of action potential firing, can be very sensitive to the temporal nature of action potential delivery rather than the intensity of stimulation or the total number of action potentials delivered. These data identify temporal kinetics of action potential firing as critical components regulating intracellular signalling pathways and gene expression in neurons to extracellular cues during early development and throughout life. PMID:28256583

  14. A fast, open source implementation of adaptive biasing potentials uncovers a ligand design strategy for the chromatin regulator BRD4

    Science.gov (United States)

    Dickson, Bradley M.; de Waal, Parker W.; Ramjan, Zachary H.; Xu, H. Eric; Rothbart, Scott B.

    2016-10-01

    In this communication we introduce an efficient implementation of adaptive biasing that greatly improves the speed of free energy computation in molecular dynamics simulations. We investigated the use of accelerated simulations to inform on compound design using a recently reported and clinically relevant inhibitor of the chromatin regulator BRD4 (bromodomain-containing protein 4). Benchmarking on our local compute cluster, our implementation achieves up to 2.5 times more force calls per day than plumed2. Results of five 1 μs-long simulations are presented, which reveal a conformational switch in the BRD4 inhibitor between a binding competent and incompetent state. Stabilization of the switch led to a -3 kcal/mol improvement of absolute binding free energy. These studies suggest an unexplored ligand design principle and offer new actionable hypotheses for medicinal chemistry efforts against this druggable epigenetic target class.

  15. A fast, open source implementation of adaptive biasing potentials uncovers a ligand design strategy for the chromatin regulator BRD4

    CERN Document Server

    Dickson, Bradley M; Ramjan, Zachary H; Xu, H Eric; Rothbart, Scott B

    2016-01-01

    In this communication we introduce an efficient implementation of adaptive biasing that greatly improves the speed of free energy computation in molecular dynamics simulations. We investigated the use of accelerated simulations to inform on compound design using a recently reported and clinically relevant inhibitor of the chromatin regulator BRD4. Benchmarking on our local compute cluster, our implementation achieves up to 2.5 times more force calls per day than plumed2. Results of five 1{\\mu}second-long simulations are presented, which reveal a conformational switch in the BRD4 inhibitor between a binding competent and incompetent state. Stabilization of the switch led to a -3 kcal/mol improvement of absolute binding free energy. These studies suggest an unexplored ligand design principle and offer new actionable hypotheses for medicinal chemistry efforts against this druggable epigenetic target class.

  16. Social identity-based motivation modulates attention bias toward negative information: an event-related brain potential study.

    Science.gov (United States)

    Montalan, Benoît; Boitout, Alexis; Veujoz, Mathieu; Leleu, Arnaud; Germain, Raymonde; Personnaz, Bernard; Lalonde, Robert; Rebaï, Mohamed

    2011-01-01

    Research has demonstrated that people readily pay more attention to negative than to positive and/or neutral stimuli. However, evidence from recent studies indicated that such an attention bias to negative information is not obligatory but sensitive to various factors. Two experiments using intergroup evaluative tasks (Study 1: a gender-related groups evaluative task and Study 2: a minimal-related groups evaluative task) was conducted to determine whether motivation to strive for a positive social identity - a part of one's self-concept - drives attention toward affective stimuli. Using the P1 component of event-related brain potentials (ERPs) as a neural index of attention, we confirmed that attention bias toward negative stimuli is not mandatory but it can depend on a motivational focus on affective outcomes. Results showed that social identity-based motivation is likely to bias attention toward affectively incongruent information. Thereby, early onset processes - reflected by the P1 component - appeared susceptible to top-down attentional influences induced by the individual's motivation to strive for a positive social identity.

  17. Alterations in nerve and muscle compound action potentials after acute acrylamide administration.

    OpenAIRE

    Anderson, R. J.

    1982-01-01

    The early deficits of neurotoxicity induced by acrylamide were examined in rats by comparing nerve and muscle action potentials before and 24 hr after exposure to acrylamide (25, 50 or 100 mg/kg). No changes were seen in the nerve action potential amplitude or duration. The 25 mg/kg dose produced a more variable nerve conduction velocity. There was also a significant broadening of the muscle compound action potential. Neither of these effects were seen in the fasted controls. However, the len...

  18. Heuristic and analytic processes in reasoning: an event-related potential study of belief bias.

    Science.gov (United States)

    Banks, Adrian P; Hope, Christopher

    2014-03-01

    Human reasoning involves both heuristic and analytic processes. This study of belief bias in relational reasoning investigated whether the two processes occur serially or in parallel. Participants evaluated the validity of problems in which the conclusions were either logically valid or invalid and either believable or unbelievable. Problems in which the conclusions presented a conflict between the logically valid response and the believable response elicited a more positive P3 than problems in which there was no conflict. This shows that P3 is influenced by the interaction of belief and logic rather than either of these factors on its own. These findings indicate that belief and logic influence reasoning at the same time, supporting models in which belief-based and logical evaluations occur in parallel but not theories in which belief-based heuristic evaluations precede logical analysis.

  19. North African Influences and Potential Bias in Case-Control Association Studies in the Spanish Population

    Science.gov (United States)

    Pino-Yanes, María; Corrales, Almudena; Basaldúa, Santiago; Hernández, Alexis; Guerra, Luisa; Villar, Jesús; Flores, Carlos

    2011-01-01

    Background Despite the limited genetic heterogeneity of Spanish populations, substantial evidences support that historical African influences have not affected them uniformly. Accounting for such population differences might be essential to reduce spurious results in association studies of genetic factors with disease. Using ancestry informative markers (AIMs), we aimed to measure the African influences in Spanish populations and to explore whether these might introduce statistical bias in population-based association studies. Methodology/Principal Findings We genotyped 93 AIMs in Spanish (from the Canary Islands and the Iberian Peninsula) and Northwest Africans, and conducted population and individual-based clustering analyses along with reference data from the HapMap, HGDP-CEPH, and other sources. We found significant differences for the Northwest African influence among Spanish populations from as low as ≈5% in Spanish from the Iberian Peninsula to as much as ≈17% in Canary Islanders, whereas the sub-Saharan African influence was negligible. Strikingly, the Northwest African ancestry showed a wide inter-individual variation in Canary Islanders ranging from 0% to 96%, reflecting the violent way the Islands were conquered and colonized by the Spanish in the XV century. As a consequence, a comparison of allele frequencies between Spanish samples from the Iberian Peninsula and the Canary Islands evidenced an excess of markers with significant differences. However, the inflation of p-values for the differences was adequately controlled by correcting for genetic ancestry estimates derived from a reduced number of AIMs. Conclusions/Significance Although the African influences estimated might be biased due to marker ascertainment, these results confirm that Northwest African genetic footprints are recognizable nowadays in the Spanish populations, particularly in Canary Islanders, and that the uneven African influences existing in these populations might increase the

  20. North African influences and potential bias in case-control association studies in the Spanish population.

    Directory of Open Access Journals (Sweden)

    María Pino-Yanes

    Full Text Available BACKGROUND: Despite the limited genetic heterogeneity of Spanish populations, substantial evidences support that historical African influences have not affected them uniformly. Accounting for such population differences might be essential to reduce spurious results in association studies of genetic factors with disease. Using ancestry informative markers (AIMs, we aimed to measure the African influences in Spanish populations and to explore whether these might introduce statistical bias in population-based association studies. METHODOLOGY/PRINCIPAL FINDINGS: We genotyped 93 AIMs in Spanish (from the Canary Islands and the Iberian Peninsula and Northwest Africans, and conducted population and individual-based clustering analyses along with reference data from the HapMap, HGDP-CEPH, and other sources. We found significant differences for the Northwest African influence among Spanish populations from as low as ≈ 5% in Spanish from the Iberian Peninsula to as much as ≈ 17% in Canary Islanders, whereas the sub-Saharan African influence was negligible. Strikingly, the Northwest African ancestry showed a wide inter-individual variation in Canary Islanders ranging from 0% to 96%, reflecting the violent way the Islands were conquered and colonized by the Spanish in the XV century. As a consequence, a comparison of allele frequencies between Spanish samples from the Iberian Peninsula and the Canary Islands evidenced an excess of markers with significant differences. However, the inflation of p-values for the differences was adequately controlled by correcting for genetic ancestry estimates derived from a reduced number of AIMs. CONCLUSIONS/SIGNIFICANCE: Although the African influences estimated might be biased due to marker ascertainment, these results confirm that Northwest African genetic footprints are recognizable nowadays in the Spanish populations, particularly in Canary Islanders, and that the uneven African influences existing in these

  1. Potential sources of bias in the use of Escherichia coli to measure waterborne diarrhoea risk in low-income settings.

    Science.gov (United States)

    Ercumen, Ayse; Arnold, Benjamin F; Naser, Abu Mohd; Unicomb, Leanne; Colford, John M; Luby, Stephen P

    2017-01-01

    Escherichia coli is the standard water quality indicator for diarrhoea risk. Yet, the association between E. coli and diarrhoea is inconsistent across studies without a systematic assessment of methodological differences behind this variation. Most studies measure water quality cross-sectionally with diarrhoea, risking exposure misclassification and reverse causation. Studies use different recall windows for self-reported diarrhoea; longer periods increase potential outcome misclassification through misrecall. Control of confounding is inconsistent across studies. Additionally, diarrhoea measured in unblinded intervention trials can present courtesy bias. We utilised measurements from a randomised trial of water interventions in Bangladesh to assess how these factors affect the E. coli-diarrhoea association. We compared cross-sectional versus prospective measurements of water quality and diarrhoea, 2-versus 7-day symptom recall periods, estimates with and without controlling for confounding and using measurements from control versus intervention arms of the trial. In the control arm, 2-day diarrhoea prevalence, measured prospectively 1 month after water quality, significantly increased with log10 E. coli (PR = 1.50, 1.02-2.20). This association weakened when we used 7-day recall (PR = 1.18, 0.88-1.57), cross-sectional measurements of E. coli and diarrhoea (PR = 1.11, 0.79-1.56) or did not control for confounding (PR = 1.20, 0.88-1.62). Including data from intervention arms led to less interpretable associations, potentially due to courtesy bias, effect modification and/or reverse causation. By systematically addressing potential sources of bias, our analysis demonstrates a clear relationship between E. coli in drinking water and diarrhoea, suggesting that the continued use of E. coli as an indicator of waterborne diarrhoea risk is justified. © 2016 John Wiley & Sons Ltd.

  2. Antioxidant properties of melatonin and its potential action in diseases.

    Science.gov (United States)

    Karaaslan, Cigdem; Suzen, Sibel

    2015-01-01

    In recent years, relationship between free radicals and oxidative stress with aging, cancer, atherosclerosis, neurodegenerative disorders, diabetes, and inflammatory diseases became increasingly clear. Confirming the role of oxidants in numerous pathological conditions such as cancer, the antioxidants developed as therapeutics have been proven ineffective. It is well established that melatonin (MLT) and its metabolites are able to function as endogenous free-radical scavengers and broadspectrum antioxidants. Numerous studies also proved the role of MLT and its derivatives in many physiological processes and therapeutic functions, such as the regulation of circadian rhythm and immune functions. The aim of this review is to arouse attention to MLT as a potentially valuable agent in the prevention and/or treatment of some diseases.

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

    Science.gov (United States)

    Sengupta, Biswa; Laughlin, Simon Barry; Niven, Jeremy Edward

    2014-01-01

    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.

  4. Molecular model of the action potential sodium channel.

    Science.gov (United States)

    Guy, H R; Seetharamulu, P

    1986-01-01

    Secondary and tertiary structural models of sodium channel transmembrane segments were developed from its recently determined primary sequence in Electrophorus electricus. The model has four homologous domains, and each domain has eight homologous transmembrane segments, S1 through S8. Each domain contains three relatively apolar segments (S1, S2 and S3) and two very apolar segments (S5 and S8), all postulated to be transmembrane alpha-helices. S4 segments have positively charged residues, mainly arginines, at every third residue. The model channel lining is formed by four S4 transmembrane alpha-helices and four negatively charged S7 segments. S7 segments are postulated to be short, partially transmembrane amphipathic alpha-helices in three domains and a beta-strand in the last domain. S7 segments are preceded by short apolar segments (S6) postulated to be alpha-helices in three domains and a beta-strand in the last domain. Positively charged side chains of S4 form salt bridges with negatively charged side chains on S7 and near the ends of S1 and S3. Putative extracellular segments that contain 5 of the 10 potential N-glycosylation sites link S5 to S6. Channel activation may involve a 'helical screw' mechanism in which S4 helices rotate around their axes as they move toward the extracellular surface. Images PMID:2417247

  5. 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...

  6. 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...

  7. Axon initial segment Kv1 channels control axonal action potential waveform and synaptic efficacy.

    Science.gov (United States)

    Kole, Maarten H P; Letzkus, Johannes J; Stuart, Greg J

    2007-08-16

    Action potentials are binary signals that transmit information via their rate and temporal pattern. In this context, the axon is thought of as a transmission line, devoid of a role in neuronal computation. Here, we show a highly localized role of axonal Kv1 potassium channels in shaping the action potential waveform in the axon initial segment (AIS) of layer 5 pyramidal neurons independent of the soma. Cell-attached recordings revealed a 10-fold increase in Kv1 channel density over the first 50 microm of the AIS. Inactivation of AIS and proximal axonal Kv1 channels, as occurs during slow subthreshold somatodendritic depolarizations, led to a distance-dependent broadening of axonal action potentials, as well as an increase in synaptic strength at proximal axonal terminals. Thus, Kv1 channels are strategically positioned to integrate slow subthreshold signals, providing control of the presynaptic action potential waveform and synaptic coupling in local cortical circuits.

  8. Control of Secretion by Encodes of Action Potentials in Neuronal Cells

    Institute of Scientific and Technical Information of China (English)

    Kailai Duan; Zhuan Zhou

    2003-01-01

    @@ Action potentials (APs) are principle physiological stimuli of neurotransmitter secretion or synaptic transmis sion. Most studies on stimulus-secretion-coupling have been performed under voltage clamp using artificial electric stimulations.

  9. Action potential broadening and frequency-dependent facilitation of calcium signals in pituitary nerve terminals.

    Science.gov (United States)

    Jackson, M B; Konnerth, A; Augustine, G J

    1991-01-15

    Hormone release from nerve terminals in the neurohypophysis is a sensitive function of action potential frequency. We have investigated the cellular mechanisms responsible for this frequency-dependent facilitation by combining patch clamp and fluorimetric Ca2+ measurements in single neurosecretory terminals in thin slices of the rat posterior pituitary. In these terminals both action potential-induced changes in the intracellular Ca2+ concentration ([Ca2+]i) and action potential duration were enhanced by high-frequency stimuli, all with a frequency dependence similar to that of hormone release. Furthermore, brief voltage clamp pulses inactivated a K+ current with a very similar frequency dependence. These results support a model for frequency-dependent facilitation in which the inactivation of a K+ current broadens action potentials, leading to an enhancement of [Ca2+]i signals. Further experiments tested for a causal relationship between action potential broadening and facilitation of [Ca2+]i changes. First, increasing the duration of depolarization, either by broadening action potentials with the K(+)-channel blocker tetraethylammonium or by applying longer depolarizing voltage clamp steps, increased [Ca2+]i changes. Second, eliminating frequency-dependent changes in duration, by voltage clamping the terminal with constant duration pulses, substantially reduced the frequency-dependent enhancement of [Ca2+]i changes. These results indicate that action potential broadening contributes to frequency-dependent facilitation of [Ca2+]i changes. However, the small residual frequency dependence of [Ca2+]i changes seen with constant duration stimulation suggests that a second process, distinct from action potential broadening, also contributes to facilitation. These two frequency-dependent mechanisms may also contribute to activity-dependent plasticity in synaptic terminals.

  10. Uniform Action Potential Repolarization within the Sarcolemma of In Situ Ventricular Cardiomyocytes

    OpenAIRE

    Bu, Guixue; Adams, Heather; Berbari, Edward J.; Rubart, Michael

    2009-01-01

    Previous studies have speculated, based on indirect evidence, that the action potential at the transverse (t)-tubules is longer than at the surface membrane in mammalian ventricular cardiomyocytes. To date, no technique has enabled recording of electrical activity selectively at the t-tubules to directly examine this hypothesis. We used confocal line-scan imaging in conjunction with the fast response voltage-sensitive dyes ANNINE-6 and ANNINE-6plus to resolve action potential-related changes ...

  11. Epidermal Laser Stimulation of Action Potentials in the Frog Sciatic Nerve

    Science.gov (United States)

    2008-10-01

    Laser Stimulation of Action Potentials in the Frog Sciatic Nerve Nichole M. Jindra Robert J. Thomas Human Effectiveness Directorate Directed...in the Frog Sciatic Nerve 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 62202F 6. AUTHOR(S) .Nichole M. Jindra, Robert J. Thomas, Douglas N...Alan Rice 14. ABSTRACT Measurements of laser stimulated action potentials in the sciatic nerve of leopard frogs (Rana pipiens) were made using

  12. UNAIDS ‘multiple sexual partners’ core indicator: promoting sexual networks to reduce potential biases

    Directory of Open Access Journals (Sweden)

    Zacharie Tsala Dimbuene

    2014-03-01

    Full Text Available UNAIDS proposed a set of core indicators for monitoring changes in the worldwide AIDS epidemic. This paper explores the validity and effectiveness of the ‘multiple sexual partners’ core indicator, which is only partially captured with current available data. The paper also suggests an innovative approach for collecting more informative data that can be used to provide an accurate measure of the UNAIDS's ‘multiple sexual partners’ core indicator. Specifically, the paper addresses three major limitations associated with the indicator when it is measured with respondents’ sexual behaviors. First, the indicator assumes that a person's risk of contracting HIV/AIDS/STIs is merely a function of his/her own sexual behavior. Second, the indicator does not account for a partner's sexual history, which is very important in assessing an individual's risk level. Finally, the 12-month period used to define a person's risks can be misleading, especially because HIV/AIDS theoretically has a period of latency longer than a year. The paper concludes that, programmatically, improvements in data collection are a top priority for reducing the observed bias in the ‘multiple sexual partners’ core indicator.

  13. Meiotic crossover control by concerted action of Rad51-Dmc1 in homolog template bias and robust homeostatic regulation.

    Directory of Open Access Journals (Sweden)

    Jessica P Lao

    Full Text Available During meiosis, repair of programmed DNA double-strand breaks (DSBs by recombination promotes pairing of homologous chromosomes and their connection by crossovers. Two DNA strand-exchange proteins, Rad51 and Dmc1, are required for meiotic recombination in many organisms. Studies in budding yeast imply that Rad51 acts to regulate Dmc1's strand exchange activity, while its own exchange activity is inhibited. However, in a dmc1 mutant, elimination of inhibitory factor, Hed1, activates Rad51's strand exchange activity and results in high levels of recombination without participation of Dmc1. Here we show that Rad51-mediated meiotic recombination is not subject to regulatory processes associated with high-fidelity chromosome segregation. These include homolog bias, a process that directs strand exchange between homologs rather than sister chromatids. Furthermore, activation of Rad51 does not effectively substitute for Dmc1's chromosome pairing activity, nor does it ensure formation of the obligate crossovers required for accurate homolog segregation. We further show that Dmc1's dominance in promoting strand exchange between homologs involves repression of Rad51's strand-exchange activity. This function of Dmc1 is independent of Hed1, but requires the meiotic kinase, Mek1. Hed1 makes a relatively minor contribution to homolog bias, but nonetheless this is important for normal morphogenesis of synaptonemal complexes and efficient crossing-over especially when DSB numbers are decreased. Super-resolution microscopy shows that Dmc1 also acts to organize discrete complexes of a Mek1 partner protein, Red1, into clusters along lateral elements of synaptonemal complexes; this activity may also contribute to homolog bias. Finally, we show that when interhomolog bias is defective, recombination is buffered by two feedback processes, one that increases the fraction of events that yields crossovers, and a second that we propose involves additional DSB formation

  14. Variations in retrieval monitoring during action memory judgments: evidence from event-related potentials (ERPs).

    Science.gov (United States)

    Leynes, P Andrew; Kakadia, Bhavika

    2013-02-01

    The present study investigated the neuroscience of memory for actions using event-related potentials (ERPs). Actions were performed, initiated but not completed (i.e., interrupted), or watched while the experimenter performed the action during encoding. Memory was assessed in a reality monitoring (RM) test (performed vs. watched actions), as well as in an internal source monitoring (ISM) test (performed vs. interrupted) while ERPs were recorded. Behavioral measures provided evidence of robust old/new recognition for all actions, but the analysis of source errors revealed that interrupted actions were often confused with performed actions. The ERP correlate of recollection, the parietal "old/new" effect (700-900ms), was observed for all actions. The right frontal "old/new" effect (1500-1800ms) that correlates with general memory monitoring was observed in RM but not in ISM. Instead, ISM was associated with the late posterior negativity (LPN) that has been connected to more specific memory monitoring. This pattern of ERP findings suggest that, in this context, general monitoring was used to discriminate self- versus other-performed actions, whereas more specific monitoring was required to support the discrimination of completed and interrupted actions. We argue that the mix of general/specific monitoring processes is shaped by the global retrieval context, which includes the number of memory features that overlap and the combination of sources being considered among other factors.

  15. 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....

  16. Potential Bias in Projecting Future Regional Megadrought Risk: Insights From A Global Data-Model Framework

    Science.gov (United States)

    Overpeck, J. T.; Ault, T.; Cole, J. E.; Fasullo, J.; Loope, G. R.; Parsons, L. A.; Stevenson, S.

    2015-12-01

    Megadrought is one of the most significant and costly climate extremes, and one that stakeholders (e.g., water and other resource managers) the world over wish to understand better; in particular, they need estimates of the risk of severe droughts as a function of drought frequency, severity, duration, and atmospheric greenhouse gas concentration. In many dry-climate regions of the globe, megadrought is synonymous with multi-decadal drought. However, in other regions, megadrought can be defined as extended drought, mostly not seen in the period of instrumental observations, and that would have large impacts if it were to occur in the future. New and published paleoclimatic observations allow us to understand the spectrum of drought in many regions of the globe; droughts exceeding 50 years have occurred in recent Earth history in southwestern North America, sub-Saharan Africa, the Mediterranean and Australia, whereas shorter megadroughts have occurred in Monsoon Asia, Amazonia and elsewhere. Data-model comparisons for regions with sufficiently long (e.g., 1000-2000 years) records of observed hydroclimatic variability suggest that state-of-the-art models can provide realistic estimates of interannual to decadal drought risk, but underestimate the risk of megadrought. Likely reasons for this shortcoming are the lack of sufficient multi-decadal variability in simulations of the past and future, plus an underappreciated understanding about how temperature variability and land-surface feedbacks interact with hydrological and ecological drought, as well as the roles played by unusually wet hydroclimatic extremes (e.g., ENSO related) in ending droughts of long duration. Paleoclimatic records also provide the opportunity to estimate how much models underestimate megadrought risk as a function of locale, frequency, severity, duration, and atmospheric greenhouse gas concentration; they also aid in providing stakeholders with bias-corrected estimates of megadrought risk.

  17. Biased Motion in a Symmetric Periodic Potential by Breaking Temporal Symmetry

    Institute of Scientific and Technical Information of China (English)

    ZHENG Zhi-Gang; LI Xiao-Wen

    2001-01-01

    Unidirectional transport of a particle in a spatially periodic and symmetric potential under a periodic force with broken temporal symmetry is studied. With a collaboration of the potential field and the asymmetric ac force, a dc current can be observed. Resonant current steps are found for a finite period of the ac force. A phase diagram of these resonant steps is given. Stochastic-resonance-like directional transport induced by thermal noises is revealed.

  18. Pulsed magnetic stimulation modifies amplitude of action potentials in vitro via ionic channels-dependent mechanism.

    Science.gov (United States)

    Ahmed, Zaghloul; Wieraszko, Andrzej

    2015-07-01

    This paper investigates the influence of pulsed magnetic fields (PMFs) on amplitude of evoked, compound action potential (CAP) recorded from the segments of sciatic nerve in vitro. PMFs were applied for 30 min at frequency of 0.16 Hz and intensity of 15 mT. In confirmation of our previous reports, PMF exposure enhanced amplitude of CAPs. The effect persisted beyond PMF activation period. As expected, CAP amplitude was attenuated by antagonists of sodium channel, lidocaine, and tetrodotoxin. Depression of the potential by sodium channels antagonists was reversed by subsequent exposure to PMFs. The effect of elevated potassium concentration and veratridine on the action potential was modified by exposure to PMFs as well. Neither inhibitors of protein kinase C and protein kinase A, nor known free radicals scavengers had any effects on PMF action. Possible mechanisms of PMF action are discussed.

  19. Action-space clustering of tidal streams to infer the Galactic potential

    CERN Document Server

    Sanderson, Robyn E; Hogg, David W

    2014-01-01

    We present a new method for constraining the Milky Way halo gravitational potential by simultaneously fitting multiple tidal streams. This method requires full three-dimensional positions and velocities for all stars in the streams, but does not require identification of any specific stream, nor determination of stream membership for any star. We exploit the principle that the action distribution of stream stars is most clustered---that is, most informative---when the potential used to calculate the actions is closest to the true potential. We measure the amount of clustering with the Kullback-Leibler Divergence (KLD) or relative entropy, a statistical measure of information which also provides uncertainties for our parameter estimates. We show, for toy Gaia-like data in a spherical isochrone potential, that maximizing the KLD of the action distribution relative to a smoother distribution recovers the true values of the potential parameters. The precision depends on the observational errors and the number and...

  20. Fishery induces sperm depletion and reduction in male reproductive potential for crab species under male-biased harvest strategy.

    Directory of Open Access Journals (Sweden)

    Luis Miguel Pardo

    Full Text Available Sperm depletion in males can occur when polygynous species are intensively exploited under a male-biased management strategy. In fisheries involving crabs species, the effects of this type of management on the reproductive potential is far from being understood. This study tests whether male-biased management of the principal Chilean crab fishery is able to affect the potential capacity of Metacarcinus edwardsii males to transfer sperm to females. Five localities in southern Chile, recording contrasting crab fishery landing, were selected to assess the potential of sperm depletion triggered by fishery. Seasonally, male crabs from each locality were obtained. Dry weight and histological condition of vasa deferentia and the Vaso-Somatic Index (VSI were determined in order to use them as proxies for sperm depletion and male reproductive condition. A manipulative experiment was performed in the laboratory to estimate vasa deferentia weight and VSI from just-mated males in order to obtain a reference point for the potential effects of the fishery on sperm reserves. Sperm storage capacity is significantly affected by fisheries; during the mating season vasa deferentia from localities with low fishery intensity were heavier than those from high intensity fisheries, and these differences were even more evident in large males. Histological section showed that this disparity in vasa deferentia weight was explained principally by differences in the quantity of spermatophores rather than other seminal material. VSI was always higher in males from localities with low fishery intensity. Males from localities with high fishery intensity showed little capacity to recover sperm reserves and the VSI of these males remained below the values of the just-mated males. Detriment in the capacity of males to transfer sperm is the first step to sperm limitation in an exploited population, thus detection of sperm depletion can be an alert to introduce changes in the

  1. Preoperative Breast MRI: Surgeons' Patient Selection Patterns and Potential Bias in Outcomes Analyses.

    Science.gov (United States)

    Lee, Jiyon; Tanaka, Elaine; Eby, Peter R; Zhou, Shouhao; Wei, Wei; Eppelheimer, Christine; Loving, Vilert A

    2017-04-01

    = 0.01) and tumors smaller than 1 cm (mean Likert score, 3.84 vs 3.40; p = 0.002). Breast surgeons referred less often than did general surgeons for multifocal or multicentric disease (mean Likert score, 5.02 vs 5.44; p = 0.001). Breast surgeons and general surgeons similarly weighed other variables. Preoperative breast MRI referral trended with certain higher risk patient- and tumor-related and clinical variables and were nonuniform between the breast surgeons and general surgeon cohorts. Selection bias could affect outcomes analyses for preoperative breast MRI.

  2. Financial conflicts of interest in plastic surgery: background, potential for bias, disclosure, and transparency.

    Science.gov (United States)

    Luce, Edward A

    2015-04-01

    Relationships between physicians and industry, whether it be pharmaceutical companies, medical device manufacturers, or purveyors of medical technology, contain both an element of potential for good and a potential for harm. Certainly, the potential for good is realized when the collaboration results in improved plastic surgery patient care due to product and technology development. If the collaboration contains a financial component, the potential for harm exists in the form of a financial conflict of interest on the part of the physician. Recently, considerable discussion has been directed toward the pervasiveness of financial conflict of interest in all three arenas of the profession of medicine: education, research, and clinical practice, although an overlap exists among all three with respect to the issue of conflict of interest. This article will focus on conflict of interest in plastic surgery education, both continuing medical education for practitioners and graduate medical education for plastic surgery residents, as well as conflict of interest in research, such as conflicts related to publications in our literature.

  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.

  4. Bepridil (CERM-1978) blockade of action potentials in cultured rat aortic smooth muscle cells.

    Science.gov (United States)

    Mras, S; Sperelakis, N

    1981-04-24

    Reaggregate cultures (primary) were prepared from enzyme-dispersed vascular smooth muscle (VSM) cells from rat aortas. The cultures were incubated for 7-10 days, and then studied by the intracellular microelectrode technique. The cells were electrically quiescent (mean resting potential of --47 mV), and extracellular electrical stimulation usually did not elicit a membrane response. Addition of 10 mM tetraethylammonium rapidly induced excitability, allowing the VSM cells to fire Ca2+-dependent action potentials in response to electrical stimulation. The electrical responses often had two components, an initial spike and a later plateau-like component. The action potential spikes had a mean amplitude of 22 mV but occasionally were overshooting; the plateaus had a mean duration (at 50% repolarization) of 3.8 sec. A new anti-anginal agent, bepridil (10(-8)-10(-5) M), depressed the amplitude and duration of the plateau and blocked the spike component of the action potential in a dose-dependent fashion without affecting the resting potential. This finding is consistent with the view that bepridil acts as a Ca2+-antagonistic agent to prevent the generation of the action potentials, and this action can explain its antianginal properties.

  5. Effects of acetylcholine and noradrenalin on action potentials of isolated rabbit sinoatrial and atrial myocytes

    Directory of Open Access Journals (Sweden)

    Arie O. Verkerk

    2012-05-01

    Full Text Available The autonomic nervous system controls heart rate and contractility through sympathetic and parasympathetic inputs to the cardiac tissue, with acetylcholine (ACh and noradrenalin (NA as the chemical transmitters. In recent years, it has become clear that specific Regulators of G protein Signalling proteins (RGS proteins suppress muscarinic sensitivity and parasympathetic tone, identifying RGS proteins as intriguing potential therapeutic targets. In the present study, we have identified the effects of 1 µM ACh and 1 µM NA on the intrinsic action potentials of sinotrial (SA nodal and atrial myocytes. Single cells were enzymatically isolated from the SA node or from the left atrium of rabbit hearts. Action potentials were recorded using the amphotericin-perforated patch-clamp technique in the absence and presence of ACh, NA or a combination of both. In SA nodal myocytes, ACh increased cycle length and decreased diastolic depolarization rate, whereas NA decreased cycle length and increased diastolic depolarization rate. Both ACh and NA increased maximum upstroke velocity. Furthermore, ACh hyperpolarized the maximum diastolic potential. In atrial myocytes stimulated at 2 Hz, both ACh and NA hyperpolarized the maximum diastolic potential, increased the action potential amplitude, and increased the maximum upstroke velocity. Action potential duration at 50 and 90% repolarization was decreased by ACh, but increased by NA. The effects of both ACh and NA on action potential duration showed a dose dependence in the range of 1–1,000 nM, while a clear-cut frequency dependence in the range of 1–4 Hz was absent. Intermediate results were obtained in the combined presence of ACh and NA in both SA nodal and atrial myocytes. Our data uncover the extent to which SA nodal and atrial action potentials are intrinsically dependent on ACh, NA or a combination of both and may thus guide further experiments with RGS proteins.

  6. Frequency-dependent action potential prolongation in Aplysia pleural sensory neurones.

    Science.gov (United States)

    Edstrom, J P; Lukowiak, K D

    1985-10-01

    The effects of repetitive activity on action-potential shape in Aplysia californica pleural sensory cells are described. Action potentials were evoked by intracellular current injection at frequencies between 7.41 and 0.2 Hz. In contrast to other molluscan neurons having brief action potentials, it was found that at these firing rates the normally brief action potential develops a prominent shoulder or plateau during the repolarization phase. Higher stimulus rates broaden the action potential more rapidly and to a greater extent than lower stimulus rates. Inactivation is slow relative to activation; effects of 3-s 6-Hz trains are detectable after 1 min rest. The amplitude of the plateau voltage reaches a maximum of 50-70 mV at the highest stimulus rates tested. Frequency-dependent increases in action-potential duration measured at half-amplitude normally range between 6 and 15 ms. Cadmium, at concentrations between 0.05 and 0.5 mM, antagonizes frequency-dependent broadening. The increases in duration induced by repetitive activity are more sensitive to cadmium than are the increases in plateau amplitude. Tetraethylammonium, at concentrations between 0.5 and 10 mM, slightly increases the duration and amplitude of single action potentials. During repetitive activity at high stimulus rates the maximum duration and rate of broadening are both increased but the amplitude of the plateau potential is not affected by these tetraethylammonium concentrations. Above 10 mM, tetraethylammonium greatly increases the duration and amplitude of single action potentials as well as the rates of action-potential duration and amplitude increase during repetitive activity. These high tetraethylammonium concentrations also cause the normally smoothly increasing duration and amplitude to reach a maximum value early in a train and then decline slowly during the remainder of the train. The consequences of frequency-dependent spike broadening in these neurons have not yet been investigated

  7. Bias driven coherent carrier dynamics in a two-dimensional aperiodic potential

    NARCIS (Netherlands)

    de Moura, F. A. B. F.; Viana, L. P.; Lyra, M. L.; Malyshev, Victor; Dominguez-Adame, F.

    2008-01-01

    We study the dynamics of an electron wave-packet in a two-dimensional square lattice with an aperiodic site potential in the presence of an external uniform electric field. The aperiodicity is described by epsilon(m) = V cos(pi alpha m(x)(nu x)) cos(pi alpha m(y)(nu y)) at lattice sites (m(x),m(y)),

  8. 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.

  9. Sodium and calcium currents shape action potentials in immature mouse inner hair cells.

    Science.gov (United States)

    Marcotti, Walter; Johnson, Stuart L; Rusch, Alfons; Kros, Corne J

    2003-11-01

    Before the onset of hearing at postnatal day 12, mouse inner hair cells (IHCs) produce spontaneous and evoked action potentials. These spikes are likely to induce neurotransmitter release onto auditory nerve fibres. Since immature IHCs express both alpha1D (Cav1.3) Ca2+ and Na+ currents that activate near the resting potential, we examined whether these two conductances are involved in shaping the action potentials. Both had extremely rapid activation kinetics, followed by fast and complete voltage-dependent inactivation for the Na+ current, and slower, partially Ca2+-dependent inactivation for the Ca2+ current. Only the Ca2+ current is necessary for spontaneous and induced action potentials, and 29 % of cells lacked a Na+ current. The Na+ current does, however, shorten the time to reach the action-potential threshold, whereas the Ca2+ current is mainly involved, together with the K+ currents, in determining the speed and size of the spikes. Both currents increased in size up to the end of the first postnatal week. After this, the Ca2+ current reduced to about 30 % of its maximum size and persisted in mature IHCs. The Na+ current was downregulated around the onset of hearing, when the spiking is also known to disappear. Although the Na+ current was observed as early as embryonic day 16.5, its role in action-potential generation was only evident from just after birth, when the resting membrane potential became sufficiently negative to remove a sizeable fraction of the inactivation (half inactivation was at -71 mV). The size of both currents was positively correlated with the developmental change in action-potential frequency.

  10. The potential of the effective Polyakov line action from the underlying lattice gauge theory

    CERN Document Server

    Greensite, Jeff

    2012-01-01

    I adapt a numerical method, previously applied to investigate the Yang-Mills vacuum wavefunctional, to the problem of extracting the effective Polyakov line action from SU(N) lattice gauge theories, with or without matter fields. The method can be used to find the variation of the effective Polyakov line action along any trajectory in field configuration space; this information is sufficient to determine the potential term in the action, and strongly constrains the possible form of the kinetic term. The technique is illustrated for both pure and gauge-Higgs SU(2) lattice gauge theory at finite temperature. A surprise, in the pure gauge theory, is that the potential of the corresponding Polyakov line action contains a non-analytic (yet center-symmetric) term proportional to |P|^3, where P is the trace of the Polyakov line at a given point, in addition to the expected analytic terms proportional to even powers of P.

  11. Unmyelinated visceral afferents exhibit frequency dependent action potential broadening while myelinated visceral afferents do not.

    Science.gov (United States)

    Li, Bai-Yan; Feng, Bin; Tsu, Hwa Y; Schild, John H

    2007-06-21

    Sensory information arising from visceral organ systems is encoded into action potential trains that propagate along afferent fibers to target nuclei in the central nervous system. These information streams range from tight patterns of action potentials that are well synchronized with the sensory transduction event to irregular, patternless discharge with no clear correlation to the sensory input. In general terms these afferent pathways can be divided into unmyelinated and myelinated fiber types. Our laboratory has a long standing interest in the functional differences between these two types of afferents in terms of the preprocessing of sensory information into action potential trains (synchrony, frequency, duration, etc.), the reflexogenic consequences of this sensory input to the central nervous system and the ionic channels that give rise to the electrophysiological properties of these unique cell types. The aim of this study was to determine whether there were any functional differences in the somatic action potential characteristics of unmyelinated and myelinated vagal afferents in response to different rates of sensory nerve stimulation. Our results showed that activity and frequency-dependent widening of the somatic action potential was quite prominent in unmyelinated but not myelinated vagal afferents. Spike broadening often leads to increased influx of Ca(2+) ions that has been associated with a diverse range of modulatory mechanisms both at the cell body and central synaptic terminations (e.g. increased neurotransmitter release.) We conclude that our observations are indicative of fundamentally different mechanisms for neural integration of sensory information arising from unmyelinated and myelinated vagal afferents.

  12. How experience shapes memory for faces: an event-related potential study on the own-age bias.

    Science.gov (United States)

    Wiese, Holger; Wolff, Nicole; Steffens, Melanie C; Schweinberger, Stefan R

    2013-10-01

    Young adults more accurately remember own-age than older faces. We tested whether this own-age bias (OAB) is reduced by increased experience. Young experts (geriatric nurses) and controls performed a recognition experiment with young and old faces. Critically, while control participants demonstrated better memory for young faces, no OAB was observed in the experts. Event-related potentials revealed larger N170 and P2 amplitudes for young than old faces in both groups, suggesting no group differences during early perceptual processing. At test, N250 repetition effects were more anteriorily distributed for own- than other-age faces in control participants, whereas experts showed no corresponding effects. A larger late positive component (LPC) for old than young faces was observed in controls, but not in experts. Larger LPCs may reflect prolonged stimulus processing compromising memory retrieval. In sum, experience with other-age faces does not affect early perceptual processing, but modulates later stages related to memory retrieval.

  13. Docosahexaenoic acid has influence on action potentials and transient outward potassium currents of ventricular myocytes

    Directory of Open Access Journals (Sweden)

    Yang Zhen-Yu

    2010-04-01

    Full Text Available Abstract Background There are many reports about the anti-arrhythmic effects of ω-3 polyunsaturated fatty acids, however, the mechanisms are still not completely delineated. The purpose of this study was to investigate the characteristics of action potentials and transient outward potassium currents (Ito of Sprague-Dawley rat ventricular myocytes and the effects of docosahexaenoic acid (DHA on action potentials and Ito. Methods The calcium-tolerant rat ventricular myocytes were isolated by enzyme digestion. Action potentials and Ito of epicardial, mid-cardial and endocardial ventricular myocytes were recorded by whole-cell patch clamp technique. Results 1. Action potential durations (APDs were prolonged from epicardial to endocardial ventricular myocytes (P 2. Ito current densities were decreased from epicardial to endocardial ventricular myocytes, which were 59.50 ± 15.99 pA/pF, 29.15 ± 5.53 pA/pF, and 12.29 ± 3.62 pA/pF, respectively at +70 mV test potential (P 3. APDs were gradually prolonged with the increase of DHA concentrations from 1 μmol/L to 100 μmol/L, however, APDs changes were not significant as DHA concentrations were in the range of 0 μmol/L to 1 μmol/L. 4. Ito currents were gradually reduced with the increase of DHA concentrations from 1 μmol/L to 100 μmol/L, and its half-inhibited concentration was 5.3 μmol/L. The results showed that there were regional differences in the distribution of action potentials and Ito in rat epicardial, mid-cardial and endocardial ventricular myocytes. APDs were prolonged and Ito current densities were gradually reduced with the increase of DHA concentrations. Conclusion The anti-arrhythmia mechanisms of DHA are complex, however, the effects of DHA on action potentials and Ito may be one of the important causes.

  14. Multiple modes of action potential initiation and propagation in mitral cell primary dendrite

    DEFF Research Database (Denmark)

    Chen, Wei R; Shen, Gongyu Y; Shepherd, Gordon M

    2002-01-01

    The mitral cell primary dendrite plays an important role in transmitting distal olfactory nerve input from olfactory glomerulus to the soma-axon initial segment. To understand how dendritic active properties are involved in this transmission, we have combined dual soma and dendritic patch...... recordings with computational modeling to analyze action-potential initiation and propagation in the primary dendrite. In response to depolarizing current injection or distal olfactory nerve input, fast Na(+) action potentials were recorded along the entire length of the primary dendritic trunk. With weak......-initiation site reflected an independent thresholding mechanism in the distal dendrite. When strong olfactory nerve excitation was paired with strong inhibition to the mitral cell basal secondary dendrites, a small fast prepotential was recorded at the soma, which indicated that an action potential was initiated...

  15. Modeling and simulation of ion channels and action potentials in taste receptor cells

    Institute of Scientific and Technical Information of China (English)

    CHEN PeiHua; LIU Xiaodong; ZHANG Wei; ZHOU Jun; WANG Ping; YANG Wei; LUO JianHong

    2009-01-01

    Based on patch clamp data on the ionic currents of rat taste receptor cells,a mathematical model of mammalian taste receptor cells was constructed to simulate the action potentials of taste receptor cells and their corresponding ionic components,including voltage-gated Na~+ currents and outward delayed rectifier K~+ currents.Our simulations reproduced the action potentials of taste receptor cells in response to electrical stimuli or sour tastants.The kinetics of ion channels and their roles in action potentials of taste receptor cells were also analyzed.Our prototype model of single taste receptor cell and simulation results presented in this paper provide the basis for the further study of taste information processing in the gustatory system.

  16. Modeling and simulation of ion channels and action potentials in taste receptor cells

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Based on patch clamp data on the ionic currents of rat taste receptor cells, a mathematical model of mammalian taste receptor cells was constructed to simulate the action potentials of taste receptor cells and their corresponding ionic components, including voltage-gated Na+ currents and outward delayed rectifier K+ currents. Our simulations reproduced the action potentials of taste receptor cells in response to electrical stimuli or sour tastants. The kinetics of ion channels and their roles in action potentials of taste receptor cells were also analyzed. Our prototype model of single taste receptor cell and simulation results presented in this paper provide the basis for the further study of taste information processing in the gustatory system.

  17. Initiation and blocking of the action potential in the axon in a weak ultrasonic field

    CERN Document Server

    Shneider, M N

    2013-01-01

    It is shown that the longitudinal standing ultrasonic wave of low intensity leads to the lateral drift and to redistribution of the transmembrane ion channels in the initial segment of the myelinated axon of a neuron. The analysis is based on the Hodgkin - Huxley model of an axon. Redistribution of the density of transmembrane sodium channels, caused by ultrasound, may reduce the threshold of the action potential, up to its spontaneous initiation. At significant redistribution of sodium channels in membrane, the zones of rarefaction of the transmembrane channels density are formed blocking the propagation of the action potential. After switching the ultrasound off, the unperturbed uniform distribution of transmembrane channels in the axon recovers due to lateral diffusion. The blocking effect of the action potential can be used in anesthesia.

  18. 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.

  19. Phase lagging model of brain response to external stimuli - modeling of single action potential

    CERN Document Server

    Seetharaman, Karthik; Kulish, Vladimir V

    2012-01-01

    In this paper we detail a phase lagging model of brain response to external stimuli. The model is derived using the basic laws of physics like conservation of energy law. This model eliminates the paradox of instantaneous propagation of the action potential in the brain. The solution of this model is then presented. The model is further applied in the case of a single neuron and is verified by simulating a single action potential. The results of this modeling are useful not only for the fundamental understanding of single action potential generation, but also they can be applied in case of neuronal interactions where the results can be verified against the real EEG signal.

  20. An eikonal-curvature equation for action potential propagation in myocardium.

    Science.gov (United States)

    Keener, J P

    1991-01-01

    We derive an "eikonal-curvature" equation to describe the propagation of action potential wavefronts in myocardium. This equation is used to study the effects of fiber orientation on propagation in the myocardial wall. There are significant computational advantages to the use of an eikonal-curvature equation over a full ionic model of action potential spread. With this model, it is shown that the experimentally observed misalignment of spreading action potential "ellipses" from fiber orientation in level myocardial surfaces is adequately explained by the rotation of fiber orientation through the myocardial wall. Additionally, it is shown that apparently high propagation velocities on the epicardial and endocardial surfaces are the result of propagation into the midwall region and acceleration along midwall fibers before reemergence at an outer surface at a time preceding what could be accomplished with propagation along the surface alone.

  1. HEBAlt enhances the T-cell potential of fetal myeloid-biased precursors.

    Science.gov (United States)

    Braunstein, Marsela; Rajkumar, Paula; Claus, Carol L; Vaccarelli, Giovanna; Moore, Amanda J; Wang, Duncheng; Anderson, Michele K

    2010-12-01

    Hematopoiesis is controlled by the interplay between transcription factors and environmental signals. One of the primary determinants of the T-lineage choice is Delta-like (DL)-Notch signaling, which promotes T-cell development and inhibits B-cell development. We have found that the transcription factor HEBAlt is up-regulated in early hematopoietic precursors in response to DL-Notch signaling and that it can promote early T-cell development. Here, we identified a population of lineage-negative Sca-1⁻c-kit(+) (LK) cells in the mouse fetal liver that rapidly gave rise to myeloid cells and B cells but exhibited very little T-cell potential. However, forced expression of HEBAlt in these precursors restored their ability to develop into T cells. We also showed that Ikaros and Notch1 are up-regulated in response to HEBAlt over-expression and that activated Notch1 enhances the ability of LK cells to enter the T-cell lineage. Furthermore, the myeloid transcription factor C/EBPα is down-regulated in response to HEBAlt. We therefore propose that HEBAlt plays a role in the network that enforces the T-lineage fate and limits myeloid fate during hematopoiesis.

  2. Individuals' attentional bias toward an envied target's name: an event-related potential study.

    Science.gov (United States)

    Zhong, Jun; Liu, Yongfang; Zhang, Entao; Luo, Junlong; Chen, Jie

    2013-08-29

    Individuals may pay more attention to information about envied targets. Thus, we further investigate the neural correlates underlying the cognitive processing of envy-related stimuli. Participants read information about target persons characterized by two domains: levels of possession and self-relevance of comparison. Event-related potentials (ERPs) were then recorded for three target names (high-envy, moderate-envy, and low-envy) while participants performed a three-stimulus oddball task. The results showed that high- and moderate-envy target names elicited larger P300 amplitudes than did low-envy target names. Specifically, high-envy target names elicited larger P300 amplitudes than did low-envy target names at the left, central, and right sites; in contrast, moderate-envy target names elicited larger P300 amplitudes than did low-envy target names only at central sites. P300 amplitudes did not differ between high- and moderate-envy target names. Thus, we extend previous behavioral findings by showing that people preferentially attend toward envy-related stimuli, as reflected by enhanced P300 amplitudes.

  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. 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.

  5. Cardiac action potential repolarization re-visited: early repolarization shows all-or-none behaviour.

    Science.gov (United States)

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

    2017-08-17

    In healthy mammalian hearts the action potential (AP) waveform initiates and modulates each contraction, or heartbeat. As a result, action potential height and duration are key physiological variables. In addition, rate-dependent changes in ventricular action potential 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 also draws attention to the early repolarization phase of the action potential (and the J wave of the ECG) as a biomarker for arrhythmogenesis. Here we provide 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 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 as well as alter APD stability, and modulate responsiveness to pharmacological agents (such as Class III anti-arrhythmic drugs). This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  6. Effects of some heavy metals on the action potentials of an identified Helix pomatia photosensitive neuron.

    Science.gov (United States)

    Kartelija, Gordana; Radenović, Lidija; Todorović, Natasa; Nedeljković, Miodrag

    2005-06-01

    In the photosensitive MB neuron in the left parietal ganglion of Helix pomatia, the onset of light prolongs significantly (by about 40%) the duration of the action potential. The broadening of the action potential after the onset of light was found to be due to its calcium component and could not be induced after blocking Ca(2+) channels by Cd(2+) and Pb(2+) and in absence of Ca(2+) in medium. The blocking effect of both compounds was reversible. It was found that CdCl(2) exhibited a more intense blocking effect than PbCl(2).

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

    DEFF Research Database (Denmark)

    Jensen, A. S.; Pennisi, C. P.; Sevcencu, C.;

    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...

  8. Attenuation by phentolamine of hypoxia and levcromakalim-induced abbreviation of the cardiac action potential.

    OpenAIRE

    Tweedie, D.; Boachie-Anash, G.; Henderson, C. G.; Kane, K. A.

    1993-01-01

    1. The effects of phentolamine (5-30 microM) and glibenclamide (10 microM) on action potential characteristics were examined in guinea-pig papillary muscle exposed to either hypoxia or levcromakalim (20 microM). 2. The hypoxia-induced abbreviation of action potential duration (APD) and effective refractory period (ERP) were attenuated but not abolished by glibenclamide (10 microM). Hypoxia reduced APD by 24 +/- 2 vs 65 +/- 4% in glibenclamide- and vehicle-treated tissue, respectively. 3. Phen...

  9. 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.

  10. 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. PMID:27525414

  11. 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.

  12. Ca2+ involvement in the action potential generation of myenteric neurones in the rat oesophagus.

    Science.gov (United States)

    De Laet, A; Cornelissen, W; Adriaensen, D; Van Bogaert, P-P; Scheuermann, D W; Timmermans, J-P

    2002-04-01

    Intracellular recordings were used to study the physiological behaviour of rat oesophageal myenteric neurones, which are embedded in striated muscle. Injection of depolarizing pulses evoked action potentials with a clear 'shoulder' in all neurones. This shoulder disappeared under low Ca2+/high Mg2+ conditions. Tetrodotoxin (TTX; 1 micromol L-1) did not impede spike firing, whereas under combined TTX and low Ca2+/high Mg2+ conditions the action potentials were completely abolished, indicating that TTX- resistant action potentials are mediated by a Ca2+ current. Further experiments with omega-conotoxin GVIA (100 nmol L-1) revealed that these Ca2+ currents enter the cell via N-type voltage-activated Ca2+ channels (see also accompanying paper). Tetraethylammonium (10 mmol L-1) caused broadening of the action potentials, which probably resulted from prolonged Ca2+ influx due to blockade of the delayed rectifier K+ channel. Although Ca2+ appears to be involved in the spike generation of all rat oesophageal myenteric neurones, only a minority (14%) shows a slow afterhyperpolarization. Thus, no strict correlation exists between the presence of a shoulder and a slow afterhyperpolarization. Furthermore, morphological identification of 25 of the impaled neurones revealed that there was no strict correlation between morphology and electrophysiological behaviour. Consequently, rat oesophageal myenteric neurones appear to differ in several aspects from myenteric neurones in smooth muscle regions of the gastrointestinal tract.

  13. 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

    Glucagon-like peptide-2 (GLP-2) is a nutrient-regulated intestinotrophic hormone derived from proglucagon in the distal intestine. Enteral nutrients (EN) potentiate the action of GLP-2 to reverse parenteral nutrition (PN)-induced mucosal hypoplasia. The objective was to determine what enteral...

  14. Youth Participatory Action Research and Educational Transformation: The Potential of Intertextuality as a Methodological Tool

    Science.gov (United States)

    Bertrand, Melanie

    2016-01-01

    In this article, Melanie Bertrand explores the potential of using the concept of intertextuality--which captures the way snippets of written or spoken text from one source become incorporated into other sources--in the study and practice of youth participatory action research (YPAR). Though this collective and youth-centered form of research…

  15. 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.

  16. 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.

    2017-01-01

    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…

  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. Zinc-dependent action potentials in giant neurons of the snail, Euhadra quaestia.

    Science.gov (United States)

    Kawa, K

    1979-09-14

    In giant neurons of subesophageal ganglion of the Japanese land snail, Euhadra quaestia Deshayes, permeation of Zn ions through Ca channels were investigated with a conventional current clamp method. All-or-none action potentials of long duration (90 to 120 sec) were evoked in 24 mM Zn containing salines. The overshoots were about +10 mV and the maximum rate of rises (MRRs) was about 2.9 V/sec. The amplitudes and the MRRs of the action potentials depended on external Zn ion concentrations. The action potentials were suppressed by specific Ca-channel inhibitors such as Co2+, La3+ and Verapamil, but they were resistant to Na-channel inhibitor, tetrodotoxin, even at 30 microM. It is concluded that these action potentials are generated by Zn ions permeating Ca channels in snail neuronal membrane. On the basis of Hagiwara and Takahashi's (S. Hagiwara & K. Takahashi, 1967, J. Gen. Physiol. 50:583) model of Ca channels, it is inferred that Zn ions are 5 to 10 times stronger in affinity to Ca channels than Ca ions, but 10 to 20 times less permeable.

  19. 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...... of EADs. Our results suggest a potential benefit of K(+) current activators under conditions of reduced repolarization reserve including heart failure....

  20. Origin of ulnar compound muscle action potential investigated in patients with ulnar neuropathy at the wrist.

    Science.gov (United States)

    Higashihara, Mana; Sonoo, Masahiro; Imafuku, Ichiro; Ugawa, Yoshikazu; Tsuji, Shoji

    2010-05-01

    The compound muscle action potential from the abductor digiti minimi muscle is bi-lobed, and its second peak is formed by far-field potentials (FFPs). We investigated their origin in two patients with ulnar neuropathy at the wrist that spared the hypothenar muscles. FFPs were lost or distorted, which indicated that the deep motor branch-innervated muscles, such as the interossei, mainly contributed to the FFPs, especially to their initial N1 and steep following P1 components.

  1. Effects of benactyzine on action potentials and contractile force of guinea pig papillary muscles

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Aim:To explore the effects of benactyzine (BEN) on the action potential and contractile force in guinea pig papillary muscles.Methods:Conventional microelectrode technique was used to record the fast action potentials (FAP) and slow action potentials (SAP) of guinea pig papillary muscles.Results:Benactyzine 5,10,50 μmol·L-1 suppressed the maximal upstroke velocity (vmax) of FAP and contractile force (Fc) concentration-dependently while prolonged the action potential duration at 50%,90% repolarization (APD50,APD90) and effective refractory period (ERP) of FAP.The suppression on the vmax was frequency-dependent.Benactyzine 5,10,50μmol·L-1 lengthened the APD50,APD90 of SAP induced by isoprenaline or histamine when perfused with KCl 22 mmol·L-1 Tyrode's solution.The vmax of the SAP was not decreased by benactyzine 5,10 μmol·L-1 but by 50 μmol·L-1.The effects on the SAP were antagonized by elevation of the extracellular calcium from 2.0 to 5.6 mmol·L-1.The effects of benactyzine on SAP elicited by tetrodotoxin resembled that by isoprenaline or histamine except the more pronounced suppression on vmax and action potential amplitude (APA).The persistent rapid spontaneous activity and triggered tachyarrhythmia induced by ouabain were also abolished immediately by benactyzine 5 μmol·L-1.Conclusion:Benactyzine can inhibit Na+,K+,Ca2+ transmembrane movement and intracellular Ca2+ mobilization in the myocardium,and this may be the electrophysiological basis of its effects against experimental arrhythmias.

  2. A critical appraisal of epidemiological studies comes from basic knowledge: A reader's guide to assess potential for biases

    NARCIS (Netherlands)

    S. Boccia (Stefania); G.L. Torre; R. Persiani (Roberto); D. D'Ugo (Domenico); P. Tikka-Kleemola (Päivi); G. Ricciardi (Gualtiero)

    2007-01-01

    textabstractScientific literature may be biased because of the internal validity of studies being compromised by different forms of measurement error, and/or because of the selective reporting of positive and 'statistically significant' results. While the first source of bias might be prevented, and

  3. An Examination of Potential Racial and Gender Bias in the Principal Version of the Interactive Computer Interview System

    Science.gov (United States)

    DiPonio, Joseph M.

    2010-01-01

    The primary object of this study was to determine whether racial and/or gender bias were evidenced in the use of the ICIS-Principal. Specifically, will the use of the ICIS-Principal result in biased scores at a statistically significant level when rating current practicing administrators of varying gender and race. The study involved simulated…

  4. Testing for potential contextual bias effects during the verification stage of the ACE-V methodology when conducting fingerprint comparisons.

    Science.gov (United States)

    Langenburg, Glenn; Champod, Christophe; Wertheim, Pat

    2009-05-01

    This study was conducted to assess if fingerprint specialists could be influenced by extraneous contextual information during a verification process. Participants were separated into three groups: a control group (no contextual information was given), a low bias group (minimal contextual information was given in the form of a report prompting conclusions), and a high bias group (an internationally recognized fingerprint expert provided conclusions and case information to deceive this group into believing that it was his case and conclusions). A similar experiment was later conducted with laypersons. The results showed that fingerprint experts were influenced by contextual information during fingerprint comparisons, but not towards making errors. Instead, fingerprint experts under the biasing conditions provided significantly fewer definitive and erroneous conclusions than the control group. In contrast, the novice participants were more influenced by the bias conditions and did tend to make incorrect judgments, especially when prompted towards an incorrect response by the bias prompt.

  5. Biased predecision processing.

    Science.gov (United States)

    Brownstein, Aaron L

    2003-07-01

    Decision makers conduct biased predecision processing when they restructure their mental representation of the decision environment to favor one alternative before making their choice. The question of whether biased predecision processing occurs has been controversial since L. Festinger (1957) maintained that it does not occur. The author reviews relevant research in sections on theories of cognitive dissonance, decision conflict, choice certainty, action control, action phases, dominance structuring, differentiation and consolidation, constructive processing, motivated reasoning, and groupthink. Some studies did not find evidence of biased predecision processing, but many did. In the Discussion section, the moderators are summarized and used to assess the theories.

  6. 'Catching the waves' - slow cortical potentials as moderator of voluntary action.

    Science.gov (United States)

    Schmidt, Stefan; Jo, Han-Gue; Wittmann, Marc; Hinterberger, Thilo

    2016-09-01

    The readiness potential is an ongoing negativity in the EEG preceding a self-initiated movement by approximately 1.5s. So far it has predominantly been interpreted as a preparatory signal with a causal link to the upcoming movement. Here a different hypothesis is suggested which we call the selective slow cortical potential sampling hypothesis. In this review of recent research results we argue that the initiation of a voluntary action is more likely during negative fluctuations of the slow cortical potential and that the sampling and averaging of many trials leads to the observed negativity. That is, empirical evidence indicates that the early readiness potential is not a neural correlate of preconscious motor preparation and thus a determinant of action. Our hypothesis thereafter challenges the classic interpretation of the Libet experiment which is often taken as proof that there is no free will. We furthermore suggest that slow cortical potentials are related to an urge to act but are not a neural indicator of the decision process of action initiation.

  7. Phorbol esters broaden the action potential in CA1 hippocampal pyramidal cells.

    Science.gov (United States)

    Storm, J F

    1987-03-20

    Intracellular recordings were made from CA1 pyramidal cells in rat hippocampal slices. Single action potentials were elicited by injection of brief current pulses. Bath application of phorbol esters (4 beta-phorbol-12,13-diacetate, 0.3-5 microM; or 4 beta-phorbol-12,13-dibutyrate, 5-10 microM) broadened the action potential in each of the cells tested (n = 9). The broadening reflected slowing of the repolarization, whereas the upstroke of the spike was unchanged. This effect may enhance transmitter release from synaptic terminals, and contribute to enhancement of synaptic transmission through activation of protein kinase C, a mechanism which has been associated with long term potentiation.

  8. In Silico Evaluation of the Potential Impact of Bioanalytical Bias Difference between Two Therapeutic Protein Formulations for Pharmacokinetic Assessment in a Biocomparability Study.

    Science.gov (United States)

    Thway, Theingi M; Macaraeg, Chris; Eschenberg, Michael; Ma, Mark

    2015-05-01

    Formulation changes at later stages of biotherapeutics development require biocomparability (BC) assessment. Using simulation, this study aims to determine the potential effect of bias difference observed between the two formulations after spiking into serum in passing or failing of a critical BC study. An ELISA method with 20% total error was used to assess any bias differences between a reference (RF) and test formulations (TF) in serum. During bioanalytical comparison of these formulations, a 9% difference in bias was observed between the two formulations in sera. To determine acceptable level of bias difference between the RF and TF bioanalytically, two in silico simulations were performed. The in silico analysis showed that the likelihood of the study meeting the BC criteria was >90% when the bias difference between RF and TF in serum was 9% and the number of subjects was ≥20 per treatment arm. An additional simulation showed that when the bias difference was increased to 13% and the number of subjects was silico analysis allowed the bioanalytical laboratory to proceed with sample analysis using a single calibrator and quality controls made from the reference formulation. This modeling approach can be applied to other BC studies with similar situations.

  9. A potential gender bias in assessing quality of life – a standard gamble experiment among university students

    Directory of Open Access Journals (Sweden)

    Al Obaidi L

    2015-04-01

    Full Text Available Leath Al Obaidi,1 Jörg Mahlich2,3 1University of Nottingham, School of Economics, Nottingham, UK; 2Health Economics, Janssen KK, Tokyo, Japan; 3Düsseldorf Institute for Competition Economics (DICE, University of Düsseldorf, Düsseldorf, Germany Background: There are several methodologies that can be used for evaluating patients' perception of their quality of life. Most commonly, utilities are directly elicited by means of either the time-trade-off or the standard-gamble method. In both methods, risk attitudes determine the quality of life values. Methods: Quality of life values among 31 Austrian undergraduate students were elicited by means of the standard gamble approach. The impact of several variables such as gender, side job, length of study, and living arrangements on the quality of life were identified using different types of regression techniques (ordinary least squares, generalized linear model, Betafit. Results: Significant evidence was found that females are associated with a higher quality of life in all specifications of our estimations. Discussion: The observed gender differences in quality of life can be attributed to a higher degree of risk aversion of women. A higher risk aversion leads to a higher valuation of given health states and a potential gender bias in health economic evaluations. This result could have implications for health policy planners when it comes to budget allocation decisions. Keywords: quality of life, gender, risk aversion, standard gamble, students 

  10. 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

  11. A critical appraisal of epidemiological studies comes from basic knowledge: a reader's guide to assess potential for biases

    Directory of Open Access Journals (Sweden)

    van Duijn Cornelia M

    2007-03-01

    Full Text Available Abstract Scientific literature may be biased because of the internal validity of studies being compromised by different forms of measurement error, and/or because of the selective reporting of positive and 'statistically significant' results. While the first source of bias might be prevented, and in some cases corrected to a degree, the second represents a pervasive problem afflicting the medical literature; a situation that can only be 'corrected' by a change in the mindset of authors, reviewers, and editors. This review focuses on the concepts of confounding, selection bias and information bias, utilising explanatory examples and simple rules to recognise and, when possible, to correct for them. Confounding is a mixing of effects resulting from an imbalance of some of the causes of disease across the compared groups. It can be prevented by randomization and restriction, and controlled by stratification, standardization or by using multivariable techniques. Selection bias stems from an absence of comparability among the groups being studied, while information bias arises from distorted information collection techniques. Publication bias of medical research results can invalidate evidence-based medicine, when a researcher attempting to collect all the published studies on a specific topic actually gathers only a proportion of them, usually the ones reporting 'positive' results. The selective publication of 'statistically significant' results represents a problem that researchers and readers have to be aware of in order to face the entire body of published medical evidence with a degree of scepticism.

  12. A critical appraisal of epidemiological studies comes from basic knowledge: a reader's guide to assess potential for biases

    Science.gov (United States)

    Boccia, Stefania; La Torre, Giuseppe; Persiani, Roberto; D'Ugo, Domenico; van Duijn, Cornelia M; Ricciardi, Gualtiero

    2007-01-01

    Scientific literature may be biased because of the internal validity of studies being compromised by different forms of measurement error, and/or because of the selective reporting of positive and 'statistically significant' results. While the first source of bias might be prevented, and in some cases corrected to a degree, the second represents a pervasive problem afflicting the medical literature; a situation that can only be 'corrected' by a change in the mindset of authors, reviewers, and editors. This review focuses on the concepts of confounding, selection bias and information bias, utilising explanatory examples and simple rules to recognise and, when possible, to correct for them. Confounding is a mixing of effects resulting from an imbalance of some of the causes of disease across the compared groups. It can be prevented by randomization and restriction, and controlled by stratification, standardization or by using multivariable techniques. Selection bias stems from an absence of comparability among the groups being studied, while information bias arises from distorted information collection techniques. Publication bias of medical research results can invalidate evidence-based medicine, when a researcher attempting to collect all the published studies on a specific topic actually gathers only a proportion of them, usually the ones reporting 'positive' results. The selective publication of 'statistically significant' results represents a problem that researchers and readers have to be aware of in order to face the entire body of published medical evidence with a degree of scepticism. PMID:17359550

  13. Variations in onset of action potential broadening: effects on calcium current studied in chick ciliary ganglion neurones.

    Science.gov (United States)

    Pattillo, J M; Artim, D E; Simples, J E; Meriney, S D

    1999-02-01

    1. The voltage dependence and kinetic properties of stage 40 ciliary ganglion calcium currents were determined using short (10 ms) voltage steps. These properties aided the interpretation of the action potential-evoked calcium current described below, and the comparison of our data with those observed in other preparations. 2. Three different natural action potential waveforms were modelled by a series of ramps to generate voltage clamp commands. Calcium currents evoked by these model action potentials were compared before and after alterations in the repolarization phase of each action potential. 3. Abrupt step repolarizations from various time points were used to estimate the time course of calcium current activation during each action potential. Calcium current evoked by fast action potentials (duration at half-amplitude, 0.5 or 1.0 ms) did not reach maximal activation until the action potential had repolarized by 40-50 %. In contrast, calcium current evoked by a slow action potential (duration at half-amplitude, 2.2 ms) was maximally activated near the peak of the action potential. 4. Slowing the rate of repolarization of the action potential (broadening) from different times was used to examine effects on peak and total calcium influx. With all three waveforms tested, broadening consistently increased total calcium influx (integral). However, peak calcium current was either increased or decreased depending on the duration of the control action potential tested and the specific timing of the initiation of broadening the repolarization phase. 5. The opposite effects on peak calcium current observed with action potential broadening beginning at different time points in repolarization may provide a mechanism for the variable effects of potassium channel blockers on transmitter release magnitude.

  14. Sex-biased miRNAs in gonad and their potential roles for testis development in yellow catfish.

    Science.gov (United States)

    Jing, Jing; Wu, Junjie; Liu, Wei; Xiong, Shuting; Ma, Wenge; Zhang, Jin; Wang, Weimin; Gui, Jian-Fang; Mei, Jie

    2014-01-01

    Recently, YY super-male yellow catfish had been created by hormonal-induced sex reversal and sex-linked markers, which provides a promising research model for fish sex differentiation and gonad development, especially for testis development. MicroRNAs (miRNAs) have been revealed to play crucial roles in the gene regulation and gonad development in vertebrates. In this study, three small RNA libraries constructed from gonad tissues of XX female, XY male and YY super-male yellow catfish were sequenced. The sequencing data generated a total of 384 conserved miRNAs and 113 potential novel miRNAs, among which 23, 30 and 14 miRNAs were specifically detected in XX ovary, XY testis, and YY testis, respectively. We observed relative lower expression of several miR-200 family members, including miR-141 and miR-429 in YY testis compared with XY testis. Histological analysis indicated a higher degree of testis maturity in YY super-males compared with XY males, as shown by larger spermatogenic cyst, more spermatids and fewer spermatocytes in the spermatogenic cyst. Moreover, five miR-200 family members were significantly up-regulated in testis when treated by 17α-ethinylestradiol (EE2), high dose of which will impair testis development and cell proliferation. The down-regulation of miR-141 and 429 coincides with the progression of testis development in both yellow catfish and human. At last, the expression pattern of nine arbitrarily selected miRNAs detected by quantitative RT-PCR was consistent with the Solexa sequencing results. Our study provides a comprehensive miRNA transcriptome analysis for gonad of yellow catfish with different sex genotypes, and identifies a number of sex-biased miRNAs, some of that are potentially involved in testis development and spermatogenesis.

  15. The mode of action of quinidine on isolated rabbit atria interpreted from intracellular potential records.

    Science.gov (United States)

    VAUGHAN WILLIAMS, E M

    1958-09-01

    An attempt has been made to show why quinidine, which has long been known not to lengthen the duration of the cardiac action potential, measured with external electrodes, and also not to lengthen, and sometimes to shorten, the absolute refractory period, nevertheless reduces the maximum frequency at which atria can respond to a stimulus. Simultaneous measurements have been made in electrically driven isolated rabbit atria of contractions, conduction velocity and intracellular potentials before and during exposure to a wide range of concentrations of quinidine sulphate. The resting potential remained undiminished, in contrast to the effect of quinidine on Purkinje fibres. In the therapeutic range of doses, up to 10 mg./l., the half-time for repolarization was either shortened or unchanged, thus providing an explanation for the failure of quinidine to prolong the absolute refractory period. In contrast, even at low concentrations of quinidine, conduction velocity and the rate of rise of the action potential were greatly slowed, and the height of the overshoot was reduced. The terminal phase of the action potential was prolonged. It is known that the rate of rise of the action potential is a function of the level of repolarization at which an impulse takes off (the more negative the take-off point, the faster the rate of rise). Normally, a stimulus introduced when repolarization has proceeded to 2/3 of the resting potential evokes a response with a rate of rise fast enough for propagation, so that the duration of the terminal 1/3 of the phase of repolarization has no influence upon the length of the effective refractory period. In the presence of quinidine, however, the rate of rise itself was directly reduced, thus repolarization had to proceed further before the critical take-off point was reached at which the rate of rise was fast enough for propagation, and the duration of the terminal phase of repolarization thus became significant. It has been concluded that

  16. An experimental study on a function of the cupula. Effect of cupula removal on the ampullary nerve action potential.

    Science.gov (United States)

    Suzuki, M; Harada, Y; Sugata, Y

    1984-01-01

    We used a posterior semicircular canal that had been isolated from a frog. From the utricular side the ampulla was cut open at a position one third of the way along the long axis. The cupula was removed through this opening using a glass micropipette. The action potential from the posterior ampullary nerve was recorded before and after removal of the cupula. After removal, the action potential disappeared almost completely. When the cupula was put back on the crista, the action potential was restored. When the cupula was put back upside down, the action potential recovered, but to a lesser extent.

  17. The DBI Action, Higher-derivative Supergravity, and Flattening Inflaton Potentials

    CERN Document Server

    Bielleman, Sjoerd; Pedro, Francisco G; Valenzuela, Irene; Wieck, Clemens

    2016-01-01

    In string theory compactifications it is common to find an effective Lagrangian for the scalar fields with a non-canonical kinetic term. We study the effective action of the scalar position moduli of Type II D$p$-branes. In many instances the kinetic terms are in fact modified by a term proportional to the scalar potential itself. This can be linked to the appearance of higher-dimensional supersymmetric operators correcting the K\\"ahler potential. We identify the supersymmetric dimension-eight operators describing the $\\alpha'$ corrections captured by the D-brane Dirac-Born-Infeld action. Our analysis then allows an embedding of the D-brane moduli effective action into an $\\mathcal N = 1$ supergravity formulation. The effects of the potential-dependent kinetic terms may be very important if one of the scalars is the inflaton, since they lead to a flattening of the scalar potential. We analyze this flattening effect in detail and compute its impact on the CMB observables for single-field inflation with monomia...

  18. Examining the Potential for Gender Bias in the Prediction of Symptom Validity Test Failure by MMPI-2 Symptom Validity Scale Scores

    Science.gov (United States)

    Lee, Tayla T. C.; Graham, John R.; Sellbom, Martin; Gervais, Roger O.

    2012-01-01

    Using a sample of individuals undergoing medico-legal evaluations (690 men, 519 women), the present study extended past research on potential gender biases for scores of the Symptom Validity (FBS) scale of the Minnesota Multiphasic Personality Inventory-2 by examining score- and item-level differences between men and women and determining the…

  19. Examining the Potential for Gender Bias in the Prediction of Symptom Validity Test Failure by MMPI-2 Symptom Validity Scale Scores

    Science.gov (United States)

    Lee, Tayla T. C.; Graham, John R.; Sellbom, Martin; Gervais, Roger O.

    2012-01-01

    Using a sample of individuals undergoing medico-legal evaluations (690 men, 519 women), the present study extended past research on potential gender biases for scores of the Symptom Validity (FBS) scale of the Minnesota Multiphasic Personality Inventory-2 by examining score- and item-level differences between men and women and determining the…

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

    Science.gov (United States)

    French, A S

    1984-08-01

    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 direct electrical stimulation of the sensory cell axon and found a dynamic response that is identical to the response given by mechanical stimulation. This indicates that the fractional differentiation is a property of the encoder rather than the transducer.

  1. 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

  2. Regulation of cough and action potentials by voltage-gated Na channels.

    Science.gov (United States)

    Carr, Michael J

    2013-10-01

    The classical role ascribed to voltage-gated Na channels is the conduction of action potentials. Some excitable tissues such as cardiac muscle and skeletal muscle predominantly express a single voltage-gated Na channels isoform. Of the nine voltage-gated Na channels, seven are expressed in neurons, of these Nav 1.7, 1.8 and 1.9 are expressed in sensory neurons including vagal sensory neurons that innervate the airways and initiate cough. Nav 1.7 and Nav 1.9 are of particular interest as they represent two extremes in the functional diversity of voltage-gated Na channels. Voltage-gated Na channel isoforms expressed in airway sensory neurons produce multiple distinct Na currents that underlie distinct aspects of sensory neuron function. The interaction between voltage-gated Na currents underlies the characteristic ability of airway sensory nerves to encode encounters with irritant stimuli into action potential discharge and evoke the cough reflex.

  3. Activity dependence of action potential duration in rat supraoptic neurosecretory neurones recorded in vitro.

    Science.gov (United States)

    Bourque, C W; Renaud, L P

    1985-06-01

    Action potential durations, measured at one-third peak amplitude, were examined during intracellular recordings in 134 supraoptic nucleus neurones maintained in vitro in perfused hypothalamic explants. Spike durations ranged between 1.2 and 3.9 ms and were dependent on firing frequency. Shortest measurements (1.74 +/- 0.03 ms; mean +/- S.E. of mean) were obtained during relative quiescence, i.e. less than or equal to 0.5 Hz. A gradual increase in firing frequency through continuous injection of depolarizing current prolonged spike duration, with maximum levels (2.68 +/- 0.05 ms) achieved at 20 Hz. When interspike interval variability was eliminated and firing was more precisely regulated by brief 15-20 ms intracellular current pulses given at pre-determined frequencies, a proportional relationship between increasing spike duration and firing frequency was retained but the change in spike duration at frequencies between 2 and 10 Hz was less pronounced. Once action potentials had achieved the long duration configuration, their return to the shorter duration took place gradually during any succeeding silent interval with a time constant of 4.9 s. Action potential broadening occurred progressively and was most pronounced at the onset of spontaneous or current-induced bursts. In thirty-six phasically active neurones, spike broadening at the onset of a burst was concurrent with the presence of 5-10 consecutive short (less than or equal to 100 ms) interspike intervals; thereafter, despite a greater than 50% reduction in firing frequency, action potential durations remained prolonged throughout the burst. In all of nineteen cells tested, frequency-dependent changes in spike duration were reversibly decreased or blocked by Cd2+, Co2+ and Mn2+, or when CaCl2 was exchanged for equimolar amounts of EGTA in the perfusion medium. These observations indicate that a Ca2+ conductance contributes to frequency- and firing-pattern-dependent changes in spike duration in rat supraoptic

  4. SHAPING OF ACTION POTENTIALS BY TYPE I AND TYPE II BK CHANNELS

    OpenAIRE

    Jaffe, David B.; Wang, Bin; Brenner, Robert

    2011-01-01

    The BK channel is a Ca2+ and voltage-gated conductance responsible for shaping action potential waveforms in many types of neurons. Type II BK channels are differentiated from type I channels by their pharmacology and slow gating kinetics. The β4 accessory subunit confers type II properties on BK α subunits. Empirically derived properties of BK channels, with and without the β4 accessory subunit, were obtained using a heterologous expression system under physiological ionic conditions. These ...

  5. FMRP Regulates Neurotransmitter Release and Synaptic Information Transmission by Modulating Action Potential Duration via BK channels

    OpenAIRE

    Deng, Pan-Yue; Rotman, Ziv; Blundon, Jay A.; Cho, Yongcheol; Cui, Jianmin; Cavalli, Valeria; Zakharenko, Stanislav S; Klyachko, Vitaly A.

    2013-01-01

    Loss of FMRP causes Fragile X syndrome (FXS), but the physiological functions of FMRP remain highly debatable. Here we show that FMRP regulates neurotransmitter release in CA3 pyramidal neurons by modulating action potential (AP) duration. Loss of FMRP leads to excessive AP broadening during repetitive activity, enhanced presynaptic calcium influx and elevated neurotransmitter release. The AP broadening defects caused by FMRP loss have a cell-autonomous presynaptic origin and can be acutely r...

  6. A Study of Surface Motor Unit Action Potentials in First Dorsal Interosseus (FDI) Muscle

    Science.gov (United States)

    2007-11-02

    Lefever and Carlo J. Deluca, "A Procedure for Decomposing the Myoelectric Signal Into It’s Constituent Action Potentials---Part 1, Technique, Theory, and...of surface MUAP’s using wavelet matching technique. II. SURFACE MUAP’S AND WAVELETS EMG signals are composed of different MUAP’s. Each...displays an impulse property, which means that it changes in a rapid fashion. Due to this property, the EMG signal is well suited to wavelet analysis

  7. Action potential characteristics of demyelinated rat sciatic nerve following application of 4-aminopyridine.

    Science.gov (United States)

    Targ, E F; Kocsis, J D

    1986-01-15

    The sciatic nerves of rats were demyelinated by microinjection of lysophosphatidylcholine. A variety of abnormalities such as conduction slowing and block were present. Application of the potassium channel blocker 4-aminopyridine (4-AP) to the lesion site, led to an increase in area of the compound action potential recorded across the site of demyelination. Single axon recordings revealed three types of changes that may account for the 4-AP-induced increase in the compound response. One group showed broadening of the action potential. Other axons showed hyperexcitability following 4-AP, as manifest by spontaneous firing and multiple spike discharge following a single stimulus. In some of the axons studied, 4-AP led to overcoming of conduction block. Although many axons showed increased excitability properties in the presence of 4-AP, the frequency-following ability of the axons was reduced, and the absolute refractory period of the axons was increased. These results indicate that pharmacological blockade of potassium channels with 4-AP not only leads to action potential broadening in demyelinated axons, but to a variety of excitability changes. These heterogeneous effects of 4-AP should be considered in the rationale for its clinical use.

  8. Noisy unmaskers of multistability of periodic rhythms in a model of the ventricular cardiac action potential

    Science.gov (United States)

    Surovyatkina, Elena; Egorchenkov, Roman; Ivanov, Guennady

    2007-06-01

    The coexistence of different dynamical regimes of cardiac cell-model at a fixed set of stimulation parameters, i.e. multistability, revealed by noise is presented in this paper. Numerical simulations are performed using Luo-Rudy (LR1) action potential model. Numerical experiments with LR1 model conducted via noisy periodical stimulation showed the coexistence of several periodic rhythms. Weak noise in period of stimulation causes a hopping process between all the (meta-) stable rhythms of cell-model. This process is reflected in several parallel branches of the bifurcation diagram: noise unveils new, invisible before, stable rhythms which could appear in this model at different initial conditions. The phenomenon of multistability is directly evidenced by other numerical experiments: we have established the multistability property of a cell consisting in the fact that different initial conditions of stimulation (different extrasystole application times) lead to different stable periodic rhythms. We have obtained the shaping of attraction basins on the action potential curves. Such basins of attraction contain a set of initial conditions which determinate a stable periodic rhythm. We have found a close association between the attraction basins of the complex rhythms on the curves of action potential and the cardiac vulnerable windows on ECG record, during which extra stimuli can induce life threatening arrhythmias. Obtained results allow us to make a conclusion that multistability is very important for the electrical conduction system of the heart from the cell level to the integrated function of the heart.

  9. Mephenesin, methocarbamol, chlordiazepoxide and diazepam: actions on spinal reflexes and ventral root potentials.

    Science.gov (United States)

    Crankshaw, D P; Raper, C

    1970-01-01

    1. Dose levels of mephenesin, methocarbamol, chlordiazepoxide and diazepam which abolished polysynaptic reflex contractions had no effect on monosynaptic knee-jerk reflexes in chloralose anaesthetized cats.2. Ventral root potentials were recorded following stimulation of the corresponding dorsal root (L7 or S1), and the areas of the mono- and polysynaptic components were measured by planimetry.3. Dose levels of the drugs which abolished polysynaptic reflex contractions reduced the areas of the polysynaptic component of the ventral root potentials by about 50%. Mephenesin and methocarbamol reduced the area of the monosynaptic component to a similar extent. Chlordiazepoxide was less potent in this respect while diazepam was without effect at this dose level.4. Linear regression lines were calculated for the reduction in the mono- and polysynaptic components of ventral root potentials with increasing doses of each of the four drugs. With methocarbamol and mephenesin the lines were parallel and coincident. With chlordiazepoxide and diazepam they were parallel but not coincident. Large doses of diazepam were required to reduce the area of the monosynaptic component, this drug being the only one of the four tested to have a differential action on the two components which was statistically significant.5. The results are discussed in terms of depressant actions of the drugs on alpha-motorneurones, effects of the drugs at higher centres concerned with motor function, and the lack of evidence that spinal interneurones represent a specific site of action for centrally acting skeletal muscle relaxants.

  10. [Muscle action potential and masticatory rhythm of anterior temporal and masseter muscles in children and adults].

    Science.gov (United States)

    Alvarado Larrinaga, G; Takarada, T; Nishida, F; Nishino, M

    1989-01-01

    For the investigation of the functional change of the masticatory muscles along with growth and development, electromyographic evaluation was carried out. The subjects were 6 children (5 males and 1 female) with full deciduous dentition (Hellman's dental age IIA) aged 4.5 +/- 0.2 years and 6 adults (4 males and 2 females) with full permanent dentition aged 27.7 +/- 3.8 years. EMG signals were recorded bilaterally by means of bipolar silver surface electrodes from the anterior temporal and masseter muscles when the subjects were chewing chewing gum or performing maximum clenches in intercuspal position. The cumulative power values from 62.5 to 1000 Hz in the EMG power spectrum during chewing or clenching were calculated as the muscle action potential. The ratio of the action potential of each muscle to the total action potential of four muscles were analyzed. Masticatory rhythm during chewing was analyzed by means of the time parameter (duration, interval and cycle) and their coefficients of variation. The results were as follows: 1. In children the temporal muscles predominated in chewing and clenching, whereas in adults there were three types with Temporal muscles predominating, Masseter muscles predominating and both muscles sharing equally. 2. No statistically significant differences between children and adults were observed in the duration, interval and cycle. 3. In adults the coefficients of variation of the duration, interval and cycle were smaller and the masticatory rhythm was more stable than in children.

  11. Media Bias

    OpenAIRE

    Sendhil Mullainathan; Andrei Shleifer

    2002-01-01

    There are two different types of media bias. One bias, which we refer to as ideology, reflects a news outlet's desire to affect reader opinions in a particular direction. The second bias, which we refer to as spin, reflects the outlet's attempt to simply create a memorable story. We examine competition among media outlets in the presence of these biases. Whereas competition can eliminate the effect of ideological bias, it actually exaggerates the incentive to spin stories.

  12. Looking at the sunny side of life: age-related change in an event-related potential measure of the negativity bias.

    Science.gov (United States)

    Kisley, Michael A; Wood, Stacey; Burrows, Christina L

    2007-09-01

    Studies of the negativity bias have demonstrated that negative information has a stronger influence than positive information in a wide range of cognitive domains. At odds with this literature is extensive work now documenting emotional and motivational shifts that result in a positivity effect in older adults. It remains unclear, however, whether this age-related positivity effect results from increases in processing of positive information or from decreases in processing of negative information. Also unknown is the specific time course of development from a negative bias to an apparently positive one. The present study was designed to investigate the negativity bias across the life span using an event-related potential measure of responding to emotionally valenced images. The results suggest that neural reactivity to negative images declines linearly with age, but responding to positive images is surprisingly age invariant across most of the adult life span.

  13. Carbon nanotube multi-electrode array chips for noninvasive real-time measurement of dopamine, action potentials, and postsynaptic potentials.

    Science.gov (United States)

    Suzuki, Ikuro; Fukuda, Mao; Shirakawa, Keiichi; Jiko, Hideyasu; Gotoh, Masao

    2013-11-15

    Multi-electrode arrays (MEAs) can be used for noninvasive, real-time, and long-term recording of electrophysiological activity and changes in the extracellular chemical microenvironment. Neural network organization, neuronal excitability, synaptic and phenotypic plasticity, and drug responses may be monitored by MEAs, but it is still difficult to measure presynaptic activity, such as neurotransmitter release, from the presynaptic bouton. In this study, we describe the development of planar carbon nanotube (CNT)-MEA chips that can measure both the release of the neurotransmitter dopamine as well as electrophysiological responses such as field postsynaptic potentials (fPSPs) and action potentials (APs). These CNT-MEA chips were fabricated by electroplating the indium-tin oxide (ITO) microelectrode surfaces. The CNT-plated ITO electrode exhibited electrochemical response, having much higher current density compared with the bare ITO electrode. Chronoamperometric measurements using these CNT-MEA chips detected dopamine at nanomolar concentrations. By placing mouse striatal brain slices on the CNT-MEA chip, we successfully measured synaptic dopamine release from spontaneous firings with a high S/N ratio of 62. Furthermore, APs and fPSPs were measured from cultured hippocampal neurons and slices with high temporal resolution and a 100-fold greater S/N ratio. Our CNT-MEA chips made it possible to measure neurotransmitter dopamine (presynaptic activities), postsynaptic potentials, and action potentials, which have a central role in information processing in the neuronal network. CNT-MEA chips could prove useful for in vitro studies of stem cell differentiation, drug screening and toxicity, synaptic plasticity, and pathogenic processes involved in epilepsy, stroke, and neurodegenerative diseases.

  14. T-type calcium channels consolidate tonic action potential output of thalamic neurons to neocortex.

    Science.gov (United States)

    Deleuze, Charlotte; David, François; Béhuret, Sébastien; Sadoc, Gérard; Shin, Hee-Sup; Uebele, Victor N; Renger, John J; Lambert, Régis C; Leresche, Nathalie; Bal, Thierry

    2012-08-29

    The thalamic output during different behavioral states is strictly controlled by the firing modes of thalamocortical neurons. During sleep, their hyperpolarized membrane potential allows activation of the T-type calcium channels, promoting rhythmic high-frequency burst firing that reduces sensory information transfer. In contrast, in the waking state thalamic neurons mostly exhibit action potentials at low frequency (i.e., tonic firing), enabling the reliable transfer of incoming sensory inputs to cortex. Because of their nearly complete inactivation at the depolarized potentials that are experienced during the wake state, T-channels are not believed to modulate tonic action potential discharges. Here, we demonstrate using mice brain slices that activation of T-channels in thalamocortical neurons maintained in the depolarized/wake-like state is critical for the reliable expression of tonic firing, securing their excitability over changes in membrane potential that occur in the depolarized state. Our results establish a novel mechanism for the integration of sensory information by thalamocortical neurons and point to an unexpected role for T-channels in the early stage of information processing.

  15. Relation between size of compound sensory or muscle action potentials, and length of nerve segment.

    Science.gov (United States)

    Kimura, J; Machida, M; Ishida, T; Yamada, T; Rodnitzky, R L; Kudo, Y; Suzuki, S

    1986-05-01

    In 24 median nerves from 12 healthy subjects, antidromic digital sensory potentials progressively diminished in size, averaging 40.4, 37.0, 30.7, and 23.9 microV X msec with stimulation at the palm, wrist, elbow, and axilla, respectively. In contrast, compound muscle action potentials changed minimally, measuring 19.4, 19.8, 19.0, and 18.2 mV X msec, respectively. Similar studies of the ulnar and radial nerves showed identical trends. Physiologic temporal dispersion can mimic conduction block of sensory nerves by summating the peaks of opposite polarity generated by fast- and slow-conducting axons. This type of cancellation affects muscle responses much less because motor unit potentials of longer duration superimpose nearly in phase, given the same latency shift as the sensory potentials.

  16. Antibacterial free fatty acids: activities, mechanisms of action and biotechnological potential.

    Science.gov (United States)

    Desbois, Andrew P; Smith, Valerie J

    2010-02-01

    Amongst the diverse and potent biological activities of free fatty acids (FFAs) is the ability to kill or inhibit the growth of bacteria. The antibacterial properties of FFAs are used by many organisms to defend against parasitic or pathogenic bacteria. Whilst their antibacterial mode of action is still poorly understood, the prime target of FFA action is the cell membrane, where FFAs disrupt the electron transport chain and oxidative phosphorylation. Besides interfering with cellular energy production, FFA action may also result from the inhibition of enzyme activity, impairment of nutrient uptake, generation of peroxidation and auto-oxidation degradation products or direct lysis of bacterial cells. Their broad spectrum of activity, non-specific mode of action and safety makes them attractive as antibacterial agents for various applications in medicine, agriculture and food preservation, especially where the use of conventional antibiotics is undesirable or prohibited. Moreover, the evolution of inducible FFA-resistant phenotypes is less problematic than with conventional antibiotics. The potential for commercial or biomedical exploitation of antibacterial FFAs, especially for those from natural sources, is discussed.

  17. 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.

  18. 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.

  19. 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.

  20. The potential for regional-scale bias in top-down CO2 flux estimates due to atmospheric transport errors

    Science.gov (United States)

    Miller, S. M.; Fung, I.; Liu, J.; Hayek, M. N.; Andrews, A. E.

    2014-09-01

    Estimates of CO2 fluxes that are based on atmospheric data rely upon a meteorological model to simulate atmospheric CO2 transport. These models provide a quantitative link between surface fluxes of CO2 and atmospheric measurements taken downwind. Therefore, any errors in the meteorological model can propagate into atmospheric CO2 transport and ultimately bias the estimated CO2 fluxes. These errors, however, have traditionally been difficult to characterize. To examine the effects of CO2 transport errors on estimated CO2 fluxes, we use a global meteorological model-data assimilation system known as "CAM-LETKF" to quantify two aspects of the transport errors: error variances (standard deviations) and temporal error correlations. Furthermore, we develop two case studies. In the first case study, we examine the extent to which CO2 transport uncertainties can bias CO2 flux estimates. In particular, we use a common flux estimate known as CarbonTracker to discover the minimum hypothetical bias that can be detected above the CO2 transport uncertainties. In the second case study, we then investigate which meteorological conditions may contribute to month-long biases in modeled atmospheric transport. We estimate 6 hourly CO2 transport uncertainties in the model surface layer that range from 0.15 to 9.6 ppm (standard deviation), depending on location, and we estimate an average error decorrelation time of ∼2.3 days at existing CO2 observation sites. As a consequence of these uncertainties, we find that CarbonTracker CO2 fluxes would need to be biased by at least 29%, on average, before that bias were detectable at existing non-marine atmospheric CO2 observation sites. Furthermore, we find that persistent, bias-type errors in atmospheric transport are associated with consistent low net radiation, low energy boundary layer conditions. The meteorological model is not necessarily more uncertain in these conditions. Rather, the extent to which meteorological uncertainties

  1. The potential for regional-scale bias in top-down CO2 flux estimates due to atmospheric transport errors

    Directory of Open Access Journals (Sweden)

    S. M. Miller

    2014-09-01

    Full Text Available Estimates of CO2 fluxes that are based on atmospheric data rely upon a meteorological model to simulate atmospheric CO2 transport. These models provide a quantitative link between surface fluxes of CO2 and atmospheric measurements taken downwind. Therefore, any errors in the meteorological model can propagate into atmospheric CO2 transport and ultimately bias the estimated CO2 fluxes. These errors, however, have traditionally been difficult to characterize. To examine the effects of CO2 transport errors on estimated CO2 fluxes, we use a global meteorological model-data assimilation system known as "CAM–LETKF" to quantify two aspects of the transport errors: error variances (standard deviations and temporal error correlations. Furthermore, we develop two case studies. In the first case study, we examine the extent to which CO2 transport uncertainties can bias CO2 flux estimates. In particular, we use a common flux estimate known as CarbonTracker to discover the minimum hypothetical bias that can be detected above the CO2 transport uncertainties. In the second case study, we then investigate which meteorological conditions may contribute to month-long biases in modeled atmospheric transport. We estimate 6 hourly CO2 transport uncertainties in the model surface layer that range from 0.15 to 9.6 ppm (standard deviation, depending on location, and we estimate an average error decorrelation time of ∼2.3 days at existing CO2 observation sites. As a consequence of these uncertainties, we find that CarbonTracker CO2 fluxes would need to be biased by at least 29%, on average, before that bias were detectable at existing non-marine atmospheric CO2 observation sites. Furthermore, we find that persistent, bias-type errors in atmospheric transport are associated with consistent low net radiation, low energy boundary layer conditions. The meteorological model is not necessarily more uncertain in these conditions. Rather, the extent to which meteorological

  2. FMRP regulates neurotransmitter release and synaptic information transmission by modulating action potential duration via BK channels.

    Science.gov (United States)

    Deng, Pan-Yue; Rotman, Ziv; Blundon, Jay A; Cho, Yongcheol; Cui, Jianmin; Cavalli, Valeria; Zakharenko, Stanislav S; Klyachko, Vitaly A

    2013-02-20

    Loss of FMRP causes fragile X syndrome (FXS), but the physiological functions of FMRP remain highly debatable. Here we show that FMRP regulates neurotransmitter release in CA3 pyramidal neurons by modulating action potential (AP) duration. Loss of FMRP leads to excessive AP broadening during repetitive activity, enhanced presynaptic calcium influx, and elevated neurotransmitter release. The AP broadening defects caused by FMRP loss have a cell-autonomous presynaptic origin and can be acutely rescued in postnatal neurons. These presynaptic actions of FMRP are translation independent and are mediated selectively by BK channels via interaction of FMRP with BK channel's regulatory β4 subunits. Information-theoretical analysis demonstrates that loss of these FMRP functions causes marked dysregulation of synaptic information transmission. FMRP-dependent AP broadening is not limited to the hippocampus, but also occurs in cortical pyramidal neurons. Our results thus suggest major translation-independent presynaptic functions of FMRP that may have important implications for understanding FXS neuropathology.

  3. Bepridil blockade of Ca2+-dependent action potentials in vascular smooth muscle of dog coronary artery.

    Science.gov (United States)

    Harder, D R; Sperelakis, N

    1981-01-01

    The effect of the new vasodilatory and antianginal compound, bepridil (CERM-1978), was examined on the electrical activity of the vascular smooth muscle of isolated dog coronary arteries. Tetraethylammonium (10 mM) was used to induce excitability in the muscle in the form of Ca2+-dependent overshooting action potentials, whose inward current is carried almost exclusively by Ca2+ ion through voltage-dependent slow channels. Bepridil (5 X 10(-7)--1 X 10(--5) M) produced a dose-dependent depression of the rate of rise and amplitude of these Ca2+ spikes. Complete blockade of the action potentials occurred at 1 X 10(-5) M bepridil. These effects of bepridil were antagonized by elevation of external Ca2+ concentration ([CA]o). The effects of bepridil were substantially reversed by washout after about 30 min. Bepridil (10(-5) M) also produced a small but significant (p less than 0.05) increase in resting membrane resistance (input resistance increased from a mean of 10.1 to 12.4 m omega), accompanied by a small but significant (p less than 0.05) depolarization of 6 mV (from a mean of --51 to --45 mV). These latter effects are consistent with a diminution of the resting K+ conductance (gK) by bepridil. It is concluded that the vasodilatory and antianginal properties of bepridil may be explained by the action of this drug in depressing and blocking the Ca2+ influx into the cells, presumably by acting directly on the voltage-dependent slow channels in the cell membrane, and thereby lowering [Ca]i and thus the degree of contraction. Bepridil has Ca2+-antagonistic (or Ca2+ entry blocking or slow channel blocking) properties much like verapamil, but it is somewhat less potent than verapamil in this action (i.e., complete blockade occurred at 10(-5) M bepridil vs. 2 X 10(-6) M verapamil).

  4. 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.

  5. High-speed digital video imaging system to record cardiac action potentials

    Science.gov (United States)

    Mishima, Akira; Arafune, Tatsuhiko; Masamune, Ken; Sakuma, Ichiro; Dohi, Takeyoshi; Shibata, Nitaro; Honjo, Haruo; Kodama, Itsuo

    2001-01-01

    A new digital video imaging system was developed and its performance was evaluated to analyze the spiral wave dynamics during polymorphic ventricular tachycardia (PVT) with high spatio-temporal resolution (1 ms, 0.1 mm). The epicardial surface of isolated rabbit heart stained with di- 4-ANEPPS was illuminated by 72 high-power bluish-green light emitting diodes (BGLED: (lambda) 0 500 nm, 10mw). The emitted fluorescence image (256x256 pixels) passing through a long-pass filter ((lambda) c 660nm) was monitored by a high-speed digital video camera recorder (FASTCAM-Ultima- UV3, Photron) at 1125 fps. The data stored in DRAM were processed by PC for background subtraction. 2D images of excitation wave and single-pixel action potentials at target sites during PVT induced by DC shocks (S2: 10 ms, 20 V) were displayed for 4.5 s. The wave form quality is high enough to observe phase 0 upstroke and to identify repolarization timing. Membrane potentials at the center of spiral were characterized by double-peak or oscillatory depolarization. Singular points during PVT were obtained from isophase mapping. Our new digital video-BGLED system has an advantage over previous ones for more accurate and longer time action potential analysis during spiral wave reentry.

  6. The Effects of Action Potential Stimulation on Pain, Swelling and Function of Patients with Knee Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Razieh Sepehri

    2012-06-01

    Full Text Available Background: Knee osteoarthritis (OA is one of the most prevalent joint diseases. Electrical muscle stimulation is effective to improve its symptoms. Today, action potential stimulation (APS with various currents and periods is used to treat OA. This study aims at analyzing the effect of action potential stimulation in improving knee OA symptoms. Materials and Methods: In this clinical trial, patients with mild to moderate knee OA divided randomly in two groups each had 15 people. Along with the conventional exercises of physiotherapy, one group received 16 minutes action potential stimulation with the lowest intensity (sensible; but the other group besides receiving the conventional exercises of physiotherapy was connected into a plugged off machine for 16 minutes. Certain variables were measured and recorded four times. Results: Comparing the variables before and after intervention did not show any meaningful difference between the two groups. But within group, pain with p=0.0001 showed a meaningful decrease. Decreasing of swelling (inflammation in group 1 and 2 was meaningful with p<0.001 and p<0.001, respectively. For group 1, knee flexion range was improved meaningfully between first and fourth times as p<0.031, but it was not meaningful for group 2. Duration of 50 meters walking and step up and down from three steps significantly decreased in both groups. Conclusion: Although there was no significant difference in variables between two groups, but within both groups’ pain and swelling decreased and functional ability increased, thus, it can be concluded that type of APS does not play a key role in treating knee OA.

  7. Carbon Monoxide Effects onHuman Ventricle Action PotentialAssessed by Mathematical Simulations

    Directory of Open Access Journals (Sweden)

    Beatriz eTrenor

    2013-10-01

    Full Text Available 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 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 recently reported changes in CO-induced ion channel activity and intracellular signalling 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 Ca2+ 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.

  8. 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.

  9. Effects of Potassium Currents upon Action Potential of Cardiac Cells Exposed to External Electric fields

    Institute of Scientific and Technical Information of China (English)

    An-Ying Zhang; Xiao-Feng Pang

    2008-01-01

    Previous studies show that exposure to high-voltage electric fields would influence the electro cardiogram both in experimental animate and human beings. The effects of the external electric fields upon action potential of cardiac cells are studied in this paper based on the dynamical model, LR91. Fourth order Runger-Kuta is used to analyze the change of potassium ion channels exposed to external electric fields in detail. Results indicate that external electric fields could influence the current of potassium ion by adding an induced component voltage on membrane. This phenomenon might be one of the reasons of heart rate anomaly under the high-voltage electric fields.

  10. The Healthy Bus project in Denmark: need for an action potential assessment.

    Science.gov (United States)

    Poulsen, Kjeld B

    2004-06-01

    Research over the last 50 years has repeatedly documented that bus drivers are exposed to several physical and psychological risk factors, which are associated with health problems in the form of heart, musculo-skeletal and stomach disease, and increased coronary mortality. So why has there been little action to improve the situation when it is so obviously indicated by such assessments? This article describes the long and complex process that has made it possible to launch almost 200 interventions among the 3500 municipal bus drivers in Copenhagen. Using a participative action research design, new evidence was gathered by broadening the traditional work environmental scope to lifestyle, health issues and private matters. Comparing this updated needs assessment with a national reference population, it was found that drivers were often still worse off. Again, simply presenting new evidence did not seem to lead to changes and further work is needed to empower the stakeholders so that they can commit to start making effective interventions. It is concluded that every needs assessment has to be supplemented with an evaluation of the action potential.

  11. Too Reliable to Be True? Response Bias as a Potential Source of Inflation in Paper-and-Pencil Questionnaire Reliability

    Directory of Open Access Journals (Sweden)

    Eyal Peer

    2011-06-01

    Full Text Available When respondents answer paper-and-pencil (PP questionnaires, they sometimes modify their responses to correspond to previously answered items. As a result, this response bias might artificially inflate the reliability of PP questionnaires. We compared the internal consistency of PP questionnaires to computerized questionnaires that presented a different number of items on a computer screen simultaneously. Study 1 showed that a PP questionnaire's internal consistency was higher than that of the same questionnaire presented on a computer screen with one, two or four questions per screen. Study 2 replicated these findings to show that internal consistency was also relatively high when all questions were shown on one screen. This suggests that the differences found in Study 1 were not due to the difference in presentation medium. Thus, this paper suggests that reliability measures of PP questionnaires might be inflated because of a response bias resulting from participants cross-checking their answers against ones given to previous questions.

  12. Electrical Identification and Selective Microstimulation of Neuronal Compartments Based on Features of Extracellular Action Potentials

    Science.gov (United States)

    Radivojevic, Milos; Jäckel, David; Altermatt, Michael; Müller, Jan; Viswam, Vijay; Hierlemann, Andreas; Bakkum, Douglas J.

    2016-08-01

    A detailed, high-spatiotemporal-resolution characterization of neuronal responses to local electrical fields and the capability of precise extracellular microstimulation of selected neurons are pivotal for studying and manipulating neuronal activity and circuits in networks and for developing neural prosthetics. Here, we studied cultured neocortical neurons by using high-density microelectrode arrays and optical imaging, complemented by the patch-clamp technique, and with the aim to correlate morphological and electrical features of neuronal compartments with their responsiveness to extracellular stimulation. We developed strategies to electrically identify any neuron in the network, while subcellular spatial resolution recording of extracellular action potential (AP) traces enabled their assignment to the axon initial segment (AIS), axonal arbor and proximal somatodendritic compartments. Stimulation at the AIS required low voltages and provided immediate, selective and reliable neuronal activation, whereas stimulation at the soma required high voltages and produced delayed and unreliable responses. Subthreshold stimulation at the soma depolarized the somatic membrane potential without eliciting APs.

  13. 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.

  14. Increase in action potential duration and inhibition of the delayed rectifier outward current IK by berberine in cat ventricular myocytes.

    OpenAIRE

    Sánchez-Chapula, J.

    1996-01-01

    1. In the present work, the effects of the antiarrhythmic drug, berberine, on action potential and ionic currents of cat ventricular myocytes were studied. 2. Berberine prolonged action potential duration in cat ventricular myocytes without altering other variables of the action potential. 3. The drug at concentrations of 0.3-30 microM blocked only the delayed rectifier (IK) current with an IC50 = 4.1 microM. Berberine produced a tonic block and a phasic block that was increased with the dura...

  15. Intergroup bias.

    Science.gov (United States)

    Hewstone, Miles; Rubin, Mark; Willis, Hazel

    2002-01-01

    This chapter reviews the extensive literature on bias in favor of in-groups at the expense of out-groups. We focus on five issues and identify areas for future research: (a) measurement and conceptual issues (especially in-group favoritism vs. out-group derogation, and explicit vs. implicit measures of bias); (b) modern theories of bias highlighting motivational explanations (social identity, optimal distinctiveness, uncertainty reduction, social dominance, terror management); (c) key moderators of bias, especially those that exacerbate bias (identification, group size, status and power, threat, positive-negative asymmetry, personality and individual differences); (d) reduction of bias (individual vs. intergroup approaches, especially models of social categorization); and (e) the link between intergroup bias and more corrosive forms of social hostility.

  16. A critical examination of spatial biases between MODIS and MISR aerosol products – application for potential AERONET deployment

    Directory of Open Access Journals (Sweden)

    T. F. Eck

    2011-12-01

    Full Text Available AErosol RObotic NETwork (AERONET data are the primary benchmark for evaluating satellite-retrieved aerosol properties. However, despite its extensive coverage, the representativeness of the AERONET data is rarely discussed. Indeed, many studies have shown that satellite retrieval biases have a significant degree of spatial correlation that may be problematic for higher-level processes or inverse-emissions-modeling studies. To consider these issues and evaluate relative performance in regions of few surface observations, cross-comparisons between the Aerosol Optical Depth (AOD products of operational MODIS Collection 5.1 Dark Target (DT and operational MODIS Collection 5.1 Deep Blue (DB with MISR version 22 were conducted. Through such comparisons, we can observe coherent spatial features of the AOD bias while sidestepping the full analysis required for determining when or where either retrieval is more correct. We identify regions where MODIS to MISR AOD ratios were found to be above 1.4 and below 0.7. Regions where lower boundary condition uncertainty is likely to be a dominant factor include portions of Western North America, the Andes mountains, Saharan Africa, the Arabian Peninsula, and Central Asia. Similarly, microphysical biases may be an issue in South America, and specific parts of Southern Africa, India Asia, East Asia, and Indonesia. These results help identify high-priority locations for possible future deployments of both in situ and ground based remote sensing measurements. The Supplement includes a kml file.

  17. A Critical Examination of Spatial Biases Between MODIS and MISR Aerosol Products - Application for Potential AERONET Deployment

    Science.gov (United States)

    Shi, Y.; Zhang, J.; Reid, J. S.; Hyer, E. J.; Eck, T. F.; Holben, B. N.; Kahn, R. A.

    2011-01-01

    AErosol RObotic NETwork (AERONET) data are the primary benchmark for evaluating satellite-retrieved aerosol properties. However, despite its extensive coverage, the representativeness of the AERONET data is rarely discussed. Indeed, many studies have shown that satellite retrieval biases have a significant degree of spatial correlation that may be problematic for higher-level processes or inverse-emissions-modeling studies. To consider these issues and evaluate relative performance in regions of few surface observations, cross-comparisons between the Aerosol Optical Depth (AOD) products of operational MODIS Collection 5.1 Dark Target (DT) and operational MODIS Collection 5.1 Deep Blue (DB) with MISR version 22 were conducted. Through such comparisons, we can observe coherent spatial features of the AOD bias while side-stepping the full analysis required for determining when or where either retrieval is more correct. We identify regions where MODIS to MISR AOD ratios were found to be above 1.4 and below 0.7. Regions where lower boundary condition uncertainty is likely to be a dominant factor include portions of Western North America, the Andes mountains, Saharan Africa, the Arabian Peninsula, and Central Asia. Similarly, microphysical biases may be an issue in South America, and specific parts of Southern Africa, India Asia, East Asia, and Indonesia. These results help identify high-priority locations for possible future deployments of both in situ and ground based remote sensing measurements. The Supplement includes a km1 file.

  18. 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.

  19. From damage response to action potentials: early evolution of neural and contractile modules in stem eukaryotes.

    Science.gov (United States)

    Brunet, Thibaut; Arendt, Detlev

    2016-01-05

    Eukaryotic cells convert external stimuli into membrane depolarization, which in turn triggers effector responses such as secretion and contraction. Here, we put forward an evolutionary hypothesis for the origin of the depolarization-contraction-secretion (DCS) coupling, the functional core of animal neuromuscular circuits. We propose that DCS coupling evolved in unicellular stem eukaryotes as part of an 'emergency response' to calcium influx upon membrane rupture. We detail how this initial response was subsequently modified into an ancient mechanosensory-effector arc, present in the last eukaryotic common ancestor, which enabled contractile amoeboid movement that is widespread in extant eukaryotes. Elaborating on calcium-triggered membrane depolarization, we reason that the first action potentials evolved alongside the membrane of sensory-motile cilia, with the first voltage-sensitive sodium/calcium channels (Nav/Cav) enabling a fast and coordinated response of the entire cilium to mechanosensory stimuli. From the cilium, action potentials then spread across the entire cell, enabling global cellular responses such as concerted contraction in several independent eukaryote lineages. In animals, this process led to the invention of mechanosensory contractile cells. These gave rise to mechanosensory receptor cells, neurons and muscle cells by division of labour and can be regarded as the founder cell type of the nervous system. © 2015 The Authors.

  20. The characteristics of action potential and nonselective cation current of cardiomyocytes in rabbit superior vena cava

    Institute of Scientific and Technical Information of China (English)

    WANG Pan; YANG XinChun; LIU XiuLan; BAO RongFeng; LIU TaiFeng

    2008-01-01

    As s special focus in initiating and maintaining atrial fibrillation (AF), cardiomyocytes in superior vena cavs (SVC) have distinctive electrophysiological characters. In this study, we found that comparing with the right atrial (RA) cardiomyoctyes, the SVC cardiomyoctyes had longer APD90 at the different basic cycle lengths; the conduction block could be observed on both RA and SVC cardiomyoctyes. A few of SVC cardiomyoctyes showed slow response action potentials with automatic activity and some others showed early afterdepolarization (EAD) spontaneously. Further more, we found that there are nonselective cation current (INs) in both SVC and RA cardiomyocytes. The peak density of INs in SVC cardiomyocytes was smaller than that in RA cardiomyocytes. Removal of extracellular divalent cation and glucose could increase INs in SVC cardiomyocytes. The agonist or the antagonist of INs may increase or decrease APD. To sum up, some SVC cardiomyocytes possess the ability of spontaneous activity; the difference of transmembrane action potentials between SVC and RA cardiomyocytes is partly because of the different density of INs between them; the agonist or the antagonist of INs can increase or decrease APD leading to the enhancement or reduction of EAD genesis in SVC cardiomyocytes. INs in rabbit myocytes is fairly similar to TRPC3 current in electrophysiological property, which might play an important role in the mechanisms of AF.

  1. Applications of control theory to the dynamics and propagation of cardiac action potentials.

    Science.gov (United States)

    Muñoz, Laura M; Stockton, Jonathan F; Otani, Niels F

    2010-09-01

    Sudden cardiac arrest is a widespread cause of death in the industrialized world. Most cases of sudden cardiac arrest are due to ventricular fibrillation (VF), a lethal cardiac arrhythmia. Electrophysiological abnormalities such as alternans (a beat-to-beat alternation in action potential duration) and conduction block have been suspected to contribute to the onset of VF. This study focuses on the use of control-systems techniques to analyze and design methods for suppressing these precursor factors. Control-systems tools, specifically controllability analysis and Lyapunov stability methods, were applied to a two-variable Karma model of the action-potential (AP) dynamics of a single cell, to analyze the effectiveness of strategies for suppressing AP abnormalities. State-feedback-integral (SFI) control was then applied to a Purkinje fiber simulated with the Karma model, where only one stimulating electrode was used to affect the system. SFI control converted both discordant alternans and 2:1 conduction block back toward more normal patterns, over a wider range of fiber lengths and pacing intervals compared with a Pyragas-type chaos controller. The advantages conferred by using feedback from multiple locations in the fiber, and using integral (i.e., memory) terms in the controller, are discussed.

  2. Supernormal Conduction and Suppression of Spatial Discord in Alternans of Cardiac Action Potentials

    Directory of Open Access Journals (Sweden)

    Linyuan eJing

    2016-01-01

    Full Text Available Spatially discordant alternans (DA of action potential durations (APD is thought to be more pro-arrhythmic than concordant alternans. Super normal conduction (SNC has been reported to suppress formation of DA. An increase in conduction velocity (CV as activation rate increases, i.e. a negative CV restitution, is widely considered as hallmark of SNC. Our aim in this study is to show that it is not an increase in CV for faster rates that prevents formation of DA, rather, it is the ratio of the CV for the short relative to the long activation that is critical in DA suppression. To illustrate this subtlety, we simulated this phenomenon using two approaches; (1 by using the standard, i.e. S1S2 protocol to quantify restitution and disabling the slow inactivation gate j of the sodium current (INa, and (2 by using the dynamic, i.e. S1S1 protocol for quantification of restitution and increasing INa at different cycle lengths (CL. Even though both approaches produced similar CV restitution curves, DA was suppressed only during the first approach, where the CV of the short of the long-short action potential (AP pattern was selectively increased. These results show that negative CV restitution, which is considered characteristic of SNC, per se, is not causal in suppressing DA, rather, the critical factor is a change in the ratio of the velocities of the short and the long APs.

  3. Supernormal Conduction and Suppression of Spatially Discordant Alternans of Cardiac Action Potentials.

    Science.gov (United States)

    Jing, Linyuan; Agarwal, Anuj; Patwardhan, Abhijit

    2015-01-01

    Spatially discordant alternans (DA) of action potential durations (APD) is thought to be more pro-arrhythmic than concordant alternans. Super normal conduction (SNC) has been reported to suppress formation of DA. An increase in conduction velocity (CV) as activation rate increases, i.e., a negative CV restitution, is widely considered as hallmark of SNC. Our aim in this study is to show that it is not an increase in CV for faster rates that prevents formation of DA, rather, it is the ratio of the CV for the short relative to the long activation that is critical in DA suppression. To illustrate this subtlety, we simulated this phenomenon using two approaches; (1) by using the standard, i.e., S1S2 protocol to quantify restitution and disabling the slow inactivation gate j of the sodium current (INa), and (2) by using the dynamic, i.e., S1S1 protocol for quantification of restitution and increasing INa at different cycle lengths (CL). Even though both approaches produced similar CV restitution curves, DA was suppressed only during the first approach, where the CV of the short of the long-short action potential (AP) pattern was selectively increased. These results show that negative CV restitution, which is considered characteristic of SNC, per se, is not causal in suppressing DA, rather, the critical factor is a change in the ratio of the velocities of the short and the long APs.

  4. Effects of acoustic noise on the auditory nerve compound action potentials evoked by electric pulse trains.

    Science.gov (United States)

    Nourski, Kirill V; Abbas, Paul J; Miller, Charles A; Robinson, Barbara K; Jeng, Fuh-Cherng

    2005-04-01

    This study investigated the effects of acoustic noise on the auditory nerve compound action potentials in response to electric pulse trains. Subjects were adult guinea pigs, implanted with a minimally invasive electrode to preserve acoustic sensitivity. Electrically evoked compound action potentials (ECAP) were recorded from the auditory nerve trunk in response to electric pulse trains both during and after the presentation of acoustic white noise. Simultaneously presented acoustic noise produced a decrease in ECAP amplitude. The effect of the acoustic masker on the electric probe was greatest at the onset of the acoustic stimulus and it was followed by a partial recovery of the ECAP amplitude. Following cessation of the acoustic noise, ECAP amplitude recovered over a period of approximately 100-200 ms. The effects of the acoustic noise were more prominent at lower electric pulse rates (interpulse intervals of 3 ms and higher). At higher pulse rates, the ECAP adaptation to the electric pulse train alone was larger and the acoustic noise, when presented, produced little additional effect. The observed effects of noise on ECAP were the greatest at high electric stimulus levels and, for a particular electric stimulus level, at high acoustic noise levels.

  5. The use of sensory action potential to evaluate inferior alveolar nerve damage after orthognathic surgery.

    Science.gov (United States)

    Calabria, Francesca; Sellek, Lucy; Gugole, Fabio; Trevisiol, Lorenzo; Trevisol, Lorenzo; Bertolasi, Laura; D'Agostino, Antonio

    2013-03-01

    To assess and monitor the common event of neurosensory disturbance to the inferior alveolar nerve (IAN) after bilateral sagittal split osteotomy, we used clinical sensory tests and neurophysiologic test sensory action potentials. The diagnostic value of these tests was evaluated by comparing them with the degree of nerve damage reported by patients. Fourteen patients undergoing bilateral sagittal split osteotomy were analyzed preoperatively and 2 years postoperatively. Patients were evaluated bilaterally for positive and negative symptoms: light touch sensation, paraesthesia, hyperesthesia, and dysaesthesia; a "sensation score" was then calculated for each patient. Patients were also asked if they would be willing to repeat the procedure knowing the sensation loss they had now. Next, the right and left IAN were evaluated using sensory action potential and correlated with the other results. Before surgery, the medium latency difference between left and right was lower compared with postsurgery, with all patients having some deficit. The reduction in medium amplitude of 67% after the intervention was statistically significant. The frequency of abnormal findings in the electrophysiologic tests indicating IAN injury correlated with subjective sensory alteration. All patients said that they would repeat the surgery. Electrophysiologic testing is recommended for the evaluation of nerve dysfunction and seems a sensitive method for accurately assessing postsurgical nerve conduction.

  6. Modulation of action potential and calcium signaling by levetiracetam in rat sensory neurons.

    Science.gov (United States)

    Ozcan, Mete; Ayar, Ahmet

    2012-06-01

    Levetiracetam (LEV), a new anticonvulsant agent primarily used to treat epilepsy, has been used in pain treatment but the cellular mechanism of this action remains unclear. This study aimed to investigate effects of LEV on the excitability and membrane depolarization-induced calcium signaling in isolated rat sensory neurons using the whole-cell patch clamp and fura 2-based ratiometric Ca(2+)-imaging techniques. Dorsal root ganglia (DRG) were excised from neonatal rats, and cultured following enzymatic and mechanical dissociation. Under current clamp conditions, acute application of LEV (30 µM, 100 µM and 300 µM) significantly increased input resistance and caused the membrane to hyperpolarize from resting membrane potential in a dose-dependent manner. Reversal potentials of action potential (AP) after hyperpolarising amplitudes were shifted to more negative, toward to potassium equilibrium potentials, after application of LEV. It also caused a decrease in number of APs in neurons fired multiple APs in response to prolonged depolarization. Fura-2 fluorescence Ca(2+) imaging protocols revealed that HiK(+) (30 mM)-induced intracellular free Ca(2+) ([Ca(2+)](i)) was inhibited to 97.8 ± 4.6% (n = 17), 92.6 ± 4.8% (n = 17, p < 0.01) and 89.1 ± 5.1% (n = 18, p < 0.01) after application of 30 µM, 100 µM and 300 µM LEV (respectively), without any significant effect on basal levels of [Ca(2+)](i). This is the first evidence for the effect of LEV on the excitability of rat sensory neurons through an effect which might involve activation of potassium channels and inhibition of entry of Ca(2+), providing new insights for cellular mechanism(s) of LEV in pain treatment modalities.

  7. Whey protein potentiates the intestinotrophic action of glucagon-like peptide-2 in parenterally fed rats.

    Science.gov (United States)

    Liu, Xiaowen; Murali, Sangita G; Holst, Jens J; Ney, Denise M

    2009-11-01

    Glucagon-like peptide-2 (GLP-2) is a nutrient-regulated intestinotrophic hormone derived from proglucagon in the distal intestine. Enteral nutrients (EN) potentiate the action of GLP-2 to reverse parenteral nutrition (PN)-induced mucosal hypoplasia. The objective was to determine what enteral 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 and gain of body weight, and improved feed efficiency compared with PN+GLP-2 alone. EN induced greater ileal proglucagon expression, increased plasma concentration of bioactive GLP-2 by 35%, and reduced plasma dipeptidyl peptidase IV (DPP-IV) activity compared with PN+GLP-2 alone, P 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 was associated with decreased DPP-IV activity in ileum and colon compared with casein, soy, or PN+GLP-2 alone, P whey protein potentiates the action of GLP-2 to reverse PN-induced mucosal hypoplasia in association with decreased intestinal DPP-IV activity.

  8. Comparative investigations of manual action representations: evidence that chimpanzees represent the costs of potential future actions involving tools.

    Science.gov (United States)

    Frey, Scott H; Povinelli, Daniel J

    2012-01-12

    The ability to adjust one's ongoing actions in the anticipation of forthcoming task demands is considered as strong evidence for the existence of internal action representations. Studies of action selection in tool use reveal that the behaviours that we choose in the present moment differ depending on what we intend to do next. Further, they point to a specialized role for mechanisms within the human cerebellum and dominant left cerebral hemisphere in representing the likely sensory costs of intended future actions. Recently, the question of whether similar mechanisms exist in other primates has received growing, but still limited, attention. Here, we present data that bear on this issue from a species that is a natural user of tools, our nearest living relative, the chimpanzee. In experiment 1, a subset of chimpanzees showed a non-significant tendency for their grip preferences to be affected by anticipation of the demands associated with bringing a tool's baited end to their mouths. In experiment 2, chimpanzees' initial grip preferences were consistently affected by anticipation of the forthcoming movements in a task that involves using a tool to extract a food reward. The partial discrepancy between the results of these two studies is attributed to the ability to accurately represent differences between the motor costs associated with executing the two response alternatives available within each task. These findings suggest that chimpanzees are capable of accurately representing the costs of intended future actions, and using those predictions to select movements in the present even in the context of externally directed tool use.

  9. Typical gray matter axons in mammalian brain fail to conduct action potentials faithfully at fever-like temperatures.

    Science.gov (United States)

    Pekala, Dobromila; Szkudlarek, Hanna; Raastad, Morten

    2016-10-01

    We studied the ability of typical unmyelinated cortical axons to conduct action potentials at fever-like temperatures because fever often gives CNS symptoms. We investigated such axons in cerebellar and hippocampal slices from 10 to 25 days old rats at temperatures between 30 and 43°C. By recording with two electrodes along axonal pathways, we confirmed that the axons were able to initiate action potentials, but at temperatures >39°C, the propagation of the action potentials to a more distal recording site was reduced. This temperature-sensitive conduction may be specific for the very thin unmyelinated axons because similar recordings from myelinated CNS axons did not show conduction failures. We found that the conduction fidelity improved with 1 mmol/L TEA in the bath, probably due to block of voltage-sensitive potassium channels responsible for the fast repolarization of action potentials. Furthermore, by recording electrically activated antidromic action potentials from the soma of cerebellar granule cells, we showed that the axons failed less if they were triggered 10-30 msec after another action potential. This was because individual action potentials were followed by a depolarizing after-potential, of constant amplitude and shape, which facilitated conduction of the following action potentials. The temperature-sensitive conduction failures above, but not below, normal body temperature, and the failure-reducing effect of the spike's depolarizing after-potential, are two intrinsic mechanisms in normal gray matter axons that may help us understand how the hyperthermic brain functions. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  10. The use of interim data and Data Monitoring Committee recommendations in randomized controlled trial reports: frequency, implications and potential sources of bias

    Directory of Open Access Journals (Sweden)

    Hampton John

    2008-03-01

    Full Text Available Abstract Background Interim analysis of accumulating trial data is important to protect participant safety during randomized controlled trials (RCTs. Data Monitoring Committees (DMCs often undertake such analyses, but their widening role may lead to extended use of interim analysis or recommendations that could potentially bias trial results. Methods Systematic search of eight major publications: Annals of Internal Medicine, BMJ, Circulation, CID, JAMA, JCO, Lancet and NEJM, including all randomised controlled trials (RCTs between June 2000 and May 2005 to identify RCTs that reported use of interim analysis, with or without DMC involvement. Recommendations made by the DMC or based on interim analysis were identified and potential sources of bias assessed. Independent double data extraction was performed on all included trials. Results We identified 1772 RCTs, of which 470 (27%; 470/1772 reported the use of a DMC and a further 116 (7%; 116/1772 trials reported some form of interim analysis without explicit mention of a DMC. There were 28 trials (24 with a formal DMC, randomizing a total of 79396 participants, identified as recommending changes to the trial that may have lead to biased results. In most of these, some form of sample size re-estimation was recommended with four trials also reporting changes to trial endpoints. The review relied on information reported in the primary publications and methods papers relating to the trials, higher rates of use may have occurred but not been reported. Conclusion The reported use of interim analysis and DMCs in clinical trials has been increasing in recent years. It is reassuring that in most cases recommendations were made in the interest of participant safety. However, in practice, recommendations that may lead to potentially biased trial results are being made.

  11. 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

    2015-07-01

    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.

  12. 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.

  13. Potential bias due to outcome-related loss to follow-up in cohort studies on incidence of drug injection: systematic review and meta-analysis.

    Science.gov (United States)

    Sordo, Luis; Bravo, Maria J; Barrio, Gregorio; Indave, B Iciar; Degenhardt, Louisa; Pastor-Barriuso, Roberto

    2015-08-01

    A systematic review and meta-analysis were conducted to synthesize results from cohort studies on initiation into drug injection among vulnerable populations, to quantify heterogeneity in the estimated incidence rates of drug injection and to identify potential sources of heterogeneity and bias. MEDLINE, EMBASE, PsycINFO and LILACS were searched for relevant studies published between 1980 and 2012. Investigators independently reviewed studies for inclusion, retrieved information on baseline population characteristics and follow-up features and assessed study quality. Study-specific incidence rates of drug injection were calculated as the number of new injectors divided by the person-years at risk. The I(2) statistic was used to quantify heterogeneity in incidence rates across studies, and random-effects meta-regression models were used to identify determinants of heterogeneity and bias. Nine cohorts totalling 1843 participants met the inclusion criteria, with individual sample sizes of 70-415 participants and follow-up lengths of 6 months-3.4 years. The incidence of drug injection varied widely, from 2.1 to 24.2 cases per 100 person-years. The strong between-study heterogeneity (I(2)  = 90%, Pcohort studies on drug injection initiation. Low retention rates and potential for downward selection bias in cohort studies on drug injection initiation are caused primarily by greater loss to follow-up among individuals at higher risk of starting injection, compared with other participants. © 2015 Society for the Study of Addiction.

  14. High Threshold, Proximal Initiation, and Slow Conduction Velocity of Action Potentials in Dentate Granule Neuron Mossy Fibers

    OpenAIRE

    Kress, Geraldine J.; Dowling, Margaret J.; Meeks, Julian P.; Mennerick, Steven

    2008-01-01

    Dentate granule neurons give rise to some of the smallest unmyelinated fibers in the mammalian CNS, the hippocampal mossy fibers. These neurons are also key regulators of physiological and pathophysiological information flow through the hippocampus. We took a comparative approach to studying mossy fiber action potential initiation and propagation in hippocampal slices from juvenile rats. Dentate granule neurons exhibited axonal action potential initiation significantly more proximal than CA3 ...

  15. Action potential-simulated weak electric fields can directly initiate myelination

    Institute of Scientific and Technical Information of China (English)

    Lei Liu; Shifu Zhao; Haiming Wang

    2008-01-01

    BACKGROUND: Myelination is a process whereby glial cells identify, adhere, wrap and enclose axons to form a spiral myelin sheath.OBJECTIVE: To investigate the effects of action potential-simulated weak electric fields on myelination in the central nervous system.DESIGN AND SETTING: This single-sample observation study was performed at the 324 Hospital of Chinese PLA.MATERIALS: Two 5 μm carbon fibers were provided by the Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. One Sprague Dawley rat, aged 1 day, was used.METHODS: Cerebral cortex was harvested from the rat to prepare a suspension [(1-2)×105/mL] containing neurons and glial cells. To simulate the axon, carbon fibers were placed at the bottom of the neuron-glial cell coculture dish, and were electrified with a single phase square wave current, 1×10-2, 1×10-3, 1×10-4, and 1×10-5 seconds, 1 Hz, 40 mV, and 10 μA, 30 minutes each, once aday for 10 consecutive days to simulate weak negative electric fields during action potential conduction.MAIN OUTCOME MEASURES: Glial cell growth and wrapping of carbon fibers were observed by phase contrast microscopy and immunohistochemistry.RESULTS: On culture day 7, cell groups were found to adhere to negative carbon fibers in the 1×10-3 seconds square wave group. Cell membrane-like substances grew out of cell groups, wrapped the carbon fibers, and stretched to the ends of carbon fibers. Only some small and round cells close to negative carbon fibers were found on culture day 12. In the 1×10-4 and 1×10-3 seconds square wave groups, the negative carbon fibers were wrapped by oligodendrocytes or their progenitor cells.CONCLUSION: The local negative electric field which is generated by action potentials at 1×(10-4-10-3)seconds, 40 mV can directly initiate and participate in myelination in the central nervous system.

  16. Modulation by K+ channels of action potential-evoked intracellular Ca2+ concentration rises in rat cerebellar basket cell axons.

    Science.gov (United States)

    Tan, Y P; Llano, I

    1999-10-01

    1. Action potential-evoked [Ca2+]i rises in basket cell axons of rat cerebellar slices were studied using two-photon laser scanning microscopy and whole-cell recording, to identify the K+ channels controlling the shape of the axonal action potential. 2. Whole-cell recordings of Purkinje cell IPSCs were used to screen K+ channel subtypes which could contribute to axonal repolarization. alpha-Dendrotoxin, 4-aminopyridine, charybdotoxin and tetraethylammonium chloride increased IPSC rate and/or amplitude, whereas iberiotoxin and apamin failed to affect the IPSCs. 3. The effects of those K+ channel blockers that enhanced transmitter release on the [Ca2+]i rises elicited in basket cell axons by action potentials fell into three groups: 4-aminopyridine strongly increased action potential-evoked [Ca2+]i; tetraethylammonium and charybdotoxin were ineffective alone but augmented the effects of 4-aminopyridine; alpha-dendrotoxin had no effect. 4. We conclude that cerebellar basket cells contain at least three pharmacologically distinct K+ channels, which regulate transmitter release through different mechanisms. 4-Aminopyridine-sensitive, alpha-dendrotoxin-insensitive K+ channels are mainly responsible for repolarization in basket cell presynaptic terminals. K+ channels blocked by charybdotoxin and tetraethylammonium have a minor role in repolarization. alpha-Dendrotoxin-sensitive channels are not involved in shaping the axonal action potential waveform. The two last types of channels must therefore exert control of synaptic activity through a pathway unrelated to axonal action potential broadening.

  17. FMRP Regulates Neurotransmitter Release and Synaptic Information Transmission by Modulating Action Potential Duration via BK channels

    Science.gov (United States)

    Deng, Pan-Yue; Rotman, Ziv; Blundon, Jay A.; Cho, Yongcheol; Cui, Jianmin; Cavalli, Valeria; Zakharenko, Stanislav S.; Klyachko, Vitaly A.

    2013-01-01

    SUMMARY Loss of FMRP causes Fragile X syndrome (FXS), but the physiological functions of FMRP remain highly debatable. Here we show that FMRP regulates neurotransmitter release in CA3 pyramidal neurons by modulating action potential (AP) duration. Loss of FMRP leads to excessive AP broadening during repetitive activity, enhanced presynaptic calcium influx and elevated neurotransmitter release. The AP broadening defects caused by FMRP loss have a cell-autonomous presynaptic origin and can be acutely rescued in postnatal neurons. These presynaptic actions of FMRP are translation-independent and are mediated selectively by BK channels via interaction of FMRP with BK channel’s regulatory β4 subunits. Information-theoretical analysis demonstrates that loss of these FMRP functions causes marked dysregulation of synaptic information transmission. FMRP-dependent AP broadening is not limited to the hippocampus, but also occurs in cortical pyramidal neurons. Our results thus suggest major translation-independent presynaptic functions of FMRP that may have important implications for understanding FXS neuropathology. PMID:23439122

  18. A potential mode of action for Anakinra in patients with arthrofibrosis following total knee arthroplasty.

    Science.gov (United States)

    Dixon, David; Coates, Jonathon; del Carpio Pons, Alicia; Horabin, Joanna; Walker, Andrew; Abdul, Nicole; Kalson, Nicholas S; Brewster, Nigel T; Weir, David J; Deehan, David J; Mann, Derek A; Borthwick, Lee A

    2015-11-10

    Arthrofibrosis is a fibroproliferative disease characterised by excessive deposition of extracellular matrix components intra-articularly leading to pain and restricted range of movement. Although frequently observed following total knee arthroplasty (TKA) no therapeutic options exist. A pilot study demonstrated that intra-articular injection of Anakinra, an IL-1R antagonist, improved range of movement and pain in patients with arthrofibrosis however the mechanism of action is unknown. We hypothesise that IL-1α/β will drive an inflammatory phenotype in fibroblasts isolated from the knee, therefore identifying a potential mechanism of action for Anakinra in arthrofibrosis following TKA. Fibroblasts isolated from synovial membranes and infra-patellar fat pad of patients undergoing TKA express high levels of IL-1R1. Stimulation with IL-1α/β induced a pro-inflammatory phenotype characterised by increased secretion of GMCSF, IL-6 and IL-8. No significant difference in the inflammatory response was observed between fibroblasts isolated from synovial membrane or infra-patellar fat pad. IL-1α/β treatments induced a pro-inflammatory phenotype in fibroblasts from both synovial membrane and infra-patellar fat pad and therefore Anakinra can likely have an inhibitory effect on fibroblasts present in both tissues in vivo. It is also likely that fibroblast responses in the tissues are controlled by IL-1α/β availability and not their ability to respond to it.

  19. Intracellular recordings of action potentials by an extracellular nanoscale field-effect transistor

    Science.gov (United States)

    Duan, Xiaojie; Gao, Ruixuan; Xie, Ping; Cohen-Karni, Tzahi; Qing, Quan; Choe, Hwan Sung; Tian, Bozhi; Jiang, Xiaocheng; Lieber, Charles M.

    2012-03-01

    The ability to make electrical measurements inside cells has led to many important advances in electrophysiology. The patch clamp technique, in which a glass micropipette filled with electrolyte is inserted into a cell, offers both high signal-to-noise ratio and temporal resolution. Ideally, the micropipette should be as small as possible to increase the spatial resolution and reduce the invasiveness of the measurement, but the overall performance of the technique depends on the impedance of the interface between the micropipette and the cell interior, which limits how small the micropipette can be. Techniques that involve inserting metal or carbon microelectrodes into cells are subject to similar constraints. Field-effect transistors (FETs) can also record electric potentials inside cells, and because their performance does not depend on impedance, they can be made much smaller than micropipettes and microelectrodes. Moreover, FET arrays are better suited for multiplexed measurements. Previously, we have demonstrated FET-based intracellular recording with kinked nanowire structures, but the kink configuration and device design places limits on the probe size and the potential for multiplexing. Here, we report a new approach in which a SiO2 nanotube is synthetically integrated on top of a nanoscale FET. This nanotube penetrates the cell membrane, bringing the cell cytosol into contact with the FET, which is then able to record the intracellular transmembrane potential. Simulations show that the bandwidth of this branched intracellular nanotube FET (BIT-FET) is high enough for it to record fast action potentials even when the nanotube diameter is decreased to 3 nm, a length scale well below that accessible with other methods. Studies of cardiomyocyte cells demonstrate that when phospholipid-modified BIT-FETs are brought close to cells, the nanotubes can spontaneously penetrate the cell membrane to allow the full-amplitude intracellular action potential to be

  20. Distinguishing Selection Bias and Confounding Bias in Comparative Effectiveness Research.

    Science.gov (United States)

    Haneuse, Sebastien

    2016-04-01

    Comparative effectiveness research (CER) aims to provide patients and physicians with evidence-based guidance on treatment decisions. As researchers conduct CER they face myriad challenges. Although inadequate control of confounding is the most-often cited source of potential bias, selection bias that arises when patients are differentially excluded from analyses is a distinct phenomenon with distinct consequences: confounding bias compromises internal validity, whereas selection bias compromises external validity. Despite this distinction, however, the label "treatment-selection bias" is being used in the CER literature to denote the phenomenon of confounding bias. Motivated by an ongoing study of treatment choice for depression on weight change over time, this paper formally distinguishes selection and confounding bias in CER. By formally distinguishing selection and confounding bias, this paper clarifies important scientific, design, and analysis issues relevant to ensuring validity. First is that the 2 types of biases may arise simultaneously in any given study; even if confounding bias is completely controlled, a study may nevertheless suffer from selection bias so that the results are not generalizable to the patient population of interest. Second is that the statistical methods used to mitigate the 2 biases are themselves distinct; methods developed to control one type of bias should not be expected to address the other. Finally, the control of selection and confounding bias will often require distinct covariate information. Consequently, as researchers plan future studies of comparative effectiveness, care must be taken to ensure that all data elements relevant to both confounding and selection bias are collected.

  1. Towards a better understanding of the relationship between belief in the paranormal and statistical bias: The potential role of schizotypy

    Directory of Open Access Journals (Sweden)

    Neil Dagnall

    2016-07-01

    Full Text Available The present paper examined relationships between schizotypy (measured by the Oxford-Liverpool Inventory of Feelings and Experience; O-LIFE scale brief, belief in the paranormal (assessed via the Revised Paranormal Belief Scale; RPBS and proneness to statistical bias (i.e., perception of randomness and susceptibility to conjunction fallacy. Participants were 254 volunteers recruited via convenience sampling. Probabilistic reasoning problems appeared framed within both standard and paranormal contexts. Analysis revealed positive correlations between the Unusual Experience subscale of O-LIFE and paranormal belief measures (RPBS full scale, traditional paranormal beliefs and new age philosophy. Performance on standard problems correlated negatively with Unusual Experience and belief in the paranormal (particularly the traditional paranormal belief dimension of the RPBS. Consideration of specific problem types revealed that perception of randomness associated more strongly with belief in the paranormal than conjunction; both problem types related similarly to Unusual Experience. Structural equation modelling specified that belief in the paranormal mediated the indirect relationship between Unusual Experience and statistical bias. For problems presented in a paranormal context a framing effect occurred. Whilst Unusual Experience correlated positively with conjunction proneness (controlling for perception of randomness, there was no association between Unusual Experience and perception of randomness (controlling for conjunction.

  2. Toward a Better Understanding of the Relationship between Belief in the Paranormal and Statistical Bias: The Potential Role of Schizotypy.

    Science.gov (United States)

    Dagnall, Neil; Denovan, Andrew; Drinkwater, Kenneth; Parker, Andrew; Clough, Peter

    2016-01-01

    The present paper examined relationships between schizotypy (measured by the Oxford-Liverpool Inventory of Feelings and Experience; O-LIFE scale brief), belief in the paranormal (assessed via the Revised Paranormal Belief Scale; RPBS) and proneness to statistical bias (i.e., perception of randomness and susceptibility to conjunction fallacy). Participants were 254 volunteers recruited via convenience sampling. Probabilistic reasoning problems appeared framed within both standard and paranormal contexts. Analysis revealed positive correlations between the Unusual Experience (UnExp) subscale of O-LIFE and paranormal belief measures [RPBS full scale, traditional paranormal beliefs (TPB) and new age philosophy]. Performance on standard problems correlated negatively with UnExp and belief in the paranormal (particularly the TPB dimension of the RPBS). Consideration of specific problem types revealed that perception of randomness associated more strongly with belief in the paranormal than conjunction; both problem types related similarly to UnExp. Structural equation modeling specified that belief in the paranormal mediated the indirect relationship between UnExp and statistical bias. For problems presented in a paranormal context a framing effect occurred. Whilst UnExp correlated positively with conjunction proneness (controlling for perception of randomness), there was no association between UnExp and perception of randomness (controlling for conjunction).

  3. Optimistic bias and Facebook use: self-other discrepancies about potential risks and benefits of Facebook use.

    Science.gov (United States)

    Kim, Sunny Jung; Hancock, Jeffrey T

    2015-04-01

    Despite the accumulating evidence on the positive and negative outcomes of Facebook use, how people perceive themselves to be subject to these outcomes as well as the consequences and mechanisms of these perceptions are underexplored. According to optimistic bias, Facebook users may perceive that bad things are more likely to happen to others than to themselves, while good things are more likely to happen to them than to others. The findings from an online survey among Facebook users indicate that the negative psychological and social outcomes of using Facebook were perceived to be more likely to happen to other Facebook users than to themselves, pFacebook cyberbullying and scams) significantly mediated one's willingness to support Internet regulation, Sobel z=2.49, p=0.01. For positive outcomes of Facebook use, the direction of optimistic bias was reversed, t(235) = -5.52, pFacebook while assessing that other Facebook users are prone to encounter those positive events. This reversal pattern emerged among those with negative attitudes toward, and low involvement with, Facebook. These findings demonstrate important and novel self-other discrepant perceptions concerning the risks and benefits of Facebook use.

  4. A Shab potassium channel contributes to action potential broadening in peptidergic neurons.

    Science.gov (United States)

    Quattrocki, E A; Marshall, J; Kaczmarek, L K

    1994-01-01

    We have cloned the gene for a potassium channel, Aplysia Shab, that is expressed in the bag cell neurons of Aplysia. The voltage dependence and kinetics of the Aplysia Shab current in oocytes match those of IK2, one of the two delayed rectifiers in these neurons. Like IK2, but in contrast with other members of the Shab subfamily, the Aplysia Shab current inactivates within several hundred milliseconds. This inactivation occurs by a process whose properties do not match those previously described for C-type and N-type mechanisms. Neither truncation of the N-terminus nor block by tetraethylammonium alters the time course of inactivation. By incorporating the characteristics of Aplysia Shab into a computational model, we have shown how this current contributes to the normal enhancement of action potentials that occurs in the bag cell neurons at the onset of neuropeptide secretion.

  5. Action potential shape change in an electrically coupled network during propagation: a computer simulation.

    Science.gov (United States)

    Buckingham, Steven D; Spencer, Andrew N

    2008-06-01

    We applied compartmental computer modeling to test a model of spike shape change in the jellyfish, Polyorchis penicillatus, to determine whether adaptive spike shortening can be attributed to the inactivation properties of a potassium channel. We modeled the jellyfish outer nerve-ring as a continuous linear segment, using ion channel and membrane properties derived in earlier studies. The model supported action potentials that shortened as they propagated away from the site of initiation and this was found to be largely independent of potassium channel inactivation. Spike broadening near the site of initiation was found to be due to a depolarization plateau that collapsed as two spikes spread from the point of initiation. The lifetime of this plateau was found to depend critically on the inward current flux and the space constant of the membrane. These data suggest that the spike shape changes may be due not only to potassium channel inactivation, but also to the passive properties of the membrane.

  6. 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

    Purpose. Propofol (2,6-diisopropyl phenol), a widely used systemic anesthetic, is known to potentiate GABA(A) 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 GABA(A) and GABA(C) 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 GABA(C) antagonist), propofol markedly increased the peak amplitude and altered...

  7. Distributed computing for membrane-based modeling of action potential propagation.

    Science.gov (United States)

    Porras, D; Rogers, J M; Smith, W M; Pollard, A E

    2000-08-01

    Action potential propagation simulations with physiologic membrane currents and macroscopic tissue dimensions are computationally expensive. We, therefore, analyzed distributed computing schemes to reduce execution time in workstation clusters by parallelizing solutions with message passing. Four schemes were considered in two-dimensional monodomain simulations with the Beeler-Reuter membrane equations. Parallel speedups measured with each scheme were compared to theoretical speedups, recognizing the relationship between speedup and code portions that executed serially. A data decomposition scheme based on total ionic current provided the best performance. Analysis of communication latencies in that scheme led to a load-balancing algorithm in which measured speedups at 89 +/- 2% and 75 +/- 8% of theoretical speedups were achieved in homogeneous and heterogeneous clusters of workstations. Speedups in this scheme with the Luo-Rudy dynamic membrane equations exceeded 3.0 with eight distributed workstations. Cluster speedups were comparable to those measured during parallel execution on a shared memory machine.

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

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    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

  9. QCD Dirac Spectrum at Finite Chemical Potential: Anomalous Effective Action, Berry Phase and Composite Fermions

    CERN Document Server

    Liu, Yizhuang

    2015-01-01

    We show that the QCD Dirac spectrum at finite chemical potential using a 2-matrix model in the spontaneously broken phase, is amenable to a generic 2-dimensional effective action on a curved eigenvalue manifold. The eigenvalues form a droplet with strong screening and non-linear plasmons. The droplet is threaded by a magnetic vortex which is at the origin of a Berry phase. The adiabatic transport in the droplet maps onto the one in the fractional quantum Hall effect, suggesting that composite fermions at half filling are Dirac particles. We use this observation to argue for two novel anomalous effects in the edge transport of composite fermions, and conversely on a novel contribution to the QCD quark condensate in a rotating frame.

  10. Sequential dissection of multiple ionic currents in single cardiac myocytes under action potential-clamp.

    Science.gov (United States)

    Banyasz, Tamas; Horvath, Balazs; Jian, Zhong; Izu, Leighton T; Chen-Izu, Ye

    2011-03-01

    The cardiac action potential (AP) is shaped by myriad ionic currents. In this study, we develop an innovative AP-clamp Sequential Dissection technique to enable the recording of multiple ionic currents in the single cell under AP-clamp. This new technique presents a significant step beyond the traditional way of recording only one current in any one cell. The ability to measure many currents in a single cell has revealed two hitherto unknown characteristics of the ionic currents in cardiac cells: coordination of currents within a cell and large variation of currents between cells. Hence, the AP-clamp Sequential Dissection method provides a unique and powerful tool for studying individual cell electrophysiology.

  11. Inhomogeneity of action potential waveshape assists frequency entrainment of cardiac pacemaker cells.

    Science.gov (United States)

    Cloherty, S L; Lovell, N H; Celler, B G; Dokos, S

    2001-10-01

    In this paper, we have employed ionic models of sinoatrial node cells to investigate the synchronization of a pair of coupled cardiac pacemaker cells from central and peripheral regions of the sinoatrial node. The free-running cycle length of the cell models was perturbed using two independent techniques and the minimum coupling conductance required to achieve frequency entrainment was used to assess the relative ease with which various cell pairs achieve entrainment. The factors effecting entrainment were further investigated using single-cell models paced with an artificial biphasic coupling current. Our simulation results suggest that dissimilar cell types, those with largely different upstroke velocities entrain more easily, that is, they require less coupling conductance to achieve 1:1 frequency entrainment. We, therefore, propose that regional variation in action-potential waveshape within the sinoatrial node assists frequency synchronization in vivo.

  12. 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.

  13. Optical magnetic detection of single-neuron action potentials using quantum defects in diamond

    CERN Document Server

    Barry, J F; Schloss, J M; Glenn, D R; Song, Y; Lukin, M D; Park, H; Walsworth, R L

    2016-01-01

    A key challenge for neuroscience is noninvasive, label-free sensing of action potential (AP) dynamics in whole organisms with single-neuron resolution. Here, we present a new approach to this problem: using nitrogen-vacancy (NV) quantum defects in diamond to measure the time-dependent magnetic fields produced by single-neuron APs. Our technique has a unique combination of features: (i) it is noninvasive, as the light that probes the NV sensors stays within the biocompatible diamond chip and does not enter the organism, enabling activity monitoring over extended periods; (ii) it is label-free and should be widely applicable to most organisms; (iii) it provides high spatial and temporal resolution, allowing precise measurement of the AP waveforms and conduction velocities of individual neurons; (iv) it directly determines AP propagation direction through the inherent sensitivity of NVs to the associated AP magnetic field vector; (v) it is applicable to neurons located within optically opaque tissue or whole org...

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

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    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.

  15. 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

  16. Action potential broadening induced by lithium may cause a presynaptic enhancement of excitatory synaptic transmission in neonatal rat hippocampus.

    Science.gov (United States)

    Colino, A; García-Seoane, J J; Valentín, A

    1998-07-01

    Lithium enhances excitatory synaptic transmission in CA1 pyramidal cells, but the mechanisms remain unclear. The present study demonstrates that lithium enhances the N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-isoxazole propionic acid (AMPA) receptor-mediated components of the excitatory postsynaptic current (EPSC). Lithium decreased the magnitude of paired-pulse facilitation and presented an inverse correlation between the lithium-induced enhancement of synaptic transmission and initial paired-pulse facilitation, which is consistent with a presynaptic mode of action. The enhancement of synaptic strength is likely to act, at least in part, by increasing the amplitude of the presynaptic Ca2+ transient. One mechanism which could account for this change of the presynaptic Ca2+ transient is an increase in the duration of the action potential. We investigated action potential in hippocampal pyramidal neurons and found that lithium (0.5-6 mM) increased the half-amplitude duration and reduced the rate of repolarization, whereas the rate of depolarization remained similar. To find out whether the lithium synaptic effects might be explained by spike broadening, we investigated the field recording of the excitatory postsynaptic potential (EPSP) in hippocampal slices and found three lines of evidence. First, the prolongation of the presynaptic action potential with 4-aminopyridine and tetraethylammonium blocked or reduced the synaptic effects of lithium. Second, the lithium-induced synaptic enhancement was modulated when presynaptic Ca2+ influx was varied by changing the external Ca2+ concentration. Finally, both effects, the synaptic transmission increment and the action potential broadening, were independent of inositol depletion. These results suggest that lithium enhances synaptic transmission in the hippocampus via a presynaptic site of action: the mechanism underlying the potentiating effect may be attributable to an increased Ca2+ influx consequent

  17. Modulation of hERG potassium channel gating normalizes action potential duration prolonged by dysfunctional KCNQ1 potassium channel

    Science.gov (United States)

    Zhang, Hongkang; Zou, Beiyan; Yu, Haibo; Moretti, Alessandra; Wang, Xiaoying; Yan, Wei; Babcock, Joseph J.; Bellin, Milena; McManus, Owen B.; Tomaselli, Gordon; Nan, Fajun; Laugwitz, Karl-Ludwig; Li, Min

    2012-01-01

    Long QT syndrome (LQTS) is a genetic disease characterized by a prolonged QT interval in an electrocardiogram (ECG), leading to higher risk of sudden cardiac death. Among the 12 identified genes causal to heritable LQTS, ∼90% of affected individuals harbor mutations in either KCNQ1 or human ether-a-go-go related genes (hERG), which encode two repolarizing potassium currents known as IKs and IKr. The ability to quantitatively assess contributions of different current components is therefore important for investigating disease phenotypes and testing effectiveness of pharmacological modulation. Here we report a quantitative analysis by simulating cardiac action potentials of cultured human cardiomyocytes to match the experimental waveforms of both healthy control and LQT syndrome type 1 (LQT1) action potentials. The quantitative evaluation suggests that elevation of IKr by reducing voltage sensitivity of inactivation, not via slowing of deactivation, could more effectively restore normal QT duration if IKs is reduced. Using a unique specific chemical activator for IKr that has a primary effect of causing a right shift of V1/2 for inactivation, we then examined the duration changes of autonomous action potentials from differentiated human cardiomyocytes. Indeed, this activator causes dose-dependent shortening of the action potential durations and is able to normalize action potentials of cells of patients with LQT1. In contrast, an IKr chemical activator of primary effects in slowing channel deactivation was not effective in modulating action potential durations. Our studies provide both the theoretical basis and experimental support for compensatory normalization of action potential duration by a pharmacological agent. PMID:22745159

  18. Regulation and regulatory role of WNT signaling in potentiating FSH action during bovine dominant follicle selection.

    Directory of Open Access Journals (Sweden)

    P S P Gupta

    Full Text Available Follicular development occurs in wave like patterns in monotocous species such as cattle and humans and is regulated by a complex interaction of gonadotropins with local intrafollicular regulatory molecules. To further elucidate potential mechanisms controlling dominant follicle selection, granulosa cell RNA harvested from F1 (largest and F2 (second largest follicles isolated at predeviation (PD and onset of diameter deviation (OD stages of the first follicular wave was subjected to preliminary RNA transcriptome analysis. Expression of numerous WNT system components was observed. Hence experiments were performed to test the hypothesis that WNT signaling modulates FSH action on granulosa cells during follicular waves. Abundance of mRNA for WNT pathway members was evaluated in granulosa cells harvested from follicles at emergence (EM, PD, OD and early dominance (ED stages of the first follicular wave. In F1 follicles, abundance of CTNNB1 and DVL1 mRNAs was higher and AXIN2 mRNA was lower at ED versus EM stages and DVL1 and FZD6 mRNAs were higher and AXIN2 mRNA was lower in F1 versus F2 follicle at the ED stage. Bovine granulosa cells were treated in vitro with increasing doses of the WNT inhibitor IWR-1+/- maximal stimulatory dose of FSH. IWR-1 treatment blocked the FSH-induced increase in granulosa cell numbers and reduced the FSH-induced increase in estradiol. Granulosa cells were also cultured in the presence or absence of FSH +/- IWR-1 and hormonal regulation of mRNA for WNT pathway members and known FSH targets determined. FSH treatment increased CYP19A1, CCND2, CTNNB1, AXIN2 and FZD6 mRNAs and the stimulatory effect on CYP19A1 mRNA was reduced by IWR-1. In contrast, FSH reduced CARTPT mRNA and IWR-1 partially reversed the inhibitory effect of FSH. Results support temporal and hormonal regulation and a potential role for WNT signaling in potentiating FSH action during dominant follicle selection.

  19. 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.

  20. 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.

  1. 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.

  2. Zinc-related actions of sublethal levels of benzalkonium chloride: Potentiation of benzalkonium cytotoxicity by zinc.

    Science.gov (United States)

    Mitani, Tsuyoshi; Elmarhomy, Ahmed Ibrahim Elhossany; Dulamjav, Luvsandorj; Anu, Enkhtumur; Saitoh, Shohei; Ishida, Shiro; Oyama, Yasuo

    2017-04-25

    Benzalkonium chloride (BZK) is a common preservative used in pharmaceutical and personal care products. ZnCl2 was recently reported to significantly potentiate the cytotoxicity of some biocidal compounds. In the present study, therefore, we compared the cytotoxic potency of BZK and then further studied the Zn(2+)-related actions of the most cytotoxic agent among BZK, using flow cytometric techniques with appropriate fluorescent probes in rat thymocytes. Cytotoxicity of benzylcetyldimethylammonium (BZK-C16) was more potent that those of benzyldodecyldimethylammonium and benzyldimethyltetradecylammonium. ZnCl2 (1-10 μM) significantly potentiated the cytotoxicity of BZK-C16 at a sublethal concentration (1 μM). The co-treatment of cells with 3 μM ZnCl2 and 1 μM BZK-C16 increased the population of both living cells with phosphatidylserine exposed on membrane surfaces and dead cells. BZK-C16 at 0.3-1.0 μM elevated intracellular Zn(2+) levels by increasing Zn(2+) influx, and augmented the cytotoxicity of 100 μM H2O2. Zn(2+) is concluded to facilitate the toxicity of BZK. We suggest that the toxicity of BZK is determined after taking extracellular (plasma) and/or environmental Zn(2+) levels into account.

  3. Glutamate induces series of action potentials and a decrease in circumnutation rate in Helianthus annuus.

    Science.gov (United States)

    Stolarz, Maria; Król, Elzbieta; Dziubińska, Halina; Kurenda, Andrzej

    2010-03-01

    Reports concerning the function of glutamate (Glu) in the electrical and movement phenomena in plants are scarce. Using the method of extracellular measurement, we recorded electrical potential changes in the stem of 3-week-old Helianthus annuus L. plants after injection of Glu solution. Simultaneously, circumnutation movements of the stem were measured with the use of time-lapse images. Injection of Glu solution at millimolar (200, 50, 5 mM) concentrations in the basal part of the stem evoked a series of action potentials (APs). The APs appeared in the site of injection and in different parts of the stem and were propagated acropetally and/or basipetally along the stem. Glu injection also resulted in a transient, approximately 5-h-long decrease in the stem circumnutation rate. The APs initiated and propagating in the sunflower stem after Glu injection testify the existence of a Glu perception system in vascular plants and suggest its involvement in electrical, long-distance signaling. Our experiments also demonstrated that Glu is a factor affecting circumnutation movements.

  4. Calcium Transients Closely Reflect Prolonged Action Potentials in iPSC Models of Inherited Cardiac Arrhythmia

    Directory of Open Access Journals (Sweden)

    C. Ian Spencer

    2014-08-01

    Full Text Available Long-QT syndrome mutations can cause syncope and sudden death by prolonging the cardiac action potential (AP. Ion channels affected by mutations are various, and the influences of cellular calcium cycling on LQTS cardiac events are unknown. To better understand LQTS arrhythmias, we performed current-clamp and intracellular calcium ([Ca2+]i measurements on cardiomyocytes differentiated from patient-derived induced pluripotent stem cells (iPS-CM. In myocytes carrying an LQT2 mutation (HERG-A422T, APs and [Ca2+]i transients were prolonged in parallel. APs were abbreviated by nifedipine exposure and further lengthened upon releasing intracellularly stored Ca2+. Validating this model, control iPS-CM treated with HERG-blocking drugs recapitulated the LQT2 phenotype. In LQT3 iPS-CM, expressing NaV1.5-N406K, APs and [Ca2+]i transients were markedly prolonged. AP prolongation was sensitive to tetrodotoxin and to inhibiting Na+-Ca2+ exchange. These results suggest that LQTS mutations act partly on cytosolic Ca2+ cycling, potentially providing a basis for functionally targeted interventions regardless of the specific mutation site.

  5. Backpropagating Action Potentials Enable Detection of Extrasynaptic Glutamate by NMDA Receptors

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    Yu-Wei Wu

    2012-05-01

    Full Text Available Synaptic NMDA receptors (NMDARs are crucial for neural coding and plasticity. However, little is known about the adaptive function of extrasynaptic NMDARs occurring mainly on dendritic shafts. Here, we find that in CA1 pyramidal neurons, backpropagating action potentials (bAPs recruit shaft NMDARs exposed to ambient glutamate. In contrast, spine NMDARs are “protected,” under baseline conditions, from such glutamate influences by perisynaptic transporters: we detect bAP-evoked Ca2+ entry through these receptors upon local synaptic or photolytic glutamate release. During theta-burst firing, NMDAR-dependent Ca2+ entry either downregulates or upregulates an h-channel conductance (Gh of the cell depending on whether synaptic glutamate release is intact or blocked. Thus, the balance between activation of synaptic and extrasynaptic NMDARs can determine the sign of Gh plasticity. Gh plasticity in turn regulates dendritic input probed by local glutamate uncaging. These results uncover a metaplasticity mechanism potentially important for neural coding and memory formation.

  6. Potential involvement of serotonergic signaling in ketamine's antidepressant actions: A critical review.

    Science.gov (United States)

    du Jardin, Kristian Gaarn; Müller, Heidi Kaastrup; Elfving, Betina; Dale, Elena; Wegener, Gregers; Sanchez, Connie

    2016-11-03

    A single i.v. infusion of ketamine, classified as an N-methyl-d-aspartate (NMDA) receptor antagonist, may alleviate depressive symptoms within hours of administration in treatment resistant depressed patients, and the antidepressant effect may last for several weeks. These unique therapeutic properties have prompted researchers to explore the mechanisms mediating the antidepressant effects of ketamine, but despite many efforts, no consensus on its antidepressant mechanism of action has been reached. Recent preclinical reports have associated the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) with the antidepressant-like action of ketamine. Here, we review the current evidence for a serotonergic role in ketamine's antidepressant effects. The pharmacological profile of ketamine may include equipotent activity on several non-NMDA targets, and the current hypotheses for the mechanisms responsible for ketamine's antidepressant activity do not appear to preclude the possibility that non-glutamate neurotransmitters are involved in the antidepressant effects. At multiple levels, the serotonergic and glutamatergic systems interact, and such crosstalk could support the notion that changes in serotonergic neurotransmission may impact ketamine's antidepressant potential. In line with these prospects, ketamine may increase 5-HT levels in the prefrontal cortex of rats, plausibly via hippocampal NMDA receptor inhibition and activation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors. In addition, a number of preclinical studies suggest that the antidepressant-like effects of ketamine may depend on endogenous activation of 5-HT receptors. Recent imaging and behavioral data predominantly support a role for 5-HT1A or 5-HT1B receptors, but the full range of 5-HT receptors has currently not been systematically investigated in this context. Furthermore, the nature of any 5-HT dependent mechanism in ketamine's antidepressant effect is currently not

  7. Different mechanisms underlying the repolarization of narrow and wide action potentials in pyramidal cells and interneurons of cat motor cortex.

    Science.gov (United States)

    Chen, W; Zhang, J J; Hu, G Y; Wu, C P

    1996-07-01

    Two different types of action potentials were observed among the pyramidal cells and interneurons in cat motor cortex: the narrow action potentials and the wide action potentials. These two types of action potentials had similar rising phases (528.8 +/- 77.0 vs 553.1 +/- 71.8 mV/ms for the maximal rising rate), but differed in spike duration (0.44 +/- 0.09 vs 1.40 +/- 0.39 ms) and amplitude (57.31 +/- 8.22 vs 72.52 +/- 8.31 mV), implying that the ionic currents contributing to repolarization of these action potentials are different. Here we address this issue by pharmacological manipulation and using voltage-clamp technique in slices of cat motor cortex. Raising extracellular K+ concentration (from 3 mM to 10 mM), applying a low dose of 4-aminopyridine (2-200 microM) or administering a low concentration of tetraethylammonium (0.2-1.0 mM) each not only broadened the narrow action potentials, but also increased their amplitudes. In contrast, high K+ medium or low dose of tetraethylammonium only broadened the wide action potentials, leaving their amplitudes unaffected, and 4-aminopyridine had only a slight broadening effect on the wide spikes. These results implied that K+ currents were involved in the repolarization of both types of action potentials, and that the K+ currents in the narrow action potentials seemed to activate much earlier than those in the wide spikes. This early activated K+ current may counteract the rapid sodium current, yielding the extremely brief duration and small amplitude of the narrow spikes. The sensitivity of the narrow spikes to 4-aminopyridine may not be mainly attributed to blockade of the classical A current (IA), because depolarizing the membrane potential to inactivate IA did not reproduce the effects of 4-aminopyridine. Blockade of Ca2+ influx slowed the last two-thirds repolarization of the wide action potentials. On the contrary, the narrow action potentials were not affected by Ca(2+)-current blockers, but if they were first

  8. 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

  9. Surface electrocardiogram and action potential in mice lacking urea transporter UT-B

    Institute of Scientific and Technical Information of China (English)

    MENG Yan; ZHAO ChunYan; ZHANG XueXin; ZHAO HuaShan; GUO LiRong; Lü Bin; ZHAO XueJian; YANG BaoXue

    2009-01-01

    UT-B is a urea transporter protein expressed in the kidney and in many non-renal tissues including erythrocytes, brain, heart, bladder and the testis. The objective of this study was to determine the phenotype of UT-B deletion in the heart. UT-B expression in the heart was studied in wild-type mice vs UT-B null mice by utilizing RT-PCR and Western blot. A surface electrocardiogram (ECG) recording (lead Ⅱ) was measured in wild-type mice and UT-B null mice at the ages of 6, 16 and 52 weeks. For the action potential recording, the ventricular myocytes of 16 w mice were isolated and recorded by float-ing microelectrode method. The sodium current was recorded by the patch clamp technique. RT-PCR and Western blot showed the UT-B expression in the heart of wild-type mice. No UT-B transcript and protein was found in UT-B null mice. The ECG recording showed that the P-R interval was significantly prolonged in UT-B null mice ((43.5±4.2), (45.5±6.9) and (43.8±7.6) ms at ages of 6, 16 and 52 weeks) vs wild-type mice ((38.6±2.9), (38.7±5.6) and (38.2±7.3) ms, P<0.05). The atrial ventricular heart block type Ⅱ and Ⅲ only appeared in the aging UT-B null mice (52 w old). The amplitude of action potential and Vmax decreased significantly in UT-B null mice ((92.17±10.56) and (101.89±9.54) mV/s) vs those in wild-type mice (vs (110.51±10.38) and (109.53±10.64) mV/s, P<0.05). The action potential duration at 50% and 90% (APD50 and APD90) was significantly prolonged in UT-B null mice ((123.83±11.17) and (195.43±16.41) ms) vs that in wild-type mice ((108.27±10.85) and (171.00±15.53) ms, P<0.05). The maximal sodium current decreased significantly in UT-B null mice (-8.80±0.92) nA vs that in wild-type mice ((-5.98±1.07) nA, P<0.05). These results provide the first evidence that UT-B deletion causes progressive heart block in mice.

  10. Surface electrocardiogram and action potential in mice lacking urea transporter UT-B

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    UT-B is a urea transporter protein expressed in the kidney and in many non-renal tissues including erythrocytes, brain, heart, bladder and the testis. The objective of this study was to determine the phenotype of UT-B deletion in the heart. UT-B expression in the heart was studied in wild-type mice vs UT-B null mice by utilizing RT-PCR and Western blot. A surface electrocardiogram (ECG) recording (lead II) was measured in wild-type mice and UT-B null mice at the ages of 6, 16 and 52 weeks. For the action potential recording, the ventricular myocytes of 16 w mice were isolated and recorded by floating microelectrode method. The sodium current was recorded by the patch clamp technique. RT-PCR and Western blot showed the UT-B expression in the heart of wild-type mice. No UT-B transcript and protein was found in UT-B null mice. The ECG recording showed that the P-R interval was significantly prolonged in UT-B null mice ((43.5 ± 4.2), (45.5 ± 6.9) and (43.8 ± 7.6) ms at ages of 6, 16 and 52 weeks) vs wild-type mice ((38.6 ± 2.9), (38.7 ± 5.6) and (38.2 ± 7.3) ms, P<0.05). The atrial ventricular heart block type II and III only appeared in the aging UT-B null mice (52 w old). The amplitude of action potential and Vmax decreased significantly in UT-B null mice ((92.17 ± 10.56) and (101.89 ± 9.54) mV/s) vs those in wild-type mice (vs (110.51 ± 10.38) and (109.53 ± 10.64) mV/s, P<0.05). The action potential duration at 50% and 90% (APD50 and APD90) was significantly prolonged in UT-B null mice ((123.83 ± 11.17) and (195.43 ± 16.41) ms) vs that in wild-type mice ((108.27 ± 10.85) and (171.00 ± 15.53) ms, P<0.05). The maximal sodium current decreased significantly in UT-B null mice (-8.80 ± 0.92) nA vs that in wild-type mice ((-5.98 ± 1.07) nA, P<0.05). These results provide the first evidence that UT-B deletion causes progressive heart block in mice.

  11. An experimental study on the physical properties of the cupula. Effect of cupular sectioning on the ampullary nerve action potential.

    Science.gov (United States)

    Suzuki, M; Harada, Y; Kishimoto, A

    1985-01-01

    The frog posterior semicircular canal (PSC) was isolated and a part of the ampullary wall was cut to allow removal of the cupula from the crista. The cupula was replaced on the crista and the PSC ampullary action potential was recorded. The cupula was again removed and was sectioned in half, either in the plane vertical to the crista (vertical sectioning), or in the plane parallel to the crista (horizontal sectioning). The sectioned half of the cupula was then replaced on the crista. The action potentials after replacement of the vertical or horizontal segments of the cupula were compared to those achieved when the entire cupula was replaced. After vertical sectioning, the action potentials were significantly reduced; they were 50.3% of the completely replaced cupula when a small stimulus was used and 79.1% when a large stimulus was used. A reduced attachment surface between the cupular base and the crista is possibly responsible for the decreased action potential in the vertically sectioned specimen. After horizontal sectioning, the action potentials were 64.5% for the small stimulus and 108.2% for the large stimulus. These results indicate that elicited responses are related to the height of the cupula and the deflection angle. This further suggests that the movement of the cupula is represented by that of the elastic system.

  12. CLINICAL AND EXPERIMENTAL STUDIES OF LARGE AMPLITUDE ACTION POTENTIAL OF THE SUFFERED FACIAL MUSCLES IN INTRATEMPORAL FACIAL NERVE PARALYSIS

    Institute of Scientific and Technical Information of China (English)

    任重; 惠莲

    1999-01-01

    Objctive. To testify the phenomenon that large amplitude action potential appears at the early stage oil facial paralysis, and to search for the mechanism through clinical and experimental studies. Patients(aninmls) and methods. The action potentials of the orbicular ocular and oral museles were recorded in 34 normal persons by electromyogram instrtiments. The normal range of amplitude percentage was found out according to the normal distribution, One hundred patients with facial paralysis were also studied. The action potentials of facial muscles were recorded ia 17 guinea pigs before and after the facial nerve was comp~ and the facial nerve was examined under electromicroscope before and after the compression.Results. The amplitude percentage of the suffered side to the healthy side was more than 153 percent in 6 of the 100 patients. Large amplitude action potential occured in 35 per cent guinea pigs which were performed the experiment of facial nerve compression. Electromicroscopic examination revealed separation of the lammae of the facial nerve's myelin sheath in the guinea pigs which exhibited large amplitude action potential Conclusion. The facial nerve exhibited a temporary over-excitability at the early stage of facial nerve injury in scane patients and guinea pigs. If the injury was limited in the myelin sheath, the prognods was relatively good.

  13. CLINICAL AND EXPERIMENTAL STUDIES OF LARGE AMPLITUDE ACTION POTENTIAL OF THE SUFFERED FACIAL MUSCLES IN INTRATEMPORAL FACIAL NERVE PARALYSIS

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Ojective. To testify the phenomenon that large amplitude action potential appears at the early stage of facial paralysis, and to search for the mechanism through clinical and experimental studies. Patients(animals) and methods. The action potentials of the orbicular ocular and oral muscles were recorded in 34 normal persons by electromyogram instruments. The normal range of amplitude percentage was found out according to he normal distribution. One hundred patients with facial paralysis were also studied. The action potentials of facial muscles were recorded in 17 guinea pigs before and after the facial nerve was compressed and the facial nerve was examined under electromicroscope before and after the compression.Results. The amplitude percentage of the suffered ide to the healthy side was more than 153 percent in 6 of the 100 patients. Lare amplitude action potential ocured in 35 per cent guinea pigs which were performed the experiment of facial nrve compression. Electromicroscopic examination revealed separation of the lammae of the facial nerve's myelin sheath in the guinea pigs which exhibited large amplitude action potential.Conclusion. The facial nerve exhibited a temporary over-exciability at the early stage of facial nerve injury in some patients and guinea pigs. If the injury waslimited in the myelin sheath, te prognosis was relatively good.

  14. Surface electrocardiogram and action potential in mice lacking urea transporter UT-B.

    Science.gov (United States)

    Meng, Yan; Zhao, Chunyan; Zhang, Xuexin; Zhao, Huashan; Guo, Lirong; Lü, Bin; Zhao, Xuejian; Yang, Baoxue

    2009-05-01

    UT-B is a urea transporter protein expressed in the kidney and in many non-renal tissues including erythrocytes, brain, heart, bladder and the testis. The objective of this study was to determine the phenotype of UT-B deletion in the heart. UT-B expression in the heart was studied in wild-type mice vs UT-B null mice by utilizing RT-PCR and Western blot. A surface electrocardiogram (ECG) recording (lead II) was measured in wild-type mice and UT-B null mice at the ages of 6, 16 and 52 weeks. For the action potential recording, the ventricular myocytes of 16 w mice were isolated and recorded by floating microelectrode method. The sodium current was recorded by the patch clamp technique. RT-PCR and Western blot showed the UT-B expression in the heart of wild-type mice. No UT-B transcript and protein was found in UT-B null mice. The ECG recording showed that the P-R interval was significantly prolonged in UT-B null mice ((43.5 +/- 4.2), (45.5 +/- 6.9) and (43.8 +/- 7.6) ms at ages of 6, 16 and 52 weeks) vs wild-type mice ((38.6 +/- 2.9), (38.7 +/- 5.6) and (38.2 +/- 7.3) ms, PUT-B null mice (52 w old). The amplitude of action potential and V (max) decreased significantly in UT-B null mice ((92.17 +/- 10.56) and (101.89 +/- 9.54) mV/s) vs those in wild-type mice (vs (110.51 +/- 10.38) and (109.53 +/- 10.64) mV/s, PUT-B null mice ((123.83 +/- 11.17) and (195.43 +/- 16.41) ms) vs that in wild-type mice ((108.27 +/- 10.85) and (171.00 +/- 15.53) ms, PUT-B null mice (-8.80 +/- 0.92) nA vs that in wild-type mice ((-5.98 +/- 1.07) nA, PUT-B deletion causes progressive heart block in mice.

  15. Action potential repolarization and a fast after-hyperpolarization in rat hippocampal pyramidal cells.

    Science.gov (United States)

    Storm, J F

    1987-04-01

    1. The repolarization of the action potential, and a fast after-hyperpolarization (a.h.p.) were studied in CA1 pyramidal cells (n = 76) in rat hippocampal slices (28-37 degrees C). Single spikes were elicited by brief (1-3 ms) current pulses, at membrane potentials close to rest (-60 to -70 mV). 2. Each action potential was followed by four after-potentials: (a) the fast a.h.p., lasting 2-5 ms; (b) an after-depolarization; (c) a medium a.h.p., (50-100 ms); and (d) a slow a.h.p. (1-2 s). Both the fast a.h.p. and the slow a.h.p. (but not the medium a.h.p.) were inhibited by Ca2+-free medium or Ca2+-channel blockers (Co2+, Mn2+ or Cd2+); but tetraethylammonium (TEA; 0.5-2 nM) blocked only the fast a.h.p., and noradrenaline (2-5 microM) only the slow a.h.p. This suggests that two Ca2+-activated K+ currents were involved: a fast, TEA-sensitive one (IC) underlying the fast a.h.p., and a slow noradrenaline-sensitive one (IAHP) underlying the slow a.h.p. 3. Like the fast a.h.p., spike repolarization seems to depend on a Ca2+-dependent K+ current of the fast, TEA-sensitive kind (IC). The repolarization was slowed by Ca2+-free medium, Co2+, Mn2+, Cd2+, or TEA, but not by noradrenaline. Charybdotoxin (CTX; 30 nM), a scorpion toxin which blocks the large-conductance Ca2+-activated K+ channel in muscle, had a similar effect to TEA. The effects of TEA and Cd2+ (or Mn2+) showed mutual occlusion. Raising the external K+ concentration reduced the fast a.h.p. and slowed the spike repolarization, whereas Cl- loading of the cell was ineffective. 4. The transient K+ current, IA, seems also to contribute to spike repolarization, because: (a) 4-aminopyridine (4-AP; 0.1 mM), which blocks IA, slowed the spike repolarization; (b) depolarizing pre-pulses, which inactivate IA, had a similar effect; (c) hyperpolarizing pre-pulses speeded up the spike repolarization; (d) the effects of 4-AP and pre-pulses persisted during Ca2+ blockade (like IA); and (e) depolarizing pre-pulses reduced the

  16. 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.

  17. 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.

  18. Kv3.1 uses a timely resurgent K(+) current to secure action potential repolarization.

    Science.gov (United States)

    Labro, Alain J; Priest, Michael F; Lacroix, Jérôme J; Snyders, Dirk J; Bezanilla, Francisco

    2015-12-17

    High-frequency action potential (AP) transmission is essential for rapid information processing in the central nervous system. Voltage-dependent Kv3 channels play an important role in this process thanks to their high activation threshold and fast closure kinetics, which reduce the neuron's refractory period. However, premature Kv3 channel closure leads to incomplete membrane repolarization, preventing sustainable AP propagation. Here, we demonstrate that Kv3.1b channels solve this problem by producing resurgent K(+) currents during repolarization, thus ensuring enough repolarizing power to terminate each AP. Unlike previously described resurgent Na(+) and K(+) currents, Kv3.1b's resurgent current does not originate from recovery of channel block or inactivation but results from a unique combination of steep voltage-dependent gating kinetics and ultra-fast voltage-sensor relaxation. These distinct properties are readily transferrable onto an orthologue Kv channel by transplanting the voltage-sensor's S3-S4 loop, providing molecular insights into the mechanism by which Kv3 channels contribute to high-frequency AP transmission.

  19. Latencies in action potential stimulation in a two-dimensional bidomain: A numerical simulation

    Science.gov (United States)

    Barach, John Paul

    1991-05-01

    A numerical simulation is performed in which a uniform planar slab of idealized cardiac tissue is stimulated at the center. The cardiac slab is modeled as an anisotropic bidomain; within each domain current flow is determined by a forced diffusion equation in which the transmembrane current connecting the domains provides the forcing term. An action potential (AP) propagates outward after a time latency dependent upon the stimulus size and the physiological variables. Its isochrones are elliptical with an asymmetry that is a small fraction of the imposed asymmetry in resistivity. External voltages resemble the first derivative of those in the internal domain and tests with continuing stimuli exhibit a relaxation time of about 3 ms and space constants that agree with other work. The AP latency increases very strongly near threshold stimulus and decreases as the log (stimulus) for large stimuli in the ``virtual cathode'' range. Latencies in the longitudinal, transverse, and diagonal directions are found to be the same over a wide range of stimulus size and type.

  20. Diaphragm compound muscle action potential measured with magnetic stimulation and chest wall surface electrodes.

    Science.gov (United States)

    Luo, Y M; Mustfa, N; Lyall, R A; Man, W D C; Glérant, J C; Polkey, M I; Moxham, J

    2002-06-01

    To seek a method to reliably measure phrenic nerve conduction time (PNCT) with magnetic stimulation we investigated two stimulus sites, placing the magnetic coil at the cricoid cartilage (high position) or close to the clavicle (low position). We also compared compound muscle action potential (CMAP) recorded from three different sites: in the sixth to eighth intercostal spaces in the anterior axillary line (Ant-a); in the 8th intercostal space close to the midclavicular line; and with one electrode at the lower sternum and the other at the costal margin. Fourteen normal subjects were studied. The PNCT measured by magnetic stimulation in the high position recorded from (Ant-a) was 7.6+/-0.6 on the left side and 8.4+/-0.7 on the right. The PNCT recorded from all three sites become much shorter when the magnetic coil was moved from the high to the low position. Our results show that PNCT can be accurately measured with magnetic stimulation when care is taken to avoid coactivation of the brachial plexus.

  1. Modulation of action potential trains in rabbit saphenous nerve unmyelinated fibers.

    Science.gov (United States)

    Zhu, Zhi-Ru; Liu, Yi-Hui; Ji, Wei-Gang; Duan, Jian-Hong; Hu, San-Jue

    2013-01-01

    Usually, the main axon is assumed to faithfully conduct action potentials (APs). Recent data have indicated that neural processing can occur along the axonal path. However, the patterns and mechanisms of temporal coding are not clear. In the present study, single fiber recording was used to analyze activity-dependent modulation of AP trains in the main axons of C fibers in the rabbit saphenous nerve. Trains of 5 superthreshold electrical pulses at interstimulus intervals of 20 or 50 ms were applied to the nerve trunk for 200 s. The interspike intervals (ISIs) for these trains were compared to the input interstimulus intervals. Three basic types of C fibers were observed in response to repeated stimuli: first, the ISI between the first and second AP (ISI1-2) of type 1 was longer than the interstimulus interval; second, the ISI1-2 of type 2 showed wavelike fluctuations around the interstimulus interval, and third, the ISI1-2 of type 3 exhibited shorter intervals for a long period. Furthermore, both 4-aminopyridine-sensitive potassium and hyperpolarization-activated cation currents were involved in the modulation of ISI1-2 of train pulses. These data provide new evidence that multiple modes of neural conduction can occur along the main axons of C fibers.

  2. 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.

  3. 'Action potential-like' ST elevation following pseudo-Wellens' electrocardiogram.

    Science.gov (United States)

    Oksuz, Fatih; Sensoy, Baris; Sen, Fatih; Celik, Ethem; Ozeke, Ozcan; Maden, Orhan

    2015-01-01

    Coronary artery vasospasm is an important cause of chest pain syndromes that can lead to myocardial infarction, ventricular arrhythmias, and sudden death. In 1959, Prinzmetal et al described a syndrome of nonexertional chest pain with ST-segment elevation on electrocardiography. Persistent angina is challenging, and repeated coronary angioplasty may be required in this syndrome. Calcium antagonists are extremely effective in treating and preventing coronary spasm, and may provide long-lasting relief for the patient. Whereas the Wellens' syndrome is characterized by symmetrically inverted T-waves with preserved R waves in the precordial leads suggestive of impending myocardial infarction due to a critical proximal left anterior descending stenosis, the pseudo-Wellens' syndrome caused by coronary artery spasm has also rarely been reported in literature. We present a pseudo-Wellens syndrome as a cause of vasospastic angina, and a diffuse ST segment elavation on electrocardiogram resembling the Greek letter lambda, called also 'action potential-like' ECG in a patient with vasospastic-type Printzmetal angina.

  4. 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.

  5. Wavelet transform for real-time detection of action potentials in neural signals.

    Science.gov (United States)

    Quotb, Adam; Bornat, Yannick; Renaud, Sylvie

    2011-01-01

    We present a study on wavelet detection methods of neuronal action potentials (APs). Our final goal is to implement the selected algorithms on custom integrated electronics for on-line processing of neural signals; therefore we take real-time computing as a hard specification and silicon area as a price to pay. Using simulated neural signals including APs, we characterize an efficient wavelet method for AP extraction by evaluating its detection rate and its implementation cost. We compare software implementation for three methods: adaptive threshold, discrete wavelet transform (DWT), and stationary wavelet transform (SWT). We evaluate detection rate and implementation cost for detection functions dynamically comparing a signal with an adaptive threshold proportional to its SD, where the signal is the raw neural signal, respectively: (i) non-processed; (ii) processed by a DWT; (iii) processed by a SWT. We also use different mother wavelets and test different data formats to set an optimal compromise between accuracy and silicon cost. Detection accuracy is evaluated together with false negative and false positive detections. Simulation results show that for on-line AP detection implemented on a configurable digital integrated circuit, APs underneath the noise level can be detected using SWT with a well-selected mother wavelet, combined to an adaptive threshold.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. 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.

  8. A new three-variable mathematical model of action potential propagation in cardiac tissue.

    Science.gov (United States)

    Fenton, Flavio; Karma, Alain

    1996-03-01

    Modeling the electrical activity of the heart, and the complex signaling patterns which underly dangerous arrhythmias such as tachycardia and fibrillation, requires a quantitative model of action potential (AP) propagation. At present, there exist detailed ionic models of the Hodgkin-Huxley form that accurately reproduce dynamical features of the AP at a single cell level (e.g. Luo-Rudy, 1994). However, such models are not computationally tractable to study propagation in two and three-dimensional tissues of many resistively coupled cells. At the other extreme, there exists generic models of excitable media, such as the well-known FitzHugh-Nagumo model, which are only qualitative and do not reproduce essential dynamical features of cardiac AP. A new three-variable model is introduced which bridges the gap between these two types of models. It reproduces quantitatively important `mesoscopic' dynamical properties which are specific to cardiac AP, namely restitution and dispersion. At the same time, it remains computationally tractable and makes it possible to study the effect of these properties on the initiation, dynamics, and stability of complex reentrant excitations in two and three dimensions. Preliminary numerical results of the effect of restitution and dispersion on two-dimensional reentry (i.e. spiral waves) are presented.

  9. 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.

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

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    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.

  11. Direction-selective circuitry in rat retina develops independently of GABAergic, cholinergic and action potential activity.

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    Le Sun

    Full Text Available The ON-OFF direction selective ganglion cells (DSGCs in the mammalian retina code image motion by responding much more strongly to movement in one direction. They do so by receiving inhibitory inputs selectively from a particular sector of processes of the overlapping starburst amacrine cells, a type of retinal interneuron. The mechanisms of establishment and regulation of this selective connection are unknown. Here, we report that in the rat retina, the morphology, physiology of the ON-OFF DSGCs and the circuitry for coding motion directions develop normally with pharmacological blockade of GABAergic, cholinergic activity and/or action potentials for over two weeks from birth. With recent results demonstrating light independent formation of the retinal DS circuitry, our results strongly suggest the formation of the circuitry, i.e., the connections between the second and third order neurons in the visual system, can be genetically programmed, although emergence of direction selectivity in the visual cortex appears to require visual experience.

  12. 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.

  13. 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.

  14. A regenerative microchannel device for recording multiple single-unit action potentials in awake, ambulatory animals.

    Science.gov (United States)

    Srinivasan, Akhil; Tipton, John; Tahilramani, Mayank; Kharbouch, Adel; Gaupp, Eric; Song, Chao; Venkataraman, Poornima; Falcone, Jessica; Lacour, Stéphanie P; Stanley, Garrett B; English, Arthur W; Bellamkonda, Ravi V

    2016-02-01

    Despite significant advances in robotics, commercially advanced prosthetics provide only a small fraction of the functionality of the amputated limb that they are meant to replace. Peripheral nerve interfacing could provide a rich controlling link between the body and these advanced prosthetics in order to increase their overall utility. Here, we report on the development of a fully integrated regenerative microchannel interface with 30 microelectrodes and signal extraction capabilities enabling evaluation in an awake and ambulatory rat animal model. In vitro functional testing validated the capability of the microelectrodes to record neural signals similar in size and nature to those that occur in vivo. In vitro dorsal root ganglia cultures revealed striking cytocompatibility of the microchannel interface. Finally, in vivo, the microchannel interface was successfully used to record a multitude of single-unit action potentials through 63% of the integrated microelectrodes at the early time point of 3 weeks. This marks a significant advance in microchannel interfacing, demonstrating the capability of microchannels to be used for peripheral nerve interfacing.

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

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    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.

  16. Potential action of androstenedione on the proliferation and apoptosis of stromal endometrial cells

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    Anido Mabel

    2004-12-01

    Full Text Available Abstract Background Hyperandrogenic conditions have been associated with a high prevalence of endometrial pathologies related to cell survival. However, the action of androgens on proliferation and apoptosis in endometrial cells is poorly understood. Therefore, the aim of the present study was to evaluate the effect of androstenedione on cell proliferation, cell death and expression of estrogen receptor (ER isoforms and proteins related to apoptosis in endometrial cells using two in vitro experimental approaches. Methods The endometrial tissue was obtained from 20 eumenorrheic women [28.7 (25 – 35 years] during the early secretory phase. We analyzed cell proliferation (immunohistochemistry of Ki-67 and spectrophotometric assay; apoptosis (DNA fragmentation (TUNEL and Annexin V-FITC binding; ER-alpha, ER-beta bcl-2 and bax mRNA abundance (RT-PCR in explants and isolated endometrial epithelial (EEC and stromal cells (ESC incubated with androstenedione 1 micro mol/l (A4 or A4 plus hydroxyflutamide 10 micro mol/l (F for 24 h. Results In explants, A4 induced an increase of cell proliferation and a decrease on apoptosis in the stromal compartment (p Conclusions These results indicate that androstenedione may modulate cell survival, expression of ER-beta and proteins related to apoptosis, suggesting a potential mechanism that associates the effect of hyperandrogenemia on the endometrial tissue.

  17. Action potential generation in an anatomically constrained model of medial superior olive axons.

    Science.gov (United States)

    Lehnert, Simon; Ford, Marc C; Alexandrova, Olga; Hellmundt, Franziska; Felmy, Felix; Grothe, Benedikt; Leibold, Christian

    2014-04-09

    Neurons in the medial superior olive (MSO) encode interaural time differences (ITDs) with sustained firing rates of >100 Hz. They are able to generate such high firing rates for several hundred milliseconds despite their extremely low-input resistances of only few megaohms and high synaptic conductances in vivo. The biophysical mechanisms by which these leaky neurons maintain their excitability are not understood. Since action potentials (APs) are usually assumed to be generated in the axon initial segment (AIS), we analyzed anatomical data of proximal MSO axons in Mongolian gerbils and found that the axon diameter is <1 μm and the internode length is ∼100 μm. Using a morphologically constrained computational model of the MSO axon, we show that these thin axons facilitate the excitability of the AIS. However, for ongoing high rates of synaptic inputs the model generates a substantial fraction of APs in its nodes of Ranvier. These distally initiated APs are mediated by a spatial gradient of sodium channel inactivation and a strong somatic current sink. The model also predicts that distal AP initiation increases the dynamic range of the rate code for ITDs.

  18. Dispersion of compound muscle action potential in hereditary neuropathies and chronic inflammatory demyelinating polyneuropathy.

    Science.gov (United States)

    Stanton, Michael; Pannoni, Valerie; Lewis, Richard A; Logigian, Eric L; Naguib, Demian; Shy, Michael E; Cleland, James; Herrmann, David N

    2006-10-01

    Distal compound muscle action potential (DCMAP) dispersion, defined as a DCMAP duration > or = 9 ms, and proximal-distal (P-D) CMAP dispersion are considered useful in the electrodiagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP). Distal and P-D CMAP dispersion have not been fully studied in hereditary neuropathies, and it is not known whether these measures distinguish hereditary from acquired demyelination. We compared DCMAP duration and P-D CMAP dispersion in 91 genetically characterized hereditary neuropathies and 33 subjects with CIDP. DCMAP dispersion was more frequent in nerves affected by CIDP (41.5%) than in Charcot-Marie-Tooth disease (CMT)1A (24.4%), CMT1B (7.4%), hereditary neuropathy with liability to pressure palsies (HNPP) (10.5%), or CMTX (9.8%). P-D CMAP dispersion was more frequent in CIDP (27.7% of nerves) than in hereditary neuropathies (16.3%) when applying American Academy of Neurology (AAN) criteria; however, its frequency was similar in CIDP and the hereditary neuropathies using the more restrictive criteria of the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM). Although dispersion is more common in CIDP than in the hereditary neuropathies, DCMAP and P-D dispersion occur in at least one motor nerve in a significant proportion of hereditary neuropathies, and cannot be used in isolation to distinguish acquired from hereditary demyelination.

  19. 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.

  20. 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.

  1. Effect of thermal acclimation on action potentials and sarcolemmal K+ channels from Pacific bluefin tuna cardiomyocytes.

    Science.gov (United States)

    Galli, G L J; Lipnick, M S; Block, B A

    2009-08-01

    To sustain cardiac muscle contractility relatively independent of temperature, some fish species are capable of temporarily altering excitation-contraction coupling processes to meet the demands of their environment. The Pacific bluefin tuna, Thunnus orientalis, is a partially endothermic fish that inhabits a wide range of thermal niches. The present study examined the effects of temperature and thermal acclimation on sarcolemmal K(+) currents and their role in action potential (AP) generation in bluefin tuna cardiomyocytes. Atrial and ventricular myocytes were enzymatically isolated from cold (14 degrees C)- and warm (24 degrees C)-acclimated bluefin tuna. APs and current-voltage relations of K(+) channels were measured using the whole cell current and voltage clamp techniques, respectively. Data were collected either at the cardiomyocytes' respective acclimation temperature of 14 or 24 degrees C or at a common test temperature of 19 degrees C (to reveal the effects of acclimation). AP duration (APD) was prolonged in cold-acclimated (CA) cardiomyocytes tested at 14 degrees C compared with 19 degrees C and in warm-acclimated (WA) cardiomyocytes tested at 19 degrees C compared with 24 degrees C. This effect was mirrored by a decrease in the density of the delayed-rectifier current (I(Kr)), whereas the density of the background inward-rectifier current (I(K1)) was unchanged. When CA and WA cardiomyocytes were tested at a common temperature of 19 degrees C, no significant effects of temperature acclimation on AP shape or duration were observed, whereas I(Kr) density was markedly increased in CA cardiomyocytes. I(K1) density was unaffected in CA ventricular myocytes but was significantly reduced in CA atrial myocytes, resulting in a depolarization of atrial resting membrane potential. Our results indicate the bluefin AP is relatively short compared with other teleosts, which may allow the bluefin heart to function at cold temperatures without the necessity for thermal

  2. 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.

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

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    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.

  4. Ionic mechanisms maintaining action potential conduction velocity at high firing frequencies in an unmyelinated axon.

    Science.gov (United States)

    Cross, Kevin P; Robertson, R Meldrum

    2016-05-01

    The descending contralateral movement detector (DCMD) is a high-performance interneuron in locusts with an axon capable of transmitting action potentials (AP) at more than 500 Hz. We investigated biophysical mechanisms for fidelity of high-frequency transmission in this axon. We measured conduction velocities (CVs) at room temperature during exposure to 10 mmol/L cadmium, a calcium current antagonist, and found significant reduction in CV with reduction at frequencies >200 Hz of ~10%. Higher temperatures induced greater CV reductions during exposure to cadmium across all frequencies of ~20-30%. Intracellular recordings during 15 min of exposure to cadmium or nickel, also a calcium current antagonist, revealed an increase in the magnitude of the afterhyperpolarization potential (AHP) and the time to recover to baseline after the AHP (Medians for Control: -19.8%; Nickel: 167.2%; Cadmium: 387.2%), that could be due to a T-type calcium current. However, the removal of extracellular calcium did not mimic divalent cation exposure suggesting calcium currents are not the cause of the AHP increase. Computational modeling showed that the effects of the divalent cations could be modeled with a persistent sodium current which could be blocked by high concentrations of divalent cations. Persistent sodium current shortened the AHP duration in our models and increased CV for high-frequency APs. We suggest that faithful, high-frequency axonal conduction in the DCMD is enabled by a mechanism that shortens the AHP duration like a persistent or resurgent sodium current.

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

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    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.

  6. 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.

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

    OpenAIRE

    Donald Kerwin; Robert Warren

    2016-01-01

    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 ...

  8. 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.

  9. Evidence for potential bias in the Health and Activity Limitation Index as a health preference measure for persons with disabilities.

    Science.gov (United States)

    Boslaugh, Sarah E; Andresen, Elena M; Recktenwald, Angela; Gillespie, Kathleen

    2009-01-01

    The American public health plan Healthy People 2010 sets overall goals based on utility-linked information from the Health and Activity Limitation Index (HALex). However, little is known about how utilities measured by the HALex compare with those from established gold standard preference-based utility measures. In addition, distribution of HALex values from the general population underrepresents the experience of persons with disability, leading to uncertain interpretation of their utility values. Therefore, we sought to report the validity and interpretation of HALex scores compared to scores from a preference-based health-related quality of life measure, the Quality of Well-Being (QWB) scale. A telephone survey with component measures was administered in random order. Participants consisted of 401 adults from a large Midwest metropolitan area: 302 were selected by random-digit-dial methodology and 99 were volunteers with mobility impairment extending the disability values of the sample. Multiple regression analysis predicted HALex scores from QWB scores and from demographic and self-reported health characteristics. QWB scores accounted for 41% of the variance in HALex scores. The addition of five demographic and health factors increased the variance explained to 63%. Scores on the QWB and HALex were similar on mid-range values and discrepant at the extremes; that is, persons with extreme HALex scores tended to have more moderate QWB scores. HALex scores were higher for white adults than predicted by their QWB scores and lower for people with chronic diseases and disabilities. Utilities as measured by the HALex and QWB can differ markedly, particularly if the person is classified at either end of the spectrum of function. Of similar concern is that fact that HALex scores show a systematic bias in relationship to QWB scores depending on a person's demographic and health-related characteristics.

  10. Calcium-sensitive action potential of long duration in the fertilized egg of the ctenophore Mnemiopsis leidyi.

    Science.gov (United States)

    Barish, M E

    1984-09-01

    The membrane properties of fertilized eggs of the ctenophore Mnemiopsis leidyi were studied using standard microelectrode techniques. The resting potential was approximately -80 mV, and was dependent on the extracellular K concentration. Depolarizing current injections elicited an action potential with an initial peak amplitude of +20 to +40 mV (duration about 5 sec) and a long lasting (duration 3 to 10 min) plateau phase. The depolarizing phase and the plateau phase appeared to have different ionic mechanisms. The entire action potential could be prevented by removal of extracellular Ca, but only the amplitude of the depolarizing phase, not the plateau phase, was dependent on the extracellular Ca concentration. The plateau phase was not observed in the absence of Ca, but in the presence of Ca its duration was dependent on the external Ca concentration. The data suggest that the plateau phase is activated as a consequence of Ca influx during the initial depolarizing phase. Removal of external Na resulted in only minor changes in the waveform of repolarization. The action potential was resistant to low concentrations of Mn and Cd in the presence of Ca. The role of this action potential in ctenophore development is not known, but in its waveform and duration it resembles the sperm-gated potentials that have been seen in eggs of other phyla. These experiments show ctenophore embryos to be excitable at very early stages, and suggest their utility in the study of the differentiation of cellular electrical properties.

  11. Resilient RTN fast spiking in Kv3.1 null mice suggests redundancy in the action potential repolarization mechanism.

    Science.gov (United States)

    Porcello, Darrell M; Ho, Chi Shun; Joho, Rolf H; Huguenard, John R

    2002-03-01

    Fast spiking (FS), GABAergic neurons of the reticular thalamic nucleus (RTN) are capable of firing high-frequency trains of brief action potentials, with little adaptation. Studies in recombinant systems have shown that high-voltage-activated K(+) channels containing the Kv3.1 and/or Kv3.2 subunits display biophysical properties that may contribute to the FS phenotype. Given that RTN expresses high levels of Kv3.1, with little or no Kv3.2, we tested whether this subunit was required for the fast action potential repolarization mechanism essential to the FS phenotype. Single- and multiple-action potentials were recorded using whole-cell current clamp in RTN neurons from brain slices of wild-type and Kv3.1-deficient mice. At 23 degrees C, action potentials recorded from homozygous Kv3.1 deficient mice (Kv3.1(-/-)) compared with their wild-type (Kv3.1(+/+)) counterparts had reduced amplitudes (-6%) and fast after-hyperpolarizations (-16%). At 34 degrees C, action potentials in Kv3.1(-/-) mice had increased duration (21%) due to a reduced rate of repolarization (-30%) when compared with wild-type controls. Action potential trains in Kv3.1(-/-) were associated with a significantly greater spike decrement and broadening and a diminished firing frequency versus injected current relationship (F/I) at 34 degrees C. There was no change in either spike count or maximum instantaneous frequency during low-threshold Ca(2+) bursts in Kv3.1(-/-) RTN neurons at either temperature tested. Our findings show that Kv3.1 is not solely responsible for fast spikes or high-frequency firing in RTN neurons. This suggests genetic redundancy in the system, possibly in the form of other Kv3 members, which may suffice to maintain the FS phenotype in RTN neurons in the absence of Kv3.1.

  12. Atria selective prolongation by NIP-142, an antiarrhythmic agent, of refractory period and action potential duration in guinea pig myocardium.

    Science.gov (United States)

    Matsuda, Tomoyuki; Takeda, Kentaro; Ito, Mie; Yamagishi, Reiko; Tamura, Miku; Nakamura, Hideki; Tsuruoka, Noriko; Saito, Tomoaki; Masumiya, Haruko; Suzuki, Takeshi; Iida-Tanaka, Naoko; Itokawa-Matsuda, Maho; Yamashita, Toru; Tsuruzoe, Nobutomo; Tanaka, Hikaru; Shigenobu, Koki

    2005-05-01

    NIP-142 is a novel benzopyran compound that was shown to prolong the atrial effective refractory period and terminate experimental atrial fibrillation in the dog. In the present study, we examined the effects of NIP-142 on isolated guinea pig myocardium and on the G-protein-coupled inwardly rectifying potassium channel current (acetylcholine-activated potassium current; I(KACh)) expressed in Xenopus oocytes. NIP-142 (10 and 100 microM) concentration-dependently prolonged the refractory period and action potential duration in the atrium but not in the ventricle. E-4031 and 4-aminopyridine prolonged action potential duration in both left atrium and right ventricle. Prolongation by NIP-142 of the atrial action potential duration was observed at stimulation frequencies between 0.5 and 5 Hz. In contrast, the prolongation by E-4031 was not observed at higher frequencies. Tertiapin, a blocker of I(KACh), prolonged action potential duration in the atrium but not in the ventricle. NIP-142 completely reversed the carbachol-induced shortening of atrial action potential duration. NIP-142 (1 to 100 microM), as well as tertiapin (0.1 to 100 nM), concentration-dependently blocked I(KACh) expressed in Xenopus oocytes; the blockade by NIP-142 was not affected by membrane voltage. In conclusion, NIP-142 was shown to prolong atrial refractory period and action potential duration through blockade of I(KACh) which may possibly explain its previously described antiarrhythmic activity. NIP-142 has pharmacological properties that are different from classical class III antiarrhythmic agents such as atria specificity and lack of reverse frequency dependence, and thus appears promising for the treatment of supraventricular arrhythmia.

  13. The mitochondrial monoamine oxidase-aldehyde dehydrogenase pathway: a potential site of action of daidzin.

    Science.gov (United States)

    Rooke, N; Li, D J; Li, J; Keung, W M

    2000-11-02

    Recent studies showed that daidzin suppresses ethanol intake in ethanol-preferring laboratory animals. In vitro, it potently and selectively inhibits the mitochondrial aldehyde dehydrogenase (ALDH-2). Further, it inhibits the conversion of monoamines such as serotonin (5-HT) and dopamine (DA) into their respective acid metabolites, 5-hydroxyindole-3-acetic acid (5-HIAA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in isolated hamster or rat liver mitochondria. Studies on the suppression of ethanol intake and inhibition of 5-HIAA (or DOPAC) formation by six structural analogues of daidzin suggested a potential link between these two activities. This, together with the finding that daidzin does not affect the rates of mitochondria-catalyzed oxidative deamination of these monoamines, raised the possibility that the ethanol intake-suppressive (antidipsotropic) action of daidzin is not mediated by the monoamines but rather by their reactive biogenic aldehyde intermediates such as 5-hydroxyindole-3-acetaldehyde (5-HIAL) and/or 3,4-dihydroxyphenylacetaldehyde (DOPAL) which accumulate in the presence of daidzin. To further evaluate this possibility, we synthesized more structural analogues of daidzin and tested and compared their antidipsotropic activities in Syrian golden hamsters with their effects on monoamine metabolism in isolated hamster liver mitochondria using 5-HT as the substrate. Effects of daidzin and its structural analogues on the activities of monoamine oxidase (MAO) and ALDH-2, the key enzymes involved in 5-HT metabolism in the mitochondria, were also examined. Results from these studies reveal a positive correlation between the antidipsotropic activities of these analogues and their abilities to increase 5-HIAL accumulation during 5-HT metabolism in isolated hamster liver mitochondria. Daidzin analogues that potently inhibit ALDH-2 but have no or little effect on MAO are most antidipsotropic, whereas those that also potently inhibit MAO exhibit little, if

  14. 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

  15. Stimulation rate modulates effects of the dihydropyridine CGP 28 392 on cardiac calcium-dependent action potentials.

    OpenAIRE

    Kamp, T. J.; Miller, R. J.; Sanguinetti, M C

    1985-01-01

    Calcium (Ca2+)-dependent action potentials were recorded from 22 mM potassium (K+)-depolarized guinea-pig papillary muscle at several different pacing frequencies in the absence and presence of CGP 28 392 (10 microM), a Ca2+ channel agonist. The maximum upstroke velocity (Vmax) of the slow response action potential was measured to determine relative changes in Ca2+ current as a function of pacing frequency. CGP 28 392 increased Vmax more than two fold at low rates of stimulation (1 or 12 puls...

  16. Improved outcomes in auditory brainstem implantation with the use of near-field electrical compound action potentials.

    Science.gov (United States)

    Mandalà, Marco; Colletti, Liliana; Colletti, Giacomo; Colletti, Vittorio

    2014-12-01

    To compare the outcomes (auditory threshold and open-set speech perception at 48-month follow-up) of a new near-field monitoring procedure, electrical compound action potential, on positioning the auditory brainstem implant electrode array on the surface of the cochlear nuclei versus the traditional far-field electrical auditory brainstem response. Retrospective study. Tertiary referral center. Among the 202 patients with auditory brainstem implants fitted and monitored with electrical auditory brainstem response during implant fitting, 9 also underwent electrical compound action potential recording. These subjects were matched retrospectively with a control group of 9 patients in whom only the electrical auditory brainstem response was recorded. Electrical compound action potentials were obtained using a cotton-wick recording electrode located near the surface of the cochlear nuclei and on several cranial nerves. Significantly lower potential thresholds were observed with the recording electrode located on the cochlear nuclei surface compared with the electrical auditory brainstem response (104.4 ± 32.5 vs 158.9 ± 24.2, P = .0030). Electrical brainstem response and compound action potentials identified effects on the neighboring cranial nerves on 3.2 ± 2.4 and 7.8 ± 3.2 electrodes, respectively (P = .0034). Open-set speech perception outcomes at 48-month follow-up had improved significantly in the near- versus far-field recording groups (78.9% versus 56.7%; P = .0051). Electrical compound action potentials during auditory brainstem implantation significantly improved the definition of the potential threshold and the number of auditory and extra-auditory waves generated. It led to the best coupling between the electrode array and cochlear nuclei, significantly improving the overall open-set speech perception. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

  17. Conopressin affects excitability, firing, and action potential shape through stimulation of transient and persistent inward currents in mulluscan neurons.

    Science.gov (United States)

    van Soest, P F; Kits, K S

    1998-04-01

    The molluscan vasopressin/oxytocin-related neuropeptide conopressin activates two persistent inward currents in neurons from the anterior lobe of the right cerebral ganglion of Lymnaea stagnalis that are involved in the control of male copulatory behavior. The low-voltage-activated (LVA) current is activated at a wide range of membrane potentials, its amplitude being only weakly voltage dependent. The high-voltage-activated (HVA) current is activated at potentials positive to -40 mV only and shows a steep voltage dependence. Occurrence of both currents varies from cell to cell, some expressing both and others only the HVA current. In most neurons that have the LVA current, a conopressin-independent persistent inward current (INSR) is found that resembles the HVA current in its voltage dependence. The functional importance of the LVA and HVA currents was studied under current-clamp conditions in isolated anterior lobe neurons. In cells exhibiting both current types, the effect of activation of the LVA current alone was investigated as follows: previously recorded LVA current profiles were injected into the neurons, and the effects were compared with responses induced by conopressin. Both treatments resulted in a strong depolarization and firing activity. No differences in firing frequency and burst duration were observed, indicating that activation of the LVA current is sufficient to evoke bursts. In cells exhibiting only the HVA current, the effect of conopressin on the response to a depolarizing stimulus was tested. Conopressin reversibly increased the number of action potentials generated by the stimulus, suggesting that the HVA current enhances excitability and counteracts accommodation. Conopressin enhanced action potential broadening during depolarizing stimuli in many neurons. Voltage-clamp experiments performed under ion-selective conditions revealed the presence of transient sodium and calcium currents. Using the action potential clamp technique, it was

  18. Ionic basis of the different action potential configurations of single guinea-pig atrial and ventricular myocytes.

    Science.gov (United States)

    Hume, J R; Uehara, A

    1985-11-01

    Single myocardial cells were enzymatically dispersed from guinea-pig atria and ventricles. At 25 degrees C, atrial cell action potentials differed significantly from ventricular cell action potentials in duration (atrial = 141 ms, ventricular = 497 ms) and over-shoot (atrial = +36 mV, ventricular = +42 mV). Action potentials of atrial and ventricular cells responded differently to changes in external K+ concentration ([K+]o). Elevation of [K+]o from 6 to 11 mM depolarized atrial cells but produced no significant change in action potential duration; similar changes in [K+]o depolarized ventricular cells and produced a significant shortening of the action potential duration. Voltage-clamp experiments were performed to investigate the ionic basis underlying the different action potential configurations of single atrial and ventricular myocytes. A single-micropipette voltage-clamp technique was used, employing either extremely small-tip diameter pipettes, without internal cell dialysis (Hume & Giles, 1983), or larger tip diameter pipettes, with internal dialysis (Hamill, Marty, Neher, Sakmann & Sigworth, 1981). Two significant differences in background K+ conductance in single atrial and ventricular myocytes were observed: (i) the isochronal (5 s) current-voltage relationship of single ventricular myocytes exhibited a region of prominent negative slope conductance and elevation of [K+]o produced cross-over; a negative slope conductance region was absent in atrial cells and elevation of [K+]o produced very little cross-over of isochronal current-voltage relationships, and (ii) hyperpolarizing voltage pulses applied from holding potentials of -50 mV elicited inward current in ventricular cells which decayed with time; similar voltage-clamp pulses in atrial cells elicited inward currents which fail to decay. Single K+ channel current measurements confirmed the existence of different resting K+ channel properties in single atrial and ventricular myocytes. Resting K

  19. Developmental impairment of compound action potential in the optic nerve of myelin mutant taiep rats.

    Science.gov (United States)

    Roncagliolo, Manuel; Schlageter, Carol; León, Claudia; Couve, Eduardo; Bonansco, Christian; Eguibar, José R

    2006-01-05

    The taiep rat is a myelin mutant with an initial hypomyelination, followed by a progressive demyelination of the CNS. The neurological correlates start with tremor, followed by ataxia, immobility episodes, epilepsy and paralysis. The optic nerve, an easily-isolable central tract fully myelinated by oligodendrocytes, is a suitable preparation to evaluate the developmental impairment of central myelin. We examined the ontogenic development of optic nerve compound action potentials (CAP) throughout the first 6 months of life of control and taiep rats. Control optic nerves (ON) develop CAPs characterized by three waves. Along the first month, the CAPs of taiep rats showed a delayed maturation, with lower amplitudes and longer latencies than controls; at P30, the conduction velocity has only a third of the normal value. Later, as demyelination proceeds, the conduction velocity of taiep ONs begins to decrease and CAPs undergo a gradual temporal dispersion. CAPs of control and taiep showed differences in their pharmacological sensitivity to TEA and 4-AP, two voltage dependent K+ channel-blockers. As compared with TEA, 4-AP induced a significant increase of the amplitudes and a remarkable broadening of CAPs. After P20, unlike controls, the greater sensitivity to 4-AP exhibited by taiep ONs correlates with the detachment and retraction of paranodal loops suggesting that potassium conductances could regulate the excitability as demyelination of CNS axons progresses. It is concluded that the taiep rat, a long-lived mutant, provides a useful model to study the consequences of partial demyelination and the mechanisms by which glial cells regulate the molecular organization and excitability of axonal membranes during development and disease.

  20. 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.

  1. Action potential processing in a detailed Purkinje cell model reveals a critical role for axonal compartmentalization

    Directory of Open Access Journals (Sweden)

    Stefano eMasoli

    2015-02-01

    Full Text Available The Purkinje cell (PC is among the most complex neurons in the brain and plays a critical role for cerebellar functioning. PCs operate as fast pacemakers modulated by synaptic inputs but can switch from simple spikes to complex bursts and, in some conditions, show bistability. In contrast to original works emphasizing dendritic Ca-dependent mechanisms, recent experiments have supported a primary role for axonal Na-dependent processing, which could effectively regulate spike generation and transmission to deep cerebellar nuclei (DCN. In order to account for the numerous ionic mechanisms involved (at present including Nav1.6, Cav2.1, Cav3.1, Cav3.2, Cav3.3, Kv1.1, Kv1.5, Kv3.3, Kv3.4, Kv4.3, KCa1.1, KCa2.2, KCa3.1, Kir2.x, HCN1, we have elaborated a multicompartmental model incorporating available knowledge on localization and gating of PC ionic channels. The axon, including initial segment (AIS and Ranvier nodes (RNs, proved critical to obtain appropriate pacemaking and firing frequency modulation. Simple spikes initiated in the AIS and protracted discharges were stabilized in the soma through Na-dependent mechanisms, while somato-dendritic Ca channels contributed to sustain pacemaking and to generate complex bursting at high discharge regimes. Bistability occurred only following Na and Ca channel down-regulation. In addition, specific properties in RNs K currents were required to limit spike transmission frequency along the axon. The model showed how organized electroresponsive functions could emerge from the molecular complexity of PCs and showed that the axon is fundamental to complement ionic channel compartmentalization enabling action potential processing and transmission of specific spike patterns to DCN.

  2. 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

    2015-04-01

    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 Ca(2+) 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 Ca(2+) transients, with a further Ca(2+) 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 Ca(2+) signals suggest changes in excitability and remodeling of the global Ca(2+) 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. © 2015 The Authors. Physiological Reports published by Wiley

  3. A potential role for cannabinoid receptors in the therapeutic action of fenofibrate.

    Science.gov (United States)

    Priestley, Richard S; Nickolls, Sarah A; Alexander, Stephen P H; Kendall, David A

    2015-04-01

    Cannabinoids are reported to have actions through peroxisome proliferator-activated receptors (PPARs), which led us to investigate PPAR agonists for activity at the cannabinoid receptors. Radio-ligand binding and functional assays were conducted using human recombinant cannabinoid type 1 (CB1) or cannabinoid type 2 (CB2) receptors, as well as the guinea pig isolated ileum, using the full agonist CP55940 as a positive control. The PPAR-α agonist fenofibrate exhibited submicromolar affinity for both receptors (pKi CB1, 6.3 ± 0.1; CB2, 7.7 ± 0.1). Functionally, fenofibrate acted as an agonist at the CB2 receptor (pEC50, 7.7 ± 0.1) and a partial agonist at the CB1 receptor, although with a decrease in functional response at higher concentrations, producing bell-shaped concentration-response curves. High concentrations of fenofibrate were able to increase the dissociation rate constant for [(3)H]-CP55940 at the CB1 receptor, (kfast without: 1.2 ± 0.2/min; with: 3.8 ± 0.1 × 10(-2)/min) and decrease the maximal response to CP55940 (Rmax, 86 ± 2%), which is consistent with a negative allosteric modulator. Fenofibrate also reduced electrically induced contractions in isolated guinea pig ileum via CB1 receptors (pEC50, 6.0 ± 0.4). Fenofibrate is thus identified as an example of a new class of cannabinoid receptor ligand and allosteric modulator, with the potential to interact therapeutically with cannabinoid receptors in addition to its primary PPAR target. © FASEB.

  4. The ionic bases of the action potential in isolated mouse cardiac Purkinje cell.

    Science.gov (United States)

    Vaidyanathan, Ravi; O'Connell, Ryan P; Deo, Makarand; Milstein, Michelle L; Furspan, Philip; Herron, Todd J; Pandit, Sandeep V; Musa, Hassan; Berenfeld, Omer; Jalife, José; Anumonwo, Justus M B

    2013-01-01

    Collecting electrophysiological and molecular data from the murine conduction system presents technical challenges. Thus, only little advantage has been taken of numerous genetically engineered murine models to study excitation through the cardiac conduction system of the mouse. To develop an approach for isolating murine cardiac Purkinje cells (PCs), to characterize major ionic currents and to use the data to simulate action potentials (APs) recorded from PCs. Light microscopy was used to isolate and identify PCs from apical and septal cells. Current and voltage clamp techniques were used to record APs and whole cell currents. We then simulated a PC AP on the basis of our experimental data. APs recorded from PCs were significantly longer than those recorded from ventricular cells. The prominent plateau phase of the PC AP was very negative (≈-40 mV). Spontaneous activity was observed only in PCs. The inward rectifier current demonstrated no significant differences compared to ventricular myocytes (VMs). However, sodium current density was larger, and the voltage-gated potassium current density was significantly less in PCs compared with myocytes. T-type Ca(2+) currents (I(Ca,T)) were present in PCs but not VMs. Computer simulations suggest that I(Ca,T) and cytosolic calcium diffusion significantly modulate AP profile recorded in PCs, as compared to VMs. Our study provides the first comprehensive ionic profile of murine PCs. The data show unique features of PC ionic mechanisms that govern its excitation process. Experimental data and numerical modeling results suggest that a smaller voltage-gated potassium current and the presence of I(Ca,T) are important determinants of the longer and relatively negative plateau phase of the APs. Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  5. Dynamics of the late Na(+) current during cardiac action potential and its contribution to afterdepolarizations.

    Science.gov (United States)

    Horvath, Balazs; Banyasz, Tamas; Jian, Zhong; Hegyi, Bence; Kistamas, Kornel; Nanasi, Peter P; Izu, Leighton T; Chen-Izu, Ye

    2013-11-01

    The objective of this work is to examine the contribution of late Na(+) current (INa,L) to the cardiac action potential (AP) and arrhythmogenic activities. In spite of the rapidly growing interest toward this current, there is no publication available on experimental recording of the dynamic INa,L current as it flows during AP with Ca(2+) cycling. Also unknown is how the current profile changes when the Ca(2+)-calmodulin dependent protein kinase II (CaMKII) signaling is altered, and how the current contributes to the development of arrhythmias. In this study we use an innovative AP-clamp Sequential Dissection technique to directly record the INa,L current during the AP with Ca(2+) cycling in the guinea pig ventricular myocytes. First, we found that the magnitude of INa,L measured under AP-clamp is substantially larger than earlier studies indicated. CaMKII inhibition using KN-93 significantly reduced the current. Second, we recorded INa,L together with IKs, IKr, and IK1 in the same cell to understand how these currents counterbalance to shape the AP morphology. We found that the amplitude and the total charge carried by INa,L exceed that of IKs. Third, facilitation of INa,L by Anemone toxin II prolonged APD and induced Ca(2+) oscillations that led to early and delayed afterdepolarizations and triggered APs; these arrhythmogenic activities were eliminated by buffering Ca(2+) with BAPTA. In conclusion, INa,L contributes a significantly large inward current that prolongs APD and unbalances the Ca(2+) homeostasis to cause arrhythmogenic APs.

  6. Dynamics of the Late Na+ current during cardiac action potential and its contribution to afterdepolarizations

    Science.gov (United States)

    Horvath, Balazs; Banyasz, Tamas; Jian, Zhong; Hegyi, Bence; Kistamas, Kornel; Nanasi, Peter P.; Izu, Leighton T.; Chen-Izu, Ye

    2013-01-01

    The objective of this work is to examine the contribution of late Na+ current (INa,L) to the cardiac action potential (AP) and arrhythmogenic activities. In spite of the rapidly growing interest toward this current, there is no publication available on experimental recording of the dynamic INa,L current as it flows during AP with Ca2+ cycling. Also unknown is how the current profile changes when the Ca2+-calmodulin dependent protein kinase II (CaMKII) signaling is altered, and how the current contributes to the development of arrhythmias. In this study we use an innovative AP-clamp Sequential Dissection technique to directly record the INa,L current during the AP with Ca2+ cycling in the guinea pig ventricular myocytes. First, we found that the magnitude of INa,L measured under AP-clamp is substantially larger than earlier studies indicated. CaMKII inhibition using KN-93 significantly reduced the current. Second, we recorded INa,L together with IKs, IKr, and IK1 in the same cell to understand how these currents counterbalance to shape the AP morphology. We found that the amplitude and the total charge carried by INa,L exceed that of IKs. Third, facilitation of INa,L by Anemone toxin II prolonged APD and induced Ca2+ oscillations that led to early and delayed afterdepolarizations and triggered APs; these arrhythmogenic activities were eliminated by buffering Ca2+ with BAPTA. In conclusion, INa,L contributes a significantly large inward current that prolongs APD and unbalances the Ca2+ homeostasis to cause arrhythmogenic APs. PMID:24012538

  7. Beta-adrenergic stimulation reverses the IKr–IKs dominant pattern during cardiac action potential

    Science.gov (United States)

    Banyasz, Tamas; Jian, Zhong; Horvath, Balazs; Khabbaz, Shaden; Izu, Leighton T.; Chen-Izu, Ye

    2014-01-01

    β-adrenergic stimulation differentially modulates different K+ channels and thus fine-tunes cardiac action potential (AP) repolarization. However, it remains unclear how the proportion of IKs, IKr, and IK1 current in the same cell would be altered by β-adrenergic stimulation, which would change the relative contribution of individual K+ current to the total repolarization reserve. In this study we used an innovative AP-clamp Sequential Dissection technique to directly record the dynamic –IKs, IKr, IK1– currents during the AP in guinea pig ventricular myocytes under physiologically relevant conditions. Our data provide quantitative measures of the magnitude and time course of IKs, IKr, IK1 currents in the same cell under its own steady-state AP, in a physiological milieu, and with preserved Ca2+ homeostasis. We found that isoproterenol treatment significantly enhanced IKs, moderately increased IK1, but slightly decreased IKr in a dose-dependent manner. The dominance pattern of the K+ currents was IKr>IK1>IKs at the control condition, but reversed to IKr

  8. Encoding of High Frequencies Improves with Maturation of Action Potential Generation in Cultured Neocortical Neurons

    Science.gov (United States)

    Nikitin, Evgeny S.; Bal, Natalia V.; Malyshev, Aleksey; Ierusalimsky, Victor N.; Spivak, Yulia; Balaban, Pavel M.; Volgushev, Maxim

    2017-01-01

    The ability of neocortical neurons to detect and encode rapid changes at their inputs is crucial for basic neuronal computations, such as coincidence detection, precise synchronization of activity and spike-timing dependent plasticity. Indeed, populations of cortical neurons can respond to subtle changes of the input very fast, on a millisecond time scale. Theoretical studies and model simulations linked the encoding abilities of neuronal populations to the fast onset dynamics of action potentials (APs). Experimental results support this idea, however mechanisms of fast onset of APs in cortical neurons remain elusive. Studies in neuronal cultures, that are allowing for accurate control over conditions of growth and microenvironment during the development of neurons and provide better access to the spike initiation zone, may help to shed light on mechanisms of AP generation and encoding. Here we characterize properties of AP encoding in neocortical neurons grown for 11–25 days in culture. We show that encoding of high frequencies improves upon culture maturation, which is accompanied by the development of passive electrophysiological properties and AP generation. The onset of APs becomes faster with culture maturation. Statistical analysis using correlations and linear model approaches identified the onset dynamics of APs as a major predictor of age-dependent changes of encoding. Encoding of high frequencies strongly correlated also with the input resistance of neurons. Finally, we show that maturation of encoding properties of neurons in cultures is similar to the maturation of encoding in neurons studied in slices. These results show that maturation of AP generators and encoding is, to a large extent, determined genetically and takes place even without normal micro-environment and activity of the whole brain in vivo. This establishes neuronal cultures as a valid experimental model for studying mechanisms of AP generation and encoding, and their maturation. PMID

  9. 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.

    2016-01-01

    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 Ca2+ 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 Ca2+ 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 Ca2+-activation of large conductance calcium-activated potassium (BK) and small conductance calcium-activated potassium (SK) channels in these events. In conclusion, the reduced Ca2+ 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 Ca2+ and ATP together to control life and death’. PMID:27377724

  10. 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

    The small intestine of W/Wv mice lacks both the network of interstitial cells of Cajal (ICC), associated with Auerbach's plexus, and pacemaker activity, i.e., it does not generate slow-wave-type action potentials. The W/Wv muscle preparations showed a wide variety of electrical activities, rangin...

  11. 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...

  12. Synthesis of a dendritic estrogen cluster: A potential tool for studies of nuclear versus extranuclear pathways of estrogen actions

    Institute of Scientific and Technical Information of China (English)

    Jian Chen; Hu Zheng; Yan Song; Yu Feng Liang; Qing Rong Qi

    2012-01-01

    A novel estrogen dendrimer has been synthesized through a combination of divergent and convergent approaches in 9 practical steps and in good yields.It was characterized and confirmed by elemental analysis,FT-IR,MS,1H NMR,13C NMR.The dendrimer contains 16 estrone units and is potentially a useful tool for the studies of estrogen actions.

  13. 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

  14. Genetic structure and rabies spread potential in raccoons: the role of landscape barriers and sex-biased dispersal.

    Science.gov (United States)

    Côté, Héloïse; Garant, Dany; Robert, Karine; Mainguy, Julien; Pelletier, Fanie

    2012-06-01

    Identifying natural barriers to movements of hosts associated with infectious diseases is essential for developing effective control strategies. Raccoon rabies variant (RRV) is a zoonosis of concern for humans because its main vector, the raccoon (Procyon lotor), is found near residential areas. In Québec, Canada, all cases of RRV found in raccoons since 2006 were detected on the eastern side of the Richelieu River, suggesting that this river acts as a barrier to gene flow and thus the potential for RRV to spread. The objectives of this study were to characterize the genetic structure of raccoon populations and assess the effect of the Richelieu River on the population structure in southern Québec, Canada. We also evaluated whether RRV spread potential differed between sex and at a larger spatial scale. Our analyses revealed a weak signal of genetic differentiation among individuals located on each side of the Richelieu River. At a larger spatial scale, genetic structuring was weak. Our results suggest that rivers might not always efficiently restrain raccoon movements and spread of RRV. We suggest that the difference in genetic structure found between sexes can be partly explained by male movements during the breeding season in winter, when ice bridges allow passage over most rivers in Québec.

  15. The afterhyperpolarizing potential following a train of action potentials is suppressed in an acute epilepsy model in the rat Cornu Ammonis 1 area.

    Science.gov (United States)

    Kernig, K; Kirschstein, T; Würdemann, T; Rohde, M; Köhling, R

    2012-01-10

    In hippocampal Cornu Ammonis 1 (CA1) neurons, a prolonged depolarization evokes a train of action potentials followed by a prominent afterhyperpolarizing potential (AHP), which critically dampens neuronal excitability. Because it is not known whether epileptiform activity alters the AHP and whether any alteration of the AHP is independent of inhibition, we acutely induced epileptiform activity by bath application of the GABA(A) receptor blocker gabazine (5 μM) in the rat hippocampal slice preparation and studied its impact on the AHP using intracellular recordings. Following 10 min of gabazine wash-in, slices started to develop spontaneous epileptiform discharges. This disinhibition was accompanied by a significant shift of the resting membrane potential of CA1 neurons to more depolarized values. Prolonged depolarizations (600 ms) elicited a train of action potentials, the number of which was not different between baseline and gabazine treatment. However, the AHP following the train of action potentials was significantly reduced after 20 min of gabazine treatment. When the induction of epileptiform activity was prevented by co-application of 6-cyano-7-nitroquinoxaline-2,3-dione disodium (CNQX, 10 μM) and D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5, 50 μM) to block α-amino-3-hydroxy-5-methylisoxazolepropionate (AMPA) and N-methyl-d-aspartate (NMDA) receptors, respectively, the AHP was preserved despite of GABA(A) receptor inhibition suggesting that the epileptiform activity was required to suppress the AHP. Moreover, the AHP was also preserved when the slices were treated with the protein kinase blockers H-9 (100 μM) and H-89 (1 μM). These results demonstrate that the AHP following a train of action potentials is rapidly suppressed by acutely induced epileptiform activity due to a phosphorylation process-presumably involving protein kinase A.

  16. Inhibitors of protein kinase C prevent enhancement of calcium current and action potentials in peptidergic neurons of Aplysia.

    Science.gov (United States)

    Conn, P J; Strong, J A; Kaczmarek, L K

    1989-02-01

    Following brief stimulation of an afferent pathway, the bag cell neurons of Aplysia undergo a dramatic change in excitability, resulting in a prolonged discharge of spontaneous action potentials. During the discharge, the action potentials of the bag cell neurons become enhanced in height and width. The afterdischarge triggers release of neuroactive peptides that initiate egg-laying behavior in this animal. Evidence suggests that changes in excitability of the bag cell neurons may be mediated by activation of protein kinase C (PKC) and cAMP-dependent protein kinase (cAMP-PK). PKC activators, such as the phorbol ester TPA (12-O-tetradecanoyl-13-phorbol acetate), enhance the amplitude of action potentials in isolated bag cell neurons in cell culture. These agents act by unmasking a previously covert species of voltage-dependent calcium channel resulting in an increase in calcium current. In the accompanying paper (Conn et al., 1989), we showed that H-7, a protein kinase inhibitor, inhibits the effect of TPA, and is a selective inhibitor of PKC relative to cAMP-PK in these cells. We now report that another PKC inhibitor, sphinganine, also inhibits the effect of TPA on action potential height and calcium current in cultured bag cell neurons, and that N-acetylsphinganine, an inactive sphinganine analog, fails to inhibit the effects of PKC activators. Although both H-7 and sphinganine prevent the effects of TPA when added prior to TPA addition, neither compound reverses the effects of TPA when added after the action potentials have already become enhanced by TPA.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Evaluation of the continuous rate of supply lead-210 sediment age model: Two sources of potential bias and implications for carbon burial rates

    Science.gov (United States)

    Gonneea, M. E.; Kroeger, K. D.

    2016-12-01

    The past century has been a period of rapid environmental change and ecosystem response to this change is of great interest, particularly in coastal wetlands. Lead-210 is an important sediment chronometer that yields accurate dates over the past century in sediments typically considered too young for carbon-14 dates. Since originally proposed by Appleby and Oldfield in 1978, sediments from a wide range of environments, including salt marshes and mangroves, have been dated with the lead-210 continuous rate of supply (CRS) age model. The power of this model is that it allows ages and accretion rates to be calculated for each interval with measured 210Pb activity, as opposed to a single accretion rate using the constant initial concentration model. There are two sources of potential bias in the model as it is applied to real 210Pb sediment profiles. First, the formulation originally proposed to calculate the mass accretion rate is sensitive to the thickness of sediment sampling intervals, and results in underestimation of mass accretion rates at typical (1 to 2 cm) sampling intervals. Such underestimation is greatest for large intervals and small accretion rates. For example, 1 cm intervals would result in 15% and 2 cm intervals in 22% underestimation for a 1 mm y-1 linear sedimentation rate. Secondly, the continuous rate of supply model requires integration of the total 210Pb profile; failure to measure the entire profile results in calculated ages that are too old and accretion rates that are too low. We propose that 210Pb profiles must be counted to an age of 200 years to avoid this bias within sediments deposited over the past century; profiles integrated to 150 years underestimate accretion rates by 22% at 100 years. It is possible to estimate the sediment concentration of 210Pb at 200 years as a function of 210Pb supply from the atmosphere, sedimentation rate and dry bulk density. Using published core data, we demonstrate that it is particularly important to

  18. Intention seekers: conspiracist ideation and biased attributions of intentionality.

    Directory of Open Access Journals (Sweden)

    Robert Brotherton

    Full Text Available Conspiracist beliefs are widespread and potentially hazardous. A growing body of research suggests that cognitive biases may play a role in endorsement of conspiracy theories. The current research examines the novel hypothesis that individuals who are biased towards inferring intentional explanations for ambiguous actions are more likely to endorse conspiracy theories, which portray events as the exclusive product of intentional agency. Study 1 replicated a previously observed relationship between conspiracist ideation and individual differences in anthropomorphisation. Studies 2 and 3 report a relationship between conspiracism and inferences of intentionality for imagined ambiguous events. Additionally, Study 3 again found conspiracist ideation to be predicted by individual differences in anthropomorphism. Contrary to expectations, however, the relationship was not mediated by the intentionality bias. The findings are discussed in terms of a domain-general intentionality bias making conspiracy theories appear particularly plausible. Alternative explanations are suggested for the association between conspiracism and anthropomorphism.

  19. Proactive inhibitory control: A general biasing account.

    Science.gov (United States)

    Elchlepp, Heike; Lavric, Aureliu; Chambers, Christopher D; Verbruggen, Frederick

    2016-05-01

    Flexible behavior requires a control system that can inhibit actions in response to changes in the environment. Recent studies suggest that people proactively adjust response parameters in anticipation of a stop signal. In three experiments, we tested the hypothesis that proactive inhibitory control involves adjusting both attentional and response settings, and we explored the relationship with other forms of proactive and anticipatory control. Subjects responded to the color of a stimulus. On some trials, an extra signal occurred. The response to this signal depended on the task context subjects were in: in the 'ignore' context, they ignored it; in the 'stop' context, they had to withhold their response; and in the 'double-response' context, they had to execute a secondary response. An analysis of event-related brain potentials for no-signal trials in the stop context revealed that proactive inhibitory control works by biasing the settings of lower-level systems that are involved in stimulus detection, action selection, and action execution. Furthermore, subjects made similar adjustments in the double-response and stop-signal contexts, indicating an overlap between various forms of proactive action control. The results of Experiment 1 also suggest an overlap between proactive inhibitory control and preparatory control in task-switching studies: both require reconfiguration of task-set parameters to bias or alter subordinate processes. We conclude that much of the top-down control in response inhibition tasks takes place before the inhibition signal is presented.

  20. Layer I neurons of rat neocortex. I. Action potential and repetitive firing properties.

    Science.gov (United States)

    Zhou, F M; Hablitz, J J

    1996-08-01

    1. Whole cell patch-clamp techniques, combined with direct visualization of neurons, were used to study action potential (AP) and repetitive firing properties of layer I neurons in slices of rat neocortex. 2. Layer I neurons had resting membrane potentials (RMP) of -59.8 +/- 4.7 mV (mean +/- SD) and input resistances (RN) of 592 +/- 284 M Omega. Layer II/III pyramidal neurons had RMPs and RNs of -61.5 +/- 5.6 mV and 320 +/- 113 M omega, respectively. A double exponential function was needed to describe the charging curves of both neuron types. In layer I neurons, tau(0) was 45 +/- 22 ms and tau(1) was 5 +/- 3.3 ms whereas in layer II/III pyramidal neurons, tau(0) was 41 +/- 11 ms and tau(1) was 3 +/- 2.6 ms. Estimates of specific membrane resistance (Rm) for layer I and layer II/III cells were 45 +/- 22 and 41 +/- 11 k omega cm2, respectively (Cm was assumed to be 1 microF/cm2). 3. AP threshold was -41 +/- 2 mV in layer I neurons. Spike amplitudes, measured from threshold to peak, were 90.6 +/- 7.7 mV. AP durations, measured both at the base and half maximal amplitude, were 2.5 +/- 0.4 and 1.1 +/- 0.2 ms, respectively. AP 10-90% rise and repolarization times were 0.6 +/- 0.1 and 1.1 +/- 0.2 ms, respectively. In layer II/III pyramidal neurons, AP threshold was -41 +/- 2.5 mV and spike amplitude was 97 +/- 9.7 mV. AP duration at base and half maximal amplitude was 5.4 +/- 1.1 ms and 1.8 +/- 0.2 ms, respectively. AP 10-90% rise and decay times were 0.6 +/- 0.1 ms and 2.8 +/- 0.6 ms, respectively. 4. Layer I neurons were fast spiking cells that showed little frequency adaptation, a large fast afterhyperpolarization (fAHP), and no slow afterhyperpolarization (sAHP). Some cells had a medium afterhyperpolarization (mAHP) and a slow afterdepolarization (sADP). All pyramidal cells in layer II/III and "atypical" pyramidal neurons in upper layer II showed regular spiking behavior, prominent frequency adaptation, and marked sAHPs. 5. In both layer I neurons and layer II

  1. Modulation of presynaptic action potential kinetics underlies synaptic facilitation of type B photoreceptors after associative conditioning in Hermissenda.

    Science.gov (United States)

    Gandhi, C C; Matzel, L D

    2000-03-01

    Descriptions of conditioned response generation in Hermissenda stipulate that the synaptic interaction between type B and A photoreceptors should be enhanced after associative pairings of light and rotation. Although evidence from several laboratories has confirmed this assumption, the mechanism underlying this synaptic facilitation has not been elucidated. Here we report that in vitro conditioning (i.e., light paired with stimulation of vestibular hair cells) modifies the kinetics of presynaptic action potentials in the B photoreceptor in a manner sufficient to account for this synaptic facilitation. After paired training, we observed an increase in the duration of evoked action potentials and a decrease in the amplitude of the spike afterhyperpolarization in the B-cell. As previously reported, paired training also enhanced the excitability (i.e., input resistance and evoked spike rate) of the B photoreceptor. In a second experiment, simultaneous recordings were made in type B and A photoreceptors, and paired training was found to produce an increase in the amplitude of the IPSP in the A photoreceptor in response to an evoked spike in the B-cell. Importantly, there was no change in the initial slope of the postsynaptic IPSP in the A photoreceptor, suggesting that spike duration-independent mechanisms of neurotransmitter exocytosis or postsynaptic receptor sensitivity did not contribute to the observed synaptic facilitation. Perfusion of 4-aminopyridine (4-AP) mimicked a known effect of behavioral conditioning in that it specifically reduced the amplitude of the transient voltage-dependent K(+) current (I(A)) in the B-cell, but in addition, produced action potential broadening and synaptic facilitation that was analogous to that observed after in vitro conditioning. Finally, the effect of 4-AP on B-cell action potentials and on the postsynaptic IPSP in the A-cell was occluded by previous paired (but not unpaired) training, suggesting that the prolongation of the B

  2. The own-age bias in face memory is unrelated to differences in attention--evidence from event-related potentials.

    Science.gov (United States)

    Neumann, Markus F; End, Albert; Luttmann, Stefanie; Schweinberger, Stefan R; Wiese, Holger

    2015-03-01

    Participants are more accurate at remembering faces from their own relative to a different age group (the own-age bias, or OAB). A recent socio-cognitive account has suggested that differential allocation of attention to old versus young faces underlies this phenomenon. Critically, empirical evidence for a direct relationship between attention to own- versus other-age faces and the OAB in memory is lacking. To fill this gap, we tested the roles of attention in three different experimental paradigms, and additionally analyzed event-related brain potentials (ERPs). In Experiment 1, we compared the learning of old and young faces during focused versus divided attention, but revealed similar OABs in subsequent memory for both attention conditions. Similarly, manipulating attention during learning did not differentially affect the ERPs elicited by young versus old faces. In Experiment 2, we examined the repetition effects from task-irrelevant old and young faces presented under varying attentional loads on the N250r ERP component as an index of face recognition. Independent of load, the N250r effects were comparable for both age categories. Finally, in Experiment 3 we measured the N2pc as an index of attentional selection of old versus young target faces in a visual search task. The N2pc was not significantly different for the young versus the old target search conditions, suggesting similar orientations of attention to either face age group. Overall, we propose that the OAB in memory is largely unrelated to early attentional processes. Our findings therefore contrast with the predictions from socio-cognitive accounts on own-group biases in recognition memory, and are more easily reconciled with expertise-based models.

  3. 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.

  4. 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, simil

  5. 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

  6. Mode of action of Bacillus thuringiensis Cry and Cyt toxins and their potential for insect control.

    Science.gov (United States)

    Bravo, Alejandra; Gill, Sarjeet S; Soberón, Mario

    2007-03-15

    Bacillus thuringiensis Crystal (Cry) and Cytolitic (Cyt) protein families are a diverse group of proteins with activity against insects of different orders--Lepidoptera, Coleoptera, Diptera and also against other invertebrates such as nematodes. Their primary action is to lyse midgut epithelial cells by inserting into the target membrane and forming pores. Among this group of proteins, members of the 3-Domain Cry family are used worldwide for insect control, and their mode of action has been characterized in some detail. Phylogenetic analyses established that the diversity of the 3-Domain Cry family evolved by the independent evolution of the three domains and by swapping of domain III among toxins. Like other pore-forming toxins (PFT) that affect mammals, Cry toxins interact with specific receptors located on the host cell surface and are activated by host proteases following receptor binding resulting in the formation of a pre-pore oligomeric structure that is insertion competent. In contrast, Cyt toxins directly interact with membrane lipids and insert into the membrane. Recent evidence suggests that Cyt synergize or overcome resistance to mosquitocidal-Cry proteins by functioning as a Cry-membrane bound receptor. In this review we summarize recent findings on the mode of action of Cry and Cyt toxins, and compare them to the mode of action of other bacterial PFT. Also, we discuss their use in the control of agricultural insect pests and insect vectors of human diseases.

  7. Axonal action-potential initiation and Na+ channel densities in the soma and axon initial segment of subicular pyramidal neurons.

    Science.gov (United States)

    Colbert, C M; Johnston, D

    1996-11-01

    A long-standing hypothesis is that action potentials initiate first in the axon hillock/initial segment (AH-IS) region because of a locally high density of Na+ channels. We tested this idea in subicular pyramidal neurons by using patch-clamp recordings in hippocampal slices. Simultaneous recordings from the soma and IS confirmed that orthodromic action potentials initiated in the axon and then invaded the soma. However, blocking Na+ channels in the AH-IS with locally applied tetrodotoxin (TTX) did not raise the somatic threshold membrane potential for orthodromic spikes. TTX applied to the axon beyond the AH-IS (30-60 microm from the soma) raised the apparent somatic threshold by approximately 8 mV. We estimated the Na+ current density in the AH-IS and somatic membranes by using cell-attached patch-clamp recordings and found similar magnitudes (3-4 pA/microm2). Thus, the present results suggest that orthodromic action potentials initiate in the axon beyond the AH-IS and that the minimum threshold for spike initiation of the neuron is not determined by a high density of Na+ channels in the AH-IS region.

  8. 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.

  9. Regenerating mammalian nerve fibres: changes in action potential waveform and firing characteristics following blockage of potassium conductance.

    Science.gov (United States)

    Kocsis, J D; Waxman, S G; Hildebrand, C; Ruiz, J A

    1982-12-22

    Extracellular application of potassium channel blocking agents is known to increase the amplitude and duration of the compound action potential in non-myelinated and demyelinated axons, but not in mature mammalian myelinated fibres. In the present study we used intra-axonal and whole nerve recording techniques to study the effects of the potassium channel blocking agent 4-aminopyridine (4-AP) on regenerating rat nerve fibres. Our results indicate that early regenerating (premyelinated) axons show considerable broadening of the action potential after 4-AP application and late regenerating (myelinated) axons give rise to burst activity following a single stimulus after 4-AP application. 4-AP did not affect spike waveform or firing properties of normal mature sciatic nerve fibres. These results demonstrate the importance of potassium conductance in stabilizing firing properties of myelinated regenerating axons.

  10. On the use of upper extremity proximal nerve action potentials in the localization of focal nerve lesions producing axonotmesis.

    Science.gov (United States)

    White, J C

    1997-09-01

    Ulnar, median, and radial proximal nerve action potentials (PNAPs) were recorded from the axilla and supraclavicularly, with stimulation of the nerves at the elbow or the radial groove, in 30 control subjects for each nerve. In addition to routine nerve conduction studies, wrist to elbow median nerve action potentials were recorded proximal to the lesion in 76 patients with carpal tunnel syndrome of varying degrees of severity to determine the effect that the distal lesion might have on more proximal nerve conduction. Utilizing this information, PNAPs, standard nerve conduction studies, and needle electrode examinations were carried out in patients with focal elbow area nerve or brachial plexus lesions producing axonotmesis. PNAPs confirmed the site of the lesions producing axonotmesis when localization was possible with standard nerve conduction and/or needle electrode studies and were the sole means by which localization of the lesions producing only sensory axonotmesis was accomplished.

  11. Quantum entanglement in the voltage dependent sodium channel can reproduce the salient features of neuronal action potential initiation

    CERN Document Server

    Summhammer, Johann

    2007-01-01

    We investigate the effects of a quantum entanglement regime within an ion conducting molecule (ion channel) of the neuronal plasma membrane on the onset dynamics of propagating nerve pulses (action potentials). In particular, we model the onset parameters of the sodium current in the Hodgkin Huxley equation as three similar but independent probabilistic mechanisms which become quantum entangled. The underlying physics is general and can involve entanglement between various degrees of freedom underlaying ion transition states or 'gating states' during conduction, e.g. Na$^+$ ions in different channel locations, or different 'affinity' states of ions with atoms lining the sub-regions of the channel protein ('filter-states'). We find that the 'quantum corrected' Hodgkin Huxley equation incorporating entangled systems states can reproduce action potential pulses with the critical onset dynamics observed recently in neocortical neurons in vivo by Naundorf et al. [Nature {\\bf 440}, 1060 (20 April 2006)]. Interestin...

  12. A two-variable model robust to pacemaker behaviour for the dynamics of the cardiac action potential.

    Science.gov (United States)

    Corrado, Cesare; Niederer, Steven A

    2016-11-01

    Ionic models with two state variables are routinely used in patient specific electro-physiology simulations due to the small number of parameters to be constrained and their computational tractability. Among these models, the Mitchell and Schaeffer (MS) action potential model is often used in ventricle electro-physiology due to its ability to reproduce the shape of the action potential and its restitution properties. However, for some choices of parameters characterising this ionic model, unwanted pacemaker behaviour is present. The absence of any a priori criterion to exclude unstable parameter combinations affects parameter fitting algorithms, as unphysiological solutions can only be discarded a posteriori. In this paper we propose an adaptation of the MS model that does not exhibit pacemaker behaviour for any combination of the parameters. The robustness to pacemaker behaviour makes this model suitable for inverse problem applications. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Approach-Induced Biases in Human Information Sampling

    Science.gov (United States)

    Hunt, Laurence T.; Rutledge, Robb B.; Malalasekera, W. M. Nishantha; Kennerley, Steven W.; Dolan, Raymond J.

    2016-01-01

    Information sampling is often biased towards seeking evidence that confirms one’s prior beliefs. Despite such biases being a pervasive feature of human behavior, their underlying causes remain unclear. Many accounts of these biases appeal to limitations of human hypothesis testing and cognition, de facto evoking notions of bounded rationality, but neglect more basic aspects of behavioral control. Here, we investigated a potential role for Pavlovian approach in biasing which information humans will choose to sample. We collected a large novel dataset from 32,445 human subjects, making over 3 million decisions, who played a gambling task designed to measure the latent causes and extent of information-sampling biases. We identified three novel approach-related biases, formalized by comparing subject behavior to a dynamic programming model of optimal information gathering. These biases reflected the amount of information sampled (“positive evidence approach”), the selection of which information to sample (“sampling the favorite”), and the interaction between information sampling and subsequent choices (“rejecting unsampled options”). The prevalence of all three biases was related to a Pavlovian approach-avoid parameter quantified within an entirely independent economic decision task. Our large dataset also revealed that individual differences in the amount of information gathered are a stable trait across multiple gameplays and can be related to demographic measures, including age and educational attainment. As well as revealing limitations in cognitive processing, our findings suggest information sampling biases reflect the expression of primitive, yet potentially ecologically adaptive, behavioral repertoires. One such behavior is sampling from options that will eventually be chosen, even when other sources of information are more pertinent for guiding future action. PMID:27832071

  14. Potential pathways of pesticide action on erectile function-a contributory factor in male infertility

    Institute of Scientific and Technical Information of China (English)

    RP Kaur; V Gupta; AF Christopher; P Bansal

    2015-01-01

    One of the important objectives of this manuscript is to focus on the place of erectile dysfunction as an important factor for infertility. The review is about correlating the indiscriminate use of pesticides and to find out and highlight the evidences for mechanism of action of these pesticides for erectile dysfunction and find out the most used and most dangerous pesticide from erectile dysfunction point of view. The review suggests that erectile dysfunction is having a significant place as a causal factor for infertility. Study infers that pesticides are having multiple mechanisms of action through which these cause erectile dysfunction. It also reflects that acetamiprid is having most devastating effect causing erectile dysfunction as it acts through multiple inhibitory pathways. The review successfully highlights the indiscriminate regional use of pesticides.

  15. Microparticles generated by decompression stress cause central nervous system injury manifested as neurohypophysial terminal action potential broadening

    OpenAIRE

    Yang, Ming; Kosterin, Paul; Salzberg, Brian M.; Milovanova, Tatyana N.; Bhopale, Veena M.; Thom, Stephen R.

    2013-01-01

    The study goal was to use membrane voltage changes during neurohypophysial action potential (AP) propagation as an index of nerve function to evaluate the role that circulating microparticles (MPs) play in causing central nervous system injury in response to decompression stress in a murine model. Mice studied 1 h following decompression from 790 kPa air pressure for 2 h exhibit a 45% broadening of the neurohypophysial AP. Broadening did not occur if mice were injected with the MP lytic agent...

  16. Shaping of action potentials by type I and type II large-conductance Ca²+-activated K+ channels.

    Science.gov (United States)

    Jaffe, D B; Wang, B; Brenner, R

    2011-09-29

    The BK channel is a Ca(2+) and voltage-gated conductance responsible for shaping action potential waveforms in many types of neurons. Type II BK channels are differentiated from type I channels by their pharmacology and slow gating kinetics. The β4 accessory subunit confers type II properties on BK α subunits. Empirically derived properties of BK channels, with and without the β4 accessory subunit, were obtained using a heterologous expression system under physiological ionic conditions. These data were then used to study how BK channels alone (type I) and with the accessory β4 subunit (type II) modulate action potential properties in biophysical neuron models. Overall, the models support the hypothesis that it is the slower kinetics provided by the β4 subunit that endows the BK channel with type II properties, which leads to broadening of action potentials and, secondarily, to greater recruitment of SK channels reducing neuronal excitability. Two regions of parameter space distinguished type II and type I effects; one where the range of BK-activating Ca(2+) was high (>20 μM) and the other where BK-activating Ca(2+) was low (∼0.4-1.2 μM). The latter required an elevated BK channel density, possibly beyond a likely physiological range. BK-mediated sharpening of the spike waveform associated with the lack of the β4 subunit was sensitive to the properties of voltage-gated Ca(2+) channels due to electrogenic effects on spike duration. We also found that depending on Ca(2+) dynamics, type II BK channels may have the ability to contribute to the medium AHP, a property not generally ascribed to BK channels, influencing the frequency-current relationship. Finally, we show how the broadening of action potentials conferred by type II BK channels can also indirectly increase the recruitment of SK-type channels decreasing the excitability of the neuron.

  17. Action Potential Modulation in CA1 Pyramidal Neuron Axons Facilitates OLM Interneuron Activation in Recurrent Inhibitory Microcircuits of Rat Hippocampus

    OpenAIRE

    Sooyun Kim

    2014-01-01

    Oriens-lacunosum moleculare (O-LM) interneurons in the CA1 region of the hippocampus play a key role in feedback inhibition and in the control of network activity. However, how these cells are efficiently activated in the network remains unclear. To address this question, I performed recordings from CA1 pyramidal neuron axons, the presynaptic fibers that provide feedback innervation of these interneurons. Two forms of axonal action potential (AP) modulation were identified. First, repetitive ...

  18. Effects of nerve growth factor on the action potential duration and repolarizing currents in a rabbit model of myocardial infarction

    OpenAIRE

    Lan, Yun-Feng; Zhang, Jian-Cheng; Gao, Jin-Lao; Wang, Xue-Ping; Fang, Zhou; Fu, Yi-Cheng; Chen, Mei-Yan; Lin, Min; Xue, Qiao; Li, Yang

    2013-01-01

    Objectives To investigate the effect of nerve growth factor (NGF) on the action potential and potassium currents of non-infarcted myocardium in the myocardial infarcted rabbit model. Methods Rabbits with occlusion of the left anterior descending coronary artery were prepared and allowed to recover for eight weeks (healed myocardial infarction, HMI). During ligation surgery of the left coronary artery, a polyethylene tube was placed near the left stellate ganglion in the subcutis of the neck f...

  19. Morphological Characterization of the Action Potential Initiation Segment in GnRH Neuron Dendrites and Axons of Male Mice.

    Science.gov (United States)

    Herde, Michel K; Herbison, Allan E

    2015-11-01

    GnRH neurons are the final output neurons of the hypothalamic network controlling fertility in mammals. In the present study, we used ankyrin G immunohistochemistry and neurobiotin filling of live GnRH neurons in brain slices from GnRH-green fluorescent protein transgenic male mice to examine in detail the location of action potential initiation in GnRH neurons with somata residing at different locations in the basal forebrain. We found that the vast majority of GnRH neurons are bipolar in morphology, elaborating a thick (primary) and thinner (secondary) dendrite from opposite poles of the soma. In addition, an axon-like process arising predominantly from a proximal dendrite was observed in a subpopulation of GnRH neurons. Ankyrin G immunohistochemistry revealed the presence of a single action potential initiation zone ∼27 μm in length primarily in the secondary dendrite of GnRH neurons and located 30 to 140 μm distant from the cell soma, depending on the type of process and location of the cell body. In addition to dendrites, the GnRH neurons with cell bodies located close to hypothalamic circumventricular organs often elaborated ankyrin G-positive axon-like structures. Almost all GnRH neurons (>90%) had their action potential initiation site in a process that initially, or ultimately after a hairpin loop, was coursing in the direction of the median eminence. These studies indicate that action potentials are initiated in different dendritic and axonal compartments of the GnRH neuron in a manner that is dependent partly on the neuroanatomical location of the cell body.

  20. High-Bandwidth Atomic Force Microscopy Reveals A Mechanical spike Accompanying the Action Potential in mammalian Nerve Terminals

    Science.gov (United States)

    Salzberg, Brian M.

    2008-03-01

    Information transfer from neuron to neuron within nervous systems occurs when the action potential arrives at a nerve terminal and initiates the release of a chemical messenger (neurotransmitter). In the mammalian neurohypophysis (posterior pituitary), large and rapid changes in light scattering accompany secretion of transmitter-like neuropeptides. In the mouse, these intrinsic optical signals are intimately related to the arrival of the action potential (E-wave) and the release of arginine vasopressin and oxytocin (S-wave). We have used a high bandwidth (20 kHz) atomic force microscope (AFM) to demonstrate that these light scattering signals are associated with changes in nerve terminal volume, detected as nanometer-scale movements of a cantilever positioned on top of the neurohypophysis. The most rapid mechanical response, the ``spike'', has duration comparable to that of the action potential (˜2 ms) and probably reflects an increase in terminal volume due to H2O movement associated with Na^+-influx. Elementary calculations suggest that two H2O molecules accompanying each Na^+-ion could account for the ˜0.5-1.0 å increase in the diameter of each terminal during the action potential. Distinguishable from the mechanical ``spike'', a slower mechanical event, the ``dip'', represents a decrease in nerve terminal volume, depends upon Ca^2+-entry, as well as on intra-terminal Ca^2+-transients, and appears to monitor events associated with secretion. A simple hypothesis is that this ``dip'' reflects the extrusion of the dense core granule that comprises the secretory products. These dynamic high bandwidth AFM recordings are the first to monitor mechanical events in nervous systems and may provide novel insights into the mechanism(s) by which excitation is coupled to secretion at nerve terminals.

  1. 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...

  2. Complex Dynamic Thresholds and Generation of the Action Potentials in the Neural-Activity Model

    Science.gov (United States)

    Kirillov, S. Yu.; Nekorkin, V. I.

    2016-05-01

    This work is devoted to studying the processes of activation of the neurons whose excitation thresholds are not constant and vary in time (the so-called dynamic thresholds). The neuron dynamics is described by the FitzHugh-Nagumo model with nonlinear behavior of the recovery variable. The neuron response to the external pulsed activating action in the presence of a slowly varying synaptic current is studied within the framework of this model. The structure of the dynamic threshold is studied and its properties depending on the external-action parameters are established. It is found that the formation of the "folds" in the separatrix threshold manifold in the model phase space is a typical feature of the complex dynamic threshold. High neuron sensitivity to the action of the comparatively weak slow control signals is established. This explains the capability of the neurons to perform flexible tuning of their selective properties for detecting various external signals in sufficiently short times (of the order of duration of several spikes).

  3. 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 myocardial perfusion or the presence of an electromechanical decoupling agent (butanedione monoxime) during optical mapping. CONCLUSION: Acute loading of the left ventricle of the isolated rabbit heart decreased apparent epicardial conduction velocity and increased action potential duration by a load-dependent mechanism that may not involve stretch-activated channels.

  4. 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.

  5. Action potentials initiate in the axon initial segment and propagate through axon collaterals reliably in cerebellar Purkinje neurons.

    Science.gov (United States)

    Foust, Amanda; Popovic, Marko; Zecevic, Dejan; McCormick, David A

    2010-05-19

    Purkinje neurons are the output cells of the cerebellar cortex and generate spikes in two distinct modes, known as simple and complex spikes. Revealing the point of origin of these action potentials, and how they conduct into local axon collaterals, is important for understanding local and distal neuronal processing and communication. By using a recent improvement in voltage-sensitive dye imaging technique that provided exceptional spatial and temporal resolution, we were able to resolve the region of spike initiation as well as follow spike propagation into axon collaterals for each action potential initiated on single trials. All fast action potentials, for both simple and complex spikes, whether occurring spontaneously or in response to a somatic current pulse or synaptic input, initiated in the axon initial segment. At discharge frequencies of less than approximately 250 Hz, spikes propagated faithfully through the axon and axon collaterals, in a saltatory manner. Propagation failures were only observed for very high frequencies or for the spikelets associated with complex spikes. These results demonstrate that the axon initial segment is a critical decision point in Purkinje cell processing and that the properties of axon branch points are adjusted to maintain faithful transmission.

  6. Role of gap junction channel in the development of beat-to-beat action potential repolarization variability and arrhythmias.

    Science.gov (United States)

    Magyar, Janos; Banyasz, Tamas; Szentandrassy, Norbert; Kistamas, Kornel; Nanasi, Peter P; Satin, Jonathan

    2015-01-01

    The short-term beat-to-beat variability of cardiac action potential duration (SBVR) occurs as a random alteration of the ventricular repolarization duration. SBVR has been suggested to be more predictive of the development of lethal arrhythmias than the action potential prolongation or QT prolongation of ECG alone. The mechanism underlying SBVR is not completely understood but it is known that SBVR depends on stochastic ion channel gating, intracellular calcium handling and intercellular coupling. Coupling of single cardiomyocytes significantly decreases the beat-to-beat changes in action potential duration (APD) due to the electrotonic current flow between neighboring cells. The magnitude of this electrotonic current depends on the intercellular gap junction resistance. Reduced gap junction resistance causes greater electrotonic current flow between cells, and reduces SBVR. Myocardial ischaemia (MI) is known to affect gap junction channel protein expression and function. MI increases gap junction resistance that leads to slow conduction, APD and refractory period dispersion, and an increase in SBVR. Ultimately, development of reentry arrhythmias and fibrillation are associated post-MI. Antiarrhythmic drugs have proarrhythmic side effects requiring alternative approaches. A novel idea is to target gap junction channels. Specifically, the use of gap junction channel enhancers and inhibitors may help to reveal the precise role of gap junctions in the development of arrhythmias. Since cell-to-cell coupling is represented in SBVR, this parameter can be used to monitor the degree of coupling of myocardium.

  7. Amplitude of sensory nerve action potential in early stage diabetic peripheral neuropathy:an analysis of 500 cases

    Institute of Scientific and Technical Information of China (English)

    Yunqian Zhang; Jintao Li; Tingjuan Wang; Jianlin Wang

    2014-01-01

    Early diagnosis of diabetic peripheral neuropathy is important for the successful treatment of diabetes mellitus. In the present study, we recruited 500 diabetic patients from the Fourth Afifl-iated Hospital of Kunming Medical University in China from June 2008 to September 2013: 221 cases showed symptoms of peripheral neuropathy (symptomatic group) and 279 cases had no symptoms of peripheral impairment (asymptomatic group). One hundred healthy control sub-jects were also recruited. Nerve conduction studies revealed that distal motor latency was longer, sensory nerve conduction velocity was slower, and sensory nerve action potential and amplitude of compound muscle action potential were signiifcantly lower in the median, ulnar, posterior tibial and common peroneal nerve in the diabetic groups compared with control subjects. More-over, the alterations were more obvious in patients with symptoms of peripheral neuropathy. Of the 500 diabetic patients, neural conduction abnormalities were detected in 358 cases (71.6%), among which impairment of the common peroneal nerve was most prominent. Sensory nerve abnormality was more obvious than motor nerve abnormality in the diabetic groups. The ampli-tude of sensory nerve action potential was the most sensitive measure of peripheral neuropathy. Our results reveal that varying degrees of nerve conduction changes are present in the early, as-ymptomatic stage of diabetic peripheral neuropathy.

  8. Amplitude of sensory nerve action potential in early stage diabetic peripheral neuropathy: an analysis of 500 cases.

    Science.gov (United States)

    Zhang, Yunqian; Li, Jintao; Wang, Tingjuan; Wang, Jianlin

    2014-07-15

    Early diagnosis of diabetic peripheral neuropathy is important for the successful treatment of diabetes mellitus. In the present study, we recruited 500 diabetic patients from the Fourth Affiliated Hospital of Kunming Medical University in China from June 2008 to September 2013: 221 cases showed symptoms of peripheral neuropathy (symptomatic group) and 279 cases had no symptoms of peripheral impairment (asymptomatic group). One hundred healthy control subjects were also recruited. Nerve conduction studies revealed that distal motor latency was longer, sensory nerve conduction velocity was slower, and sensory nerve action potential and amplitude of compound muscle action potential were significantly lower in the median, ulnar, posterior tibial and common peroneal nerve in the diabetic groups compared with control subjects. Moreover, the alterations were more obvious in patients with symptoms of peripheral neuropathy. Of the 500 diabetic patients, neural conduction abnormalities were detected in 358 cases (71.6%), among which impairment of the common peroneal nerve was most prominent. Sensory nerve abnormality was more obvious than motor nerve abnormality in the diabetic groups. The amplitude of sensory nerve action potential was the most sensitive measure of peripheral neuropathy. Our results reveal that varying degrees of nerve conduction changes are present in the early, asymptomatic stage of diabetic peripheral neuropathy.

  9. 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

    2007-01-01

    Background and purpose: Torsade de pointes (TdP) can be induced by a reduction in cardiac repolarizing capacity. The aim of this study was to assess whether I Ks blockade or enhancement of I Na could potentiate TdP induced by I Kr blockade and to investigate whether short-term variability (STV) or triangulation of action potentials preceded TdP. Experimental approach: Experiments were performed in open-chest, pentobarbital-anaesthetized, α1-adrenoceptor-stimulated, male New Zealand White rabbits, which received three consecutive i.v. infusions of either the I Kr blocker E-4031 (1, 3 and 10 nmol kg−1 min−1), the I Ks 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 I Na 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. Key results: 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. Conclusions and implications: Giving modulators of ion channels in combination substantially increased TdP but, in this model, neither STV nor triangulation of action potentials could predict TdP. PMID:17965747

  10. Adaptation decision-making in the Nordic Countries: assessing the potential for joint action

    DEFF Research Database (Denmark)

    Juhola, Sirkku; Goodsite, Michael Evan; Davis, Marion

    2014-01-01

    on the issue. This paper explores the potential for Nordic cooperation on adaptation; specifically, for the development of a regional adaptation strategy. In particular, it addresses two questions (1) What is the current state of adaptation in the Nordic countries? and (2) What are the potential benefits...

  11. Potential for bias in the context of neuroethics. Commentary on "Neuroscience, neuropolitics and neuroethics: the complex case of crime, deception and fMRI".

    Science.gov (United States)

    Bird, Stephanie J

    2012-09-01

    Neuroscience research, like all science, is vulnerable to the influence of extraneous values in the practice of research, whether in research design or the selection, analysis and interpretation of data. This is particularly problematic for research into the biological mechanisms that underlie behavior, and especially the neurobiological underpinnings of moral development and ethical reasoning, decision-making and behavior, and the other elements of what is often called the neuroscience of ethics. The problem arises because neuroscientists, like most everyone, bring to their work assumptions, preconceptions and values and other sources of potentially inappropriate bias of which they may be unaware. It is important that the training of neuroscientists, and research practice itself, include open and in-depth discussion and examination of the assumptions that underlie research. Further, policy makers, journalists, and the general public, that is, the consumers of neuroscience research findings (and by extension, neurotechnologies) should be made aware of the limitations as well as the strengths of the science, the evolving nature of scientific understanding, and the often invisible values inherent in science.

  12. Antidiabetic Drugs: Mechanisms of Action and Potential Outcomes on Cellular Metabolism.

    Science.gov (United States)

    Meneses, Maria J; Silva, Branca M; Sousa, Mário; Sá, Rosália; Oliveira, Pedro F; Alves, Marco G

    2015-01-01

    Diabetes mellitus (DM) is one of the most prevalent chronic diseases and has been a leading cause of death in the last decades. Thus, methods to detect, prevent or delay this disease and its co-morbidities have long been a matter of discussion. Nowadays, DM patients, particularly those suffering with type 2 DM, are advised to alter their diet and physical exercise regimens and then proceed progressively from monotherapy, dual therapy, and multi-agent therapy to insulin administration, as the disease becomes more severe. Although progresses have been made, the pursuit for the "perfect" antidiabetic drug still continues. The complexity of DM and its impact on whole body homeodynamics are two of the main reasons why there is not yet such a drug. Moreover, the molecular mechanisms by which DM can be controlled are still under an intense debate. As the associated risks, disadvantages, side effects and mechanisms of action vary from drug to drug, the choice of the most suitable therapy needs to be thoroughly investigated. Herein we propose to discuss the different classes of antidiabetic drugs available, their applications and mechanisms of action, particularly those of the newer and/or most widely prescribed classes. A special emphasis will be made on their effects on cellular metabolism, since these drugs affect those pathways in several cellular systems and organs, promoting metabolic alterations responsible for either deleterious or beneficial effects. This is a crucial property that needs to be carefully investigated when prescribing an antidiabetic.

  13. Corticospinal neurons in macaque ventral premotor cortex with mirror properties: a potential mechanism for action suppression?

    Science.gov (United States)

    Kraskov, Alexander; Dancause, Numa; Quallo, Marsha M; Shepherd, Samantha; Lemon, Roger N

    2009-12-24

    The discovery of "mirror neurons" in area F5 of the ventral premotor cortex has prompted many theories as to their possible function. However, the identity of mirror neurons remains unknown. Here, we investigated whether identified pyramidal tract neurons (PTNs) in area F5 of two adult macaques exhibited "mirror-like" activity. About half of the 64 PTNs tested showed significant modulation of their activity while monkeys observed precision grip of an object carried out by an experimenter, with somewhat fewer showing modulation during precision grip without an object or grasping concealed from the monkey. Therefore, mirror-like activity can be transmitted directly to the spinal cord via PTNs. A novel finding is that many PTNs (17/64) showed complete suppression of discharge during action observation, while firing actively when the monkey grasped food rewards. We speculate that this suppression of PTN discharge might be involved in the inhibition of self-movement during action observation. 2009 Elsevier Inc. All rights reserved.

  14. 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

  15. Modulatory action of acetylcholine on the Na+-dependent action potentials in Kenyon cells isolated from the mushroom body of the cricket brain.

    Science.gov (United States)

    Terazima, E; Yoshino, M

    2010-12-01

    Kenyon cells, intrinsic neurons of the insect mushroom body, have been assumed to be a site of conditioning stimulus (CS) and unconditioned stimulus (US) association in olfactory learning and memory. Acetylcholine (ACh) has been implicated to be a neurotransmitter mediating CS reception in Kenyon cells, causing rapid membrane depolarization via nicotinic ACh receptors. However, the long-term effects of ACh on the membrane excitability of Kenyon cells are not fully understood. In this study, we examined the effects of ACh on Na(+) dependent action potentials (Na(+) spikes) elicited by depolarizing current injection and on net membrane currents under the voltage clamp condition in Kenyon cells isolated from the mushroom body of the cricket Gryllus bimaculatus. Current-clamp studies using amphotericin B perforated-patch recordings showed that freshly dispersed cricket Kenyon cells could produce repetitive Na(+) spikes in response to prolonged depolarizing current injection. Bath application of ACh increased both the instantaneous frequency and the amplitudes of Na(+) spikes. This excitatory action of ACh on Kenyon cells is attenuated by the pre-treatment of the cells with the muscarinic receptor antagonists, atropine and scopolamine, but not by the nicotinic receptor antagonist mecamylamine. Voltage-clamp studies further showed that bath application of ACh caused an increase in net inward currents that are sensitive to TTX, whereas outward currents were decreased by this treatment. These results indicate that in order to mediate CS, ACh may modulate the firing properties of Na(+) spikes of Kenyon cells through muscarinic receptor activation, thus increasing Na conductance and decreasing K conductance.

  16. Methanol extract of Tephrosia vogelii leaves potentiates the contractile action of acetylcholine on isolated rabbit jejunum

    Directory of Open Access Journals (Sweden)

    Tavershima Dzenda

    2015-09-01

    Conclusions: The findings demonstrate that methanol extract of Tephrosia vogelii leaves potentiates the contractile effect of ACh on intestinal smooth muscle, supporting the traditional claim that the plant is purgative.

  17. Waveform Similarity Analysis: A Simple Template Comparing Approach for Detecting and Quantifying Noisy Evoked Compound Action Potentials.

    Science.gov (United States)

    Potas, Jason Robert; de Castro, Newton Gonçalves; Maddess, Ted; de Souza, Marcio Nogueira

    2015-01-01

    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 studying evoked compound

  18. Cardiovascular pleiotropic actions of DPP-4 inhibitors: a step at the cutting edge in understanding their additional therapeutic potentials.

    Science.gov (United States)

    Balakumar, Pitchai; Dhanaraj, Sokkalingam A

    2013-09-01

    Dipeptidyl peptidase 4 (DPP-4) is a serine protease enzyme expressed widely in many tissues, including the cardiovascular system. The incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released from the small intestine into the vasculature during a meal, and these incretins have a potential to release insulin from pancreatic beta cells of islets of Langerhans, affording a glucose-lowering action. However, both incretins are hurriedly degraded by the DPP-4. Inhibitors of DPP-4, therefore, enhance the bioavailability of GLP-1 and GIP, and thus have been approved for better glycemic management in patients afflicted with type 2 diabetes mellitus (T2DM). Five different DPP-4 inhibitors, often called as 'gliptins', namely sitagliptin, vildagliptin, saxagliptin, linagliptin and alogliptin have been approved hitherto for clinical use. These drugs are used along with diet and exercise to lower blood sugar in diabetic subjects. T2DM is intricately related with an increased risk of cardiovascular disease. Growing body of evidence suggests that gliptins, in addition to their persuasive anti-diabetic action, have a beneficial pleiotropic action on the heart and vessels. In view of the fact of cardiovascular disease susceptibility of patients afflicted with T2DM, gliptins might offer additional therapeutic benefits in treating diabetic cardiovascular complications. Exploring further the cardiovascular pleiotropic potentials of gliptins might open a panorama in impeccably employing these agents for the dual management of T2DM and T2DM-associated perilous cardiovascular complications. This review will shed lights on the newly identified beneficial pleiotropic actions of gliptins on the cardiovascular system.

  19. Computational modeling of voltage-gated Ca channels inhibition: identification of different effects on uterine and cardiac action potentials

    Directory of Open Access Journals (Sweden)

    Wing Chiu eTong

    2014-10-01

    Full Text Available The uterus and heart share the important physiological feature whereby contractile activation of the muscle tissue is regulated by the generation of periodic, spontaneous electrical action potentials (APs. Preterm birth arising from premature uterine contractions is a major complication of pregnancy and there remains a need to pursue avenues of research that facilitate the use of drugs, tocolytics, to limit these inappropriate contractions without deleterious actions on cardiac electrical excitation. A novel approach is to make use of mathematical models of uterine and cardiac APs, which incorporate many ionic currents contributing to the AP forms, and test the cell-specific responses to interventions. We have used three such models – of uterine smooth muscle cells (USMC, cardiac sinoatrial node cells (SAN and ventricular cells – to investigate the relative effects of reducing two important voltage-gated Ca currents – the L-type (ICaL and T-type (ICaT Ca currents. Reduction of ICaL (10% alone, or ICaT (40% alone, blunted USMC APs with little effect on ventricular APs and only mild effects on SAN activity. Larger reductions in either current further attenuated the USMC APs but with also greater effects on SAN APs. Encouragingly, a combination of ICaL and ICaT reduction did blunt USMC APs as intended with little detriment to APs of either cardiac cell type. Subsequent overlapping maps of ICaL and ICaT inhibition profiles from each model revealed a range of combined reductions of ICaL and ICaT over which an appreciable diminution of USMC APs could be achieved with no deleterious action on cardiac SAN or ventricular APs. This novel approach illustrates the potential for computational biology to inform us of possible uterine and cardiac cell-specific mechanisms. Incorporating such computational approaches in future studies directed at designing new, or repurposing existing, tocolytics will be beneficial for establishing a desired uterine

  20. Bursting regimes in a reaction-diffusion system with action potential-dependent equilibrium.

    Directory of Open Access Journals (Sweden)

    Stephen R Meier

    Full Text Available The equilibrium Nernst potential plays a critical role in neural cell dynamics. A common approximation used in studying electrical dynamics of excitable cells is that the ionic concentrations inside and outside the cell membranes act as charge reservoirs and remain effectively constant during excitation events. Research into brain electrical activity suggests that relaxing this assumption may provide a better understanding of normal and pathophysiological functioning of the brain. In this paper we explore time-dependent ionic concentrations by allowing the ion-specific Nernst potentials to vary with developing transmembrane potential. As a specific implementation, we incorporate the potential-dependent Nernst shift into a one-dimensional Morris-Lecar reaction-diffusion model. Our main findings result from a region in parameter space where self-sustaining oscillations occur without external forcing. Studying the system close to the bifurcation boundary, we explore the vulnerability of the system with respect to external stimulations which disrupt these oscillations and send the system to a stable equilibrium. We also present results for an extended, one-dimensional cable of excitable tissue tuned to this parameter regime and stimulated, giving rise to complex spatiotemporal pattern formation. Potential applications to the emergence of neuronal bursting in similar two-variable systems and to pathophysiological seizure-like activity are discussed.

  1. Ionic mechanisms in the generation of subthreshold oscillations and action potential clustering in entorhinal layer II stellate neurons.

    Science.gov (United States)

    Fransén, Erik; Alonso, Angel A; Dickson, Clayton T; Magistretti, Jacopo; Hasselmo, Michael E

    2004-01-01

    A multicompartmental biophysical model of entorhinal cortex layer II stellate cells was developed to analyze the ionic basis of physiological properties, such as subthreshold membrane potential oscillations, action potential clustering, and the medium afterhyperpolarization. In particular, the simulation illustrates the interaction of the persistent sodium current (I(Nap)) and the hyperpolarization activated inward current (Ih) in the generation of subthreshold membrane potential oscillations. The potential role of Ih in contributing to the medium hyperpolarization (mAHP) and rebound spiking was studied. The role of Ih and the slow calcium-activated potassium current Ikappa(AHP) in action potential clustering was also studied. Representations of Ih and I(Nap) were developed with parameters based on voltage-clamp data from whole-cell patch and single channel recordings of stellate cells (Dickson et al., J Neurophysiol 83:2562-2579, 2000; Magistretti and Alonso, J Gen Physiol 114:491-509, 1999; Magistretti et al., J Physiol 521:629-636, 1999a; J Neurosci 19:7334-7341, 1999b). These currents interacted to generate robust subthreshold membrane potentials with amplitude and frequency corresponding to data observed in the whole cell patch recordings. The model was also able to account for effects of pharmacological manipulations, including blockade of Ih with ZD7288, partial blockade with cesium, and the influence of barium on oscillations. In a model with a wider range of currents, the transition from oscillations to single spiking, to spike clustering, and finally tonic firing could be replicated. In agreement with experiment, blockade of calcium channels in the model strongly reduced clustering. In the voltage interval during which no data are available, the model predicts that the slow component of Ih does not follow the fast component down to very short time constants. The model also predicts that the fast component of Ih is responsible for the involvement in the

  2. Exercise-induced expression of cardiac ATP-sensitive potassium channels promotes action potential shortening and energy conservation

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    Zingman, Leonid V.; Zhu, Zhiyong; Sierra, Ana; Stepniak, Elizabeth; Burnett, Colin M-L.; Maksymov, Gennadiy; Anderson, Mark E.; Coetzee, William A.; Hodgson-Zingman, Denice M.

    2011-01-01

    Physical activity is one of the most important determinants of cardiac function. The ability of the heart to increase delivery of oxygen and metabolic fuels relies on an array of adaptive responses necessary to match bodily demand while avoiding exhaustion of cardiac resources. The ATP-sensitive potassium (KATP) channel has the unique ability to adjust cardiac membrane excitability in accordance with ATP and ADP levels, and up-regulation of its expression that occurs in response to exercise could represent a critical element of this adaption. However, the mechanism by which KATP channel expression changes result in a beneficial effect on cardiac excitability and function remains to be established. Here, we demonstrate that an exercise-induced rise in KATP channel expression enhanced the rate and magnitude of action potential shortening in response to heart rate acceleration. This adaptation in membrane excitability promoted significant reduction in cardiac energy consumption under escalating workloads. Genetic disruption of normal KATP channel pore function abolished the exercise-related changes in action potential duration adjustment and caused increased cardiac energy consumption. Thus, an expression-driven enhancement in the KATP channel-dependent membrane response to alterations in cardiac workload represents a previously unrecognized mechanism for adaptation to physical activity and a potential target for cardioprotection. PMID:21439969

  3. The spatio-temporal characteristics of action potential initiation in layer 5 pyramidal neurons: a voltage imaging study.

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    Popovic, Marko A; Foust, Amanda J; McCormick, David A; Zecevic, Dejan

    2011-09-01

    The spatial pattern of Na(+) channel clustering in the axon initial segment (AIS) plays a critical role in tuning neuronal computations, and changes in Na(+) channel distribution have been shown to mediate novel forms of neuronal plasticity in the axon. However, immunocytochemical data on channel distribution may not directly predict spatio-temporal characteristics of action potential initiation, and prior electrophysiological measures are either indirect (extracellular) or lack sufficient spatial resolution (intracellular) to directly characterize the spike trigger zone (TZ). We took advantage of a critical methodological improvement in the high sensitivity membrane potential imaging (V(m) imaging) technique to directly determine the location and length of the spike TZ as defined in functional terms. The results show that in mature axons of mouse cortical layer 5 pyramidal cells, action potentials initiate in a region ∼20 μm in length centred between 20 and 40 μm from the soma. From this region, the AP depolarizing wave invades initial nodes of Ranvier within a fraction of a millisecond and propagates in a saltatory fashion into axonal collaterals without failure at all physiologically relevant frequencies. We further demonstrate that, in contrast to the saltatory conduction in mature axons, AP propagation is non-saltatory (monotonic) in immature axons prior to myelination.

  4. 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.

  5. EFFECTS OF DESENSITIZATION AND REBOUND TO ADENOSINE ON ACTION POTENTIAL AND CONTRACTILITY IN ATRIAL CELLS IN GUINEA-PIGS

    Institute of Scientific and Technical Information of China (English)

    张凤杰; 臧伟进; 于晓江; 胡浩; 张春虹; 孙强; 吕军

    2002-01-01

    Objective To investigate the effects of desensitization and rebound to adenosine(Ado) on action potential duration(APD) and contractility in guinea-pig atrial cells. Methods Electrical activity was recorded using standard intracellular microelectrode technique and contractility was recorded using. We studied the effects of adenosine on the action potential and desensitization of contractility and rebound of contractility. Results The results showed that action potential duration were shortened by 1,10,100μmol*L-1Ado, the ratio of shortened APD was (9.58±1.40)%,(13.80±2.26)%,(24.80±3.19)%, respectively. 1μmol*L-1Ado had no desensitization (P>0.05), but the time of desensitization of 10μmol*L-1 Ado and 100μmol*L-1 Ado was 1 minute(P<0.05) and 5 minutes(P<0.05), respectively. The desensitization of contractility of 10*!μmol*L-1 Ado was obvious in atrial cells, the decrease of contractility of 10*!μmol*L-1 Ado was obvious in atrial cells, the decrease of contractility was changed from (31.4±16.04)%(2 minutes) to (50.60±15.87)% (4 minutes), compared with control. After washing out Ado, contractility was shown to rebound, the ratio of increase of contractility by 1,10,100μmol*L-1 Ado was (12.38±7.50)%,(19.00±8.14)% and (27.60±13.44)%, respectively. Conclusion Ado can abbreviate APD in atrial cells. The desensitization of Ado on APD is characterized by concentration-dependent and time-dependent in atrial cells, and the desensitization of contractility of Ado is obvious and contractility was shown to rebound after washing out Ado.

  6. Recovery time of motor evoked potentials following lengthening and shortening muscle action in the tibialis anterior

    NARCIS (Netherlands)

    Tallent, J.; Goodall, S.; Hortobagyi, T.; Gibson, A. St Clair; French, D. N.; Howatson, G.

    2012-01-01

    Motor evoked potentials (MEP) at rest remain facilitated following an isometric muscle contraction. Because the pre-synaptic and post-synaptic control of shortening (SHO) and lengthening (LEN) contractions differs, the possibility exists that the recovery of the MEP is also task specific. The time c

  7. Immunomodulatory effects of fluoxetine: A new potential pharmacological action for a classic antidepressant drug?

    Science.gov (United States)

    Di Rosso, María Emilia; Palumbo, María Laura; Genaro, Ana María

    2016-07-01

    Selective serotonin reuptake inhibitors are frequently used antidepressants. In particular, fluoxetine is usually chosen for the treatment of the symptoms of depression, obsessive-compulsive, panic attack and bulimia nervosa. Antidepressant therapy has been associated with immune dysfunction. However, there is contradictory evidence about the effect of fluoxetine on the immune system. Experimental findings indicate that lymphocytes express the serotonin transporter. Moreover it has been shown that fluoxetine is able to modulate the immune function through a serotonin-dependent pathway and through a novel independent mechanism. In addition, several studies have shown that fluoxetine can alter tumor cell viability. Thus, it was recently demonstrated in vivo that chronic fluoxetine treatment inhibits tumor growth by increasing antitumor T-cell activity. Here we briefly review some of the literature referring to how fluoxetine is able to modify, for better or worse, the functionality of the immune system. These results of our analysis point to the relevance of the novel pharmacological action of this drug as an immunomodulator helping to treat several pathologies in which immune deficiency and/or deregulation is present.

  8. Potential Mechanism of Action of meso-Dihydroguaiaretic Acid on Mycobacterium tuberculosis H37Rv

    Directory of Open Access Journals (Sweden)

    Aldo F. Clemente-Soto

    2014-12-01

    Full Text Available The isolation and characterization of the lignan meso-dihydroguaiaretic acid (MDGA from Larrea tridentata and its activity against Mycobacterial tuberculosis has been demonstrated, but no information regarding its mechanism of action has been documented. Therefore, in this study we carry out the gene expression from total RNA obtained from M. tuberculosis H37Rv treated with MDGA using microarray technology, which was validated by quantitative real time polymerase chain reaction. Results showed that the alpha subunit of coenzyme A transferase of M. tuberculosis H37Rv is present in both geraniol and 1-and 2-methylnaphthalene degradation pathways, which are targeted by MDGA. This assumption was supported by molecular docking which showed stable interaction between MDGA with the active site of the enzyme. We propose that inhibition of coenzyme A transferase of M. tuberculosis H37Rv results in the accumulation of geraniol and 1-and 2-methylnaphtalene inside bacteria, causing membrane destabilization and death of the pathogen. The natural product MDGA is thus an attractive template to develop new anti-tuberculosis drugs, because its target is different from those of known anti-tubercular agents.

  9. Potential mechanism of action of meso-dihydroguaiaretic acid on Mycobacterium tuberculosis H37Rv.

    Science.gov (United States)

    Clemente-Soto, Aldo F; Balderas-Rentería, Isaías; Rivera, Gildardo; Segura-Cabrera, Aldo; Garza-González, Elvira; del Rayo Camacho-Corona, María

    2014-12-02

    The isolation and characterization of the lignan meso-dihydroguaiaretic acid (MDGA) from Larrea tridentata and its activity against Mycobacterial tuberculosis has been demonstrated, but no information regarding its mechanism of action has been documented. Therefore, in this study we carry out the gene expression from total RNA obtained from M. tuberculosis H37Rv treated with MDGA using microarray technology, which was validated by quantitative real time polymerase chain reaction. Results showed that the alpha subunit of coenzyme A transferase of M. tuberculosis H37Rv is present in both geraniol and 1-and 2-methylnaphthalene degradation pathways, which are targeted by MDGA. This assumption was supported by molecular docking which showed stable interaction between MDGA with the active site of the enzyme. We propose that inhibition of coenzyme A transferase of M. tuberculosis H37Rv results in the accumulation of geraniol and 1-and 2-methylnaphtalene inside bacteria, causing membrane destabilization and death of the pathogen. The natural product MDGA is thus an attractive template to develop new anti-tuberculosis drugs, because its target is different from those of known anti-tubercular agents.

  10. A major role for calcium-dependent potassium current in action potential repolarization in adrenal chromaffin cells.

    Science.gov (United States)

    Pancrazio, J J; Johnson, P A; Lynch, C

    1994-12-30

    To determine the extent which Ca dependent K current (IKCa) contributes during an action potential (AP), bovine chromaffin cells were voltage-clamped using a pre-recorded AP as the command voltage waveform. Based on (1) differential sensitivity of IKCa and Ca-independent K current (IK) to tetraethylammonium; (2) measurements of AP currents under conditions where Ca activation of IKCa had been abolished; and (3) blockade by charybdotoxin, IKCa comprised 70-90% of the outward K current during AP repolarization. In addition, observations are made concerning the form of AP-evoked Ca current.

  11. 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.

  12. Review article: potential mechanisms of action of rifaximin in the management of irritable bowel syndrome with diarrhoea.

    Science.gov (United States)

    Pimentel, M

    2016-01-01

    The role of gut microbiota in the pathophysiology of irritable bowel syndrome (IBS) is supported by various lines of evidence, including differences in mucosal and faecal microbiota between patients with IBS and healthy individuals, development of post-infectious IBS, and the efficacy of some probiotics and nonsystemic antibiotics (e.g. rifaximin). To review the literature regarding the role of rifaximin in IBS and its potential mechanism(s) of action. A literature search was conducted using the terms 'rifaximin', 'irritable bowel syndrome' and 'mechanism of action'. Rifaximin was approved in 2015 for the treatment of IBS with diarrhoea. In contrast to other currently available IBS therapies that require daily administration to maintain efficacy, 2-week rifaximin treatment achieved symptom improvement that persisted ≥12 weeks post-treatment. The mechanisms of action of rifaximin, therefore, may extend beyond direct bactericidal effects. Data suggest that rifaximin may decrease host proinflammatory responses to bacterial products in patients with IBS. In some cases, small intestinal bacterial overgrowth (SIBO) may play a role in the clinical symptoms of IBS. Because of the high level of solubility of rifaximin in the small intestine, rifaximin may reset microbial diversity in this environment. Consistent with this hypothesis, rifaximin has antibiotic efficacy against isolates derived from patients with SIBO. Resetting microbial diversity via rifaximin use may lead to a decrease in bacterial fermentation and a reduction in the clinical symptoms of IBS. © 2015 John Wiley & Sons Ltd.

  13. Navy Ship Maintenance: Action Needed to Maximize New Contracting Strategys Potential Benefits

    Science.gov (United States)

    2016-11-01

    and to capitalize on anticipated benefits, and (3) how the strategy will potentially affect the Navy’s ship repair industrial base. GAO analyzed...MAC-MO contracting strategy, (2) process changes the Navy has taken to address any challenges and to capitalize on anticipated benefits, and (3) how...Regulation (FAR) provisions and MSMO contracts. To assess process changes the Navy has taken to address challenges and to capitalize on intended

  14. The mechanism of action of two bradykinin-potentiating peptides on isolated smooth muscle.

    Science.gov (United States)

    Ufkes, J G; Aarsen, P N; van der Meer, C

    1977-07-15

    Bradykinin-induced contractions in the guinea-pig ileum were potentiated by the peptides A-VI-5 (Val-Glu-Ser-Ser-Lys) and BPP5a (Pyr-Lys-Trp-Ala-Pro), while the contractions induced by other agonists were not affected. Neither peptide added alone caused any response. Previous addition of the peptides shortened the latent period following the addition of bradykinin to a value corresponding to the contraction height with an equivalent dose of bradykinin added alone. Bradykinin in contact with a piece of ileum was inactivated at a relatively slow rate. This inactivation was not inhibited by either A-VI-5 or BPP5a in doses causing potentiation. Suppression of the cholinergic activity by cooling, atropine, morphine or tetrodotoxin did not influence the potentiating activity. Addition of the peptides at the moment a submaximal contraction due to bradykinin had been fully established, increased the contraction height within seconds. The two peptides caused a parallel shift to the left of the dose-effect curve of bradykinin, whereas the maximum bradykinin effect remained unchanged. It is concluded that sensitization of bradykinin receptors due to an increased affinity of the receptor for bradykinin is the hypothesis which best fits the experimental findings.

  15. Genotoxic and cytotoxic action potential of Terminalia citrina, a medicinal plant of ethnopharmacological significance

    Science.gov (United States)

    Akhtar, Muhammad Furqan; Saleem, Ammara; Sharif, Ali; Akhtar, Bushra; Nasim, Maaz Bin; Peerzada, Sohaib; Raza, Moosa; Ijaz, Hira; Ahmed, Shoaib; Shabbir, Maryam; Ali, Sajid; Akbar, Zeeshan; Ul Hassan, Syed Saeed

    2016-01-01

    Most herbal medicines utilized in complementary and alternative medicine lack safety evaluation setting our lives under unwarranted risks. Present study comprised of genotoxic and cytotoxic appraisal of Terminalia citrina fruits which are used as a folklore medicine for treatment of various ailments. Aqueous and ethanolic extracts of T. citrina fruit extracts were evaluated for the presence of different phytochemicals. Genotoxic potential of both the extract of T. citrina was assessed through Ames reverse mutagenicity assay in Salmonella TA 100 and 102 strains. Cytotoxic potential of T. citrina was determined in baby hamster kidney cell line (BHK-21). Statistical analysis was carried out by ANOVA following post hoc test. Phytochemical analysis showed the presence of alkaloids, carbohydrates, phenolic compounds, tannins, catechins and saponins. It was revealed that both the extracts of T. citrina exhibited significant mutagenicity in tester strains. Ethanolic extract showed higher mutagenicity in TA 100 strain, whereas aqueous extract of T. citrina exhibited higher mutagenicity in TA 102 strain than TA 100. Both the extracts of T. citrina showed dose-dependent mutagenicity. Fifty percent cell viability was exhibited by 260 and 545 µg/mL of ethanolic and aqueous extracts respectively. This study concludes that the ethanolic and aqueous fruit extracts of T. citrina may not be safe owing to their mutagenic and cytotoxic potential and it necessitates further investigation regarding its safety evaluation. PMID:28096789

  16. Effect of cardiac glycosides on action potential characteristics and contractility in cat ventricular myocytes: role of calcium overload.

    Science.gov (United States)

    Ruch, Stuart R; Nishio, Manabu; Wasserstrom, J Andrew

    2003-10-01

    There is increasing evidence that cardiac glycosides act through mechanisms distinct from inhibition of the sodium pump but which may contribute to their cardiac actions. To more fully define differences between agents indicative of multiple sites of action, we studied changes in contractility and action potential (AP) configuration in cat ventricular myocytes produced by six cardiac glycosides (ouabain, ouabagenin, dihydroouabain, actodigin, digoxin, and resibufogenin). AP shortening was observed only with ouabain and actodigin. There was extensive inotropic variability between agents, with some giving full inotropic effects before automaticity occurred whereas others produced minimal inotropy before toxicity. AP shortening was not a result of alterations in calcium current or the inward rectifier potassium current, but correlated with an increase in steady-state outward current (Iss), which was sensitive to KB-R7943, a Na+-Ca2+ exchange (NCX) inhibitor. Interestingly, Iss was observed following exposure to ouabain and dihydroouabain, suggesting that an additional mechanism is operative with dihydroouabain that prevents AP shortening. Further investigation into differences in inotropy between ouabagenin, dihydroouabain and ouabain revealed almost identical responses under AP voltage clamp. Thus all agents appear to act on the sodium pump and thereby secondarily increase the outward reverse mode NCX current, but the extent of AP duration shortening and positive inotropy elicited by each agent is limited by development of their toxic actions. The quantitative differences between cardiac glycosides suggest that mechanisms independent of sodium pump inhibition may result from an altered threshold for calcium overload possibly involving direct or indirect effects on calcium release from the sarcoplasmic reticulum.

  17. Fast calcium and voltage-sensitive dye imaging in enteric neurones reveal calcium peaks associated with single action potential discharge.

    Science.gov (United States)

    Michel, K; Michaelis, M; Mazzuoli, G; Mueller, K; Vanden Berghe, P; Schemann, M

    2011-12-15

    Slow changes in [Ca(2+)](i) reflect increased neuronal activity. Our study demonstrates that single-trial fast [Ca(2+)](i) imaging (≥200 Hz sampling rate) revealed peaks each of which are associated with single spike discharge recorded by consecutive voltage-sensitive dye (VSD) imaging in enteric neurones and nerve fibres. Fast [Ca(2+)](i) imaging also revealed subthreshold fast excitatory postsynaptic potentials. Nicotine-evoked [Ca(2+)](i) peaks were reduced by -conotoxin and blocked by ruthenium red or tetrodotoxin. Fast [Ca(2+)](i) imaging can be used to directly record single action potentials in enteric neurones. [Ca(2+)](i) peaks required opening of voltage-gated sodium and calcium channels as well as Ca(2+) release from intracellular stores.

  18. The growth cones of Aplysia sensory neurons: Modulation by serotonin of action potential duration and single potassium channel currents.

    Science.gov (United States)

    Belardetti, F; Schacher, S; Kandel, E R; Siegelbaum, S A

    1986-09-01

    Serotonin (5-HT) closes a specific K channel ("S") in the cell body of Aplysia sensory neurons, resulting in a slow excitatory postsynaptic potential and spike broadening. To determine whether the S channel is present and can be modulated in processes of the neuron other than the cell body, we studied the effects of 5-HT on growth cones of sensory neurons in culture by using the patch-clamp technique. Simultaneous application of 5-HT to the cell body and to the growth cones of sensory neurons produced, in both, a slow depolarization of approximately 5 mV. Also, 5-HT produced a lengthening of the duration of action potential in the growth cone and cell body by 20-30%. Similar effects were observed in isolated growth cones that had been severed from the rest of the neuron, implying that the growth cones contain all the molecular components (i.e., receptors, channels, cAMP cascade) necessary for 5-HT action. Cell-attached patch-clamp recordings demonstrated the presence of S channels in sensory neuron growth cones. Application of serotonin to the bath produced long-lasting all-or-none closures of these channels in a manner identical to the previously characterized action of 5-HT in the cell body. Thus, channel modulation is not restricted to the cell body and probably occurs throughout the sensory neuron. This strengthens the view that S-channel modulation may also occur at the sensory neuron presynaptic terminal, where it could play a role in the presynaptic facilitation produced by 5-HT.

  19. 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

  20. Markov models of use-dependence and reverse use-dependence during the mouse cardiac action potential.

    Directory of Open Access Journals (Sweden)

    Qinlian Zhou

    Full Text Available The fast component of the cardiac transient outward current, I(Ktof, is blocked by a number of drugs. The major molecular bases of I(Ktof are Kv4.2/Kv4.3 voltage-gated potassium channels. Drugs with similar potencies but different blocking mechanisms have differing effects on action potential duration (APD. We used in silico analysis to determine the effect of I(Ktof-blocking drugs with different blocking mechanisms on mouse ventricular myocytes. We used our existing mouse model of the action potential, and developed 4 new Markov formulations for I(Ktof, I(Ktos, I(Kur, I(Ks. We compared effects of theoretical I(Ktof-specific channel blockers: (1 a closed state, and (2 an open channel blocker. At concentrations lower or close to IC(50, the drug which bound to the open state always had a much greater effect on APD than the drug which bound to the closed state. At concentrations much higher than IC(50, both mechanisms had similar effects at very low pacing rates. However, an open state binding drug had a greater effect on APD at faster pacing rates, particularly around 10 Hz. In summary, our data indicate that drug effects on APD are strongly dependent not only on IC(50, but also on the drug binding state.

  1. 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.

  2. The characteristics of action potential and nonselec-tive cation current of cardiomyocytes in rabbit superior vena cava

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    As a special focus in initiating and maintaining atrial fibrillation (AF), cardiomyocytes in superior vena cava (SVC) have distinctive electrophysiological characters. In this study, we found that comparing with the right atrial (RA) cardiomyoctyes, the SVC cardiomyoctyes had longer APD90 at the different basic cycle lengths; the conduction block could be observed on both RA and SVC cardiomyoctyes. A few of SVC cardiomyoctyes showed slow response action potentials with automatic activity and some others showed early afterdepolarization (EAD) spontaneously. Further more, we found that there are nonselective cation current (INs) in both SVC and RA cardiomyocytes. The peak density of INs in SVC cardiomyocytes was smaller than that in RA cardiomyocytes. Removal of extracellular divalent cation and glucose could increase INs in SVC cardiomyocytes. The agonist or the antagonist of INs may in-crease or decrease APD. To sum up, some SVC cardiomyocytes possess the ability of spontaneous activity; the difference of transmembrane action potentials between SVC and RA cardiomyocytes is partly because of the different density of INs between them; the agonist or the antagonist of INs can in-crease or decrease APD leading to the enhancement or reduction of EAD genesis in SVC cardiomyo-cytes. INs in rabbit myocytes is fairly similar to TRPC3 current in electrophysiological property, which might play an important role in the mechanisms of AF.

  3. Effects of changes in frequency on guinea pig ventricular action potential duration and on QT interval under different experimental conditions.

    Science.gov (United States)

    von Savigny, L; Hohnloser, S; Antoni, H

    1981-01-01

    Isolated perfused guinea pig hearts (Langendorff preparation) were arrested by carbachol (0.1-0.2 mg/l) and electrically stimulated in the region of the av-conducting system. The QT interval was determined by means of extracellular electrodes at different driving frequencies. Separate experiments were performed on papillary muscles from the right ventricle to measure the duration of the transmembrane action potential under comparable conditions. At 35 degrees C (Ke+ 5.4 mmol/l) increasing the frequency of stimulation (range 12-120/min) caused the action potential duration (APD) to decrease to a greater extent than the QT interval. Stepwise rising of the external K+ concentration up to 16.2 mmol/l produced a nearly parallel shift to the APD-frequency relation to lower values. Again, the QT interval was less affected by increasing the external K+ concentration than the APD. Stepwise reduction of the temperature down to 20 degrees C prolonged the APD as well as the QT interval, the effects being more pronounced at lower than at higher stimulation frequencies. Under all examined experimental conditions, the APD proved to be markedly shorter than the QT interval even when the latter is diminished by the duration of QRS. The results suggest that no close relation exists between the APD and the QT interval. The observed divergencies may be due to functional differences among various parts of the ventricles.

  4. Changes in intracellular calcium concentration influence beat-to-beat variability of action potential duration in canine ventricular myocytes.

    Science.gov (United States)

    Kistamas, K; Szentandrassy, N; Hegyi, B; Vaczi, K; Ruzsnavszky, F; Horvath, B; Banyasz, T; Nanasi, P P; Magyar, J

    2015-02-01

    The aim of the present work was to study the influence of changes in intracellular calcium concentration ([Ca(2+)]i) on beat-to-beat variability (short term variability, SV) of action potential duration (APD) in isolated canine ventricular cardiomyocytes. Series of action potentials were recorded from enzymatically isolated canine ventricular cells using conventional microelectrode technique. Drug effects on SV were evaluated as relative SV changes determined by plotting the drug-induced changes in SV against corresponding changes in APD and comparing these data to the exponential SV-APD function obtained with inward and outward current injections. Exposure of myocytes to the Ca(2+) chelator BAPTA-AM (5 μM) decreased, while Ca(2+) ionophore A23187 (1 μM) increased the magnitude of relative SV. Both effects were primarily due to the concomitant changes in APD. Relative SV was reduced by BAPTA-AM under various experimental conditions including pretreatment with veratridine, BAY K8644, dofetilide or E-4031. Contribution of transient changes of [Ca(2+)]i due to Ca(2+) released from the sarcoplasmic reticulum (SR) was studied using 10 μM ryanodine and 1 μM cyclopiazonic acid: relative SV was reduced by both agents. Inhibition of the Na(+)-Ca(2+) exchanger by 1 μM SEA0400 increased relative SV. It is concluded that elevation of [Ca(2+)]i increases relative SV significantly. More importantly, Ca(2+) released from the SR is an important component of this effect.

  5. Understanding Implicit Bias: What Educators Should Know

    Science.gov (United States)

    Staats, Cheryl

    2016-01-01

    The desire to ensure the best for children is precisely why educators should become aware of the concept of implicit bias: the attitudes or stereotypes that affect our understanding, actions, and decisions in an unconscious manner. Operating outside of our conscious awareness, implicit biases are pervasive, and they can challenge even the most…

  6. Potential food applications of biobased materials. An EU- concerted action project

    DEFF Research Database (Denmark)

    Haugaard, V.K.; Udsen, A.M.; Mortensen, G.

    2001-01-01

    and coatings to food but novel commercial applications of these are scarce. Based on information currently available on the properties of biobased packaging materials the study identified products in the fresh meat, dairy, ready meal, beverage, fruit and vegetable, snack, frozen food and dry food categories......The objective of the study was to ascertain the state of the art with regard to the applicability of biobased packaging materials to foods and to identify potential food applications for biobased materials. The study revealed relatively few examples of biobased materials used as primary, secondary...... or tertiary packaging materials for foods. This is due to the fact that published investigations on the use of biobased materials are still scarce, and results obtained remain unpublished because of commercial pressures. The scientific literature contains numerous reports on applications of edible films...

  7. MIF-1 potentiates the action of tricyclic antidepressants in an animal model of depression.

    Science.gov (United States)

    Kostowski, W; Danysz, W; Dyr, W; Jankowska, E; Krzaścik, P; Pałejko, W; Stefański, R; Płaźnik, A

    1991-01-01

    In the present paper, the effect of simultaneous treatment of rats with low doses of MIF-1 and tricyclic antidepressants on rat behavior in the forced swim test was studied. It was found that MIF-1 stimulated in a dose-dependent manner "active" behavior of animals in this paradigm. The effect of MIF-1 appeared to be independent of changes in rats' locomotion in the open field test. The combined treatment of rats with MIF-1 (0.01 mg/kg IP) and amitriptyline (5 mg/kg IP) or desipramine (1.25 mg/kg) IP) significantly stimulated active behavior in the forced swim test above the level obtained with each of the drugs given separately. The present data suggest the potential clinical efficacy of a combined therapy of depressive patients with MIF-1 and small doses of tricyclic antidepressants.

  8. 'Working' cardiomyocytes exhibiting plateau action potentials from human placenta-derived extraembryonic mesodermal cells.

    Science.gov (United States)

    Okamoto, Kazuma; Miyoshi, Shunichiro; Toyoda, Masashi; Hida, Naoko; Ikegami, Yukinori; Makino, Hatsune; Nishiyama, Nobuhiro; Tsuji, Hiroko; Cui, Chang-Hao; Segawa, Kaoru; Uyama, Taro; Kami, Daisuke; Miyado, Kenji; Asada, Hironori; Matsumoto, Kenji; Saito, Hirohisa; Yoshimura, Yasunori; Ogawa, Satoshi; Aeba, Ryo; Yozu, Ryohei; Umezawa, Akihiro

    2007-07-15

    The clinical application of cell transplantation for severe heart failure is a promising strategy to improve impaired cardiac function. Recently, an array of cell types, including bone marrow cells, endothelial progenitors, mesenchymal stem cells, resident cardiac stem cells, and embryonic stem cells, have become important candidates for cell sources for cardiac repair. In the present study, we focused on the placenta as a cell source. Cells from the chorionic plate in the fetal portion of the human placenta were obtained after delivery by the primary culture method, and the cells generated in this study had the Y sex chromosome, indicating that the cells were derived from the fetus. The cells potentially expressed 'working' cardiomyocyte-specific genes such as cardiac myosin heavy chain 7beta, atrial myosin light chain, cardiac alpha-actin by gene chip analysis, and Csx/Nkx2.5, GATA4 by RT-PCR, cardiac troponin-I and connexin 43 by immunohistochemistry. These cells were able to differentiate into cardiomyocytes. Cardiac troponin-I and connexin 43 displayed a discontinuous pattern of localization at intercellular contact sites after cardiomyogenic differentiation, suggesting that the chorionic mesoderm contained a large number of cells with cardiomyogenic potential. The cells began spontaneously beating 3 days after co-cultivation with murine fetal cardiomyocytes and the frequency of beating cells reached a maximum on day 10. The contraction of the cardiomyocytes was rhythmical and synchronous, suggesting the presence of electrical communication between the cells. Placenta-derived human fetal cells may be useful for patients who cannot supply bone marrow cells but want to receive stem cell-based cardiac therapy.

  9. Methanol extract of Tephrosia vogelii leaves potentiates the contractile action of acetylcholine on isolated rabbit jejunum

    Institute of Scientific and Technical Information of China (English)

    Tavershima Dzenda; Joseph Olusegun Ayo; Alexander Babatunde Adelaiye; Ambrose Osemattah Adaudi

    2015-01-01

    To investigate the modulating role of methanol extract of Tephrosia vogelii leaves on acetylcholine (ACh)-induced contraction of isolated rabbit jejunum. Methods: Rabbit jejunum segment was removed and placed in an organ bath containing Tyrode’s solution, and its contractions were recorded isometrically. Results: ACh (2.0 × 10-10 g/mL) and the extract (2.0 × 10-4 g/mL) individually increased the frequency of contraction (mean ± SEM) of the isolated smooth muscle tissue by 47.6% ± 9.5%and 77.8% ± 66.5%, respectively. When ACh and the extract were combined, the frequency of contraction of the tissue was increased by 222.2% ± 25.9%, representing a 366.7% increase (P < 0.001) over the effect of ACh alone. Similarly, ACh (2.0 × 10-9 g/mL) and the extract individually increased significantly (P < 0.001) the amplitude of contraction of the tissue by 685.7% ± 61.1% and 455.2% ± 38.1%, respectively. When ACh and the extract were combined, the amplitude of contraction of the tissue rose by 1263.8% ± 69.0%, representing 84.3% increase over the effect of ACh alone. Conclusions: The findings demonstrate that methanol extract of Tephrosia vogelii leaves potentiates the contractile effect of ACh on intestinal smooth muscle, supporting the traditional claim that the plant is purgative.

  10. Potentials of Mangifera indica in the treatment of depressive-anxiety disorders: possible mechanisms of action.

    Science.gov (United States)

    Ishola, Ismail O; Awodele, Olufunsho; Eluogu, Chinedum O

    2016-09-01

    Mangifera indica (Anacardiaceae) is an important herb in the traditional African and Ayurvedic medicines. The stem barks are used in the treatment of hypertension, insomnia, tumour, depression, rheumatism and as a tonic. This study was carried out to investigate antidepressant- and anxiolytic-like effect of the hydroethanol stem bark extract of M. indica (HeMI) in mice. HeMI (12.5-100 mg/kg, p.o.) was administered 1 h before subjecting the animal to the forced swim test (FST), tail suspension test (TST) and elevated plus maze tests (EPM). HeMI (12.5-100 mg/kg, p.o.) treatment produced significant reduction in immobility time [F(6.56)=8.35, pantidepressant-like effect elicited by HeMI. In the EPM, HeMI produced significant [F(5,42)=8.91, pantidepressant-like effect of M. indica through interaction with 5-HT2 receptor, α2-adrenoceptor and dopamine D2-receptors. Also, an anxiolytic-like effect through its affinity for 5-HT2 and benzodiazepine receptors. Hence, M. indica could be a potential phytotherapeutic agent in the treatment of mixed anxiety-depressive illness.

  11. Control of Postharvest Bacterial Soft Rot by Gamma Irradiation and its Potential Modes of Action

    Directory of Open Access Journals (Sweden)

    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.

  12. The hyperpolarization-activated channel HCN4 is required for the generation of pacemaker action potentials in the embryonic heart

    Science.gov (United States)

    Stieber, Juliane; Herrmann, Stefan; Feil, Susanne; Löster, Jana; Feil, Robert; Biel, Martin; Hofmann, Franz; Ludwig, Andreas

    2003-01-01

    Hyperpolarization-activated, cyclic nucleotide-gated cation currents, termed If or Ih, are generated by four members of the hyperpolarization-activated, cyclic nucleotide-gated cation (HCN) channel family. These currents have been proposed to contribute to several functions including pacemaker activity in heart and brain, control of resting potential, and neuronal plasticity. Transcripts of the HCN4 isoform have been found in cardiomyocytes and neurons, but the physiological role of this channel is unknown. Here we show that HCN4 is essential for the proper function of the developing cardiac conduction system. In wild-type embryos, HCN4 is highly expressed in the cardiac region where the early sinoatrial node develops. Mice lacking HCN4 channels globally, as well as mice with a selective deletion of HCN4 in cardiomyocytes, died between embryonic days 9.5 and 11.5. On average, If in cardiomyocytes from mutant embryos is reduced by 85%. Hearts from HCN4-deficient embryos contracted significantly slower compared with wild type and could not be stimulated by cAMP. In both wild-type and HCN4-/- mice, cardiac cells with “primitive” pacemaker action potentials could be found. However, cardiac cells with “mature” pacemaker potentials, observed in wild-type embryos starting at day 9.0, were not detected in HCN4-deficient embryos. Thus, HCN4 channels are essential for the proper generation of pacemaker potentials in the emerging sinoatrial node. PMID:14657344

  13. 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.

  14. Potassium conductances mediate bidirectional state-dependent modulation of action potential evoked dendritic calcium signals in dentate gyrus granule cells

    Directory of Open Access Journals (Sweden)

    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. Methanol extract of Tephrosia vogelii leaves potentiates the contractile action of acetylcholine on isolated rabbit jejunum

    Institute of Scientific and Technical Information of China (English)

    Tavershima; Dzenda; Joseph; Olusegun; Ayo; Alexander; Babatunde; Adelaiye; Ambrose; Osemattah; Adaudi

    2015-01-01

    Objective:To investigate the modulating role of methanol extract of Tephrosia vogelii leaves on acetylcholine(ACh)-induced contraction of isolated rabbit jejunum.Methods: Rabbit jejunum segment was removed and placed in an organ bath containing Tyrode’s solution, and its contractions were recorded isometrically.Results: ACh(2.0 × 10-10 g/m L) and the extract(2.0 × 10-4 g/m L) individually increased the frequency of contraction(mean ± SEM) of the isolated smooth muscle tissue by 47.6% ± 9.5% and 77.8% ± 66.5%, respectively. When ACh and the extract were combined, the frequency of contraction of the tissue was increased by 222.2% ± 25.9%, representing a 366.7% increase(P < 0.001) over the effect of ACh alone. Similarly, ACh(2.0 × 10-9 g/m L) and the extract individually increased significantly(P < 0.001) the amplitude of contraction of the tissue by 685.7% ± 61.1% and 455.2% ± 38.1%, respectively. When ACh and the extract were combined, the amplitude of contraction of the tissue rose by 1263.8% ± 69.0%, representing 84.3% increase over the ef ect of ACh alone. Conclusions: The findings demonstrate that methanol extract of Tephrosia vogelii leaves potentiates the contractile ef ect of ACh on intestinal smooth muscle, supporting the traditional claim that the plant is purgative.

  16. Exploring potential mechanisms of action of natalizumab in secondary progressive multiple sclerosis.

    Science.gov (United States)

    Sellebjerg, Finn; Cadavid, Diego; Steiner, Deborah; Villar, Luisa Maria; Reynolds, Richard; Mikol, Daniel

    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, to exert beneficial effects in reducing disease progression unrelated to relapses in SPMS. In both forms of MS, active brain-tissue injury is associated with inflammation; but in SPMS, the inflammatory response occurs at least partly behind the blood-brain barrier and is followed by a cascade of events, including persistent microglial activation that may lead to chronic demyelination and neurodegeneration associated with irreversible disability. In patients with relapsing forms of MS, natalizumab therapy is known to significantly reduce intrathecal inflammatory responses which results in reductions 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, axonal damage and demyelination, and has demonstrated the ability to reduce innate immune activation and intrathecal immunoglobulin synthesis in patients with MS. The efficacy of natalizumab therapy in SPMS is currently being investigated in a randomized, double-blind, placebo-controlled trial.

  17. Mapping HIV-1 vaccine induced T-cell responses: bias towards less-conserved regions and potential impact on vaccine efficacy in the Step study.

    Directory of Open Access Journals (Sweden)

    Fusheng Li

    Full Text Available T cell directed HIV vaccines are based upon the induction of CD8+ T cell memory responses that would be effective in inhibiting infection and subsequent replication of an infecting HIV-1 strain, a process that requires a match or near-match between the epitope induced by vaccination and the infecting viral strain. We compared the frequency and specificity of the CTL epitope responses elicited by the replication-defective Ad5 gag/pol/nef vaccine used in the Step trial with the likelihood of encountering those epitopes among recently sequenced Clade B isolates of HIV-1. Among vaccinees with detectable 15-mer peptide pool ELISpot responses, there was a median of four (one Gag, one Nef and two Pol CD8 epitopes per vaccinee detected by 9-mer peptide ELISpot assay. Importantly, frequency analysis of the mapped epitopes indicated that there was a significant skewing of the T cell response; variable epitopes were detected more frequently than would be expected from an unbiased sampling of the vaccine sequences. Correspondingly, the most highly conserved epitopes in Gag, Pol, and Nef (defined by presence in >80% of sequences currently in the Los Alamos database www.hiv.lanl.gov were detected at a lower frequency than unbiased sampling, similar to the frequency reported for responses to natural infection, suggesting potential epitope masking of these responses. This may be a generic mechanism used by the virus in both contexts to escape effective T cell immune surveillance. The disappointing results of the Step trial raise the bar for future HIV vaccine candidates. This report highlights the bias towards less-conserved epitopes present in the same vaccine used in the Step trial. Development of vaccine strategies that can elicit a greater breadth of responses, and towards conserved regions of the genome in particular, are critical requirements for effective T-cell based vaccines against HIV-1.ClinicalTrials.gov NCT00849680, A Study of Safety, Tolerability

  18. Testing for Bias against Female Test Takers of the Graduate Management Admissions Test and Potential Impact on Admissions to Graduate Programs in Business.

    Science.gov (United States)

    Wright, Robert E.; Bachrach, Daniel G.

    2003-01-01

    Graduate Management Admission Test (GMAT) scores and grade point average in graduate core courses were compared for 190 male and 144 female business administration students. No significant differences in course performance were found, but males had been admitted with significantly higher GMAT scores, suggesting a bias against women. (Contains 27…

  19. Testing for Bias against Female Test Takers of the Graduate Management Admissions Test and Potential Impact on Admissions to Graduate Programs in Business.

    Science.gov (United States)

    Wright, Robert E.; Bachrach, Daniel G.

    2003-01-01

    Graduate Management Admission Test (GMAT) scores and grade point average in graduate core courses were compared for 190 male and 144 female business administration students. No significant differences in course performance were found, but males had been admitted with significantly higher GMAT scores, suggesting a bias against women. (Contains 27…

  20. Interwell radiative recombination in the presence of random potential fluctuations in GaAs/AlGaAs biased double quantum wells

    DEFF Research Database (Denmark)

    Timofeev, V.B.; Larionov, A.V.; Ioselevich, A.S.;

    1998-01-01

    The interwell radiative recombination from biased double quantum wells (DQW) in pin GaAs/AlGaAs heterostructures is investigated at different temperatures and external electrical fields. The luminescence line of interwell recombination of spatially separated electron-hole pairs exhibits systemati...

  1. A Simulation Platform for Quantifying Survival Bias

    DEFF Research Database (Denmark)

    Mayeda, Elizabeth Rose; Tchetgen Tchetgen, Eric J; Power, Melinda C

    2016-01-01

    Bias due to selective mortality is a potential concern in many studies and is especially relevant in cognitive aging research because cognitive impairment strongly predicts subsequent mortality. Biased estimation of the effect of an exposure on rate of cognitive decline can occur when mortality i......-mortality situations. This simulation platform provides a flexible tool for evaluating biases in studies with high mortality, as is common in cognitive aging research.......Bias due to selective mortality is a potential concern in many studies and is especially relevant in cognitive aging research because cognitive impairment strongly predicts subsequent mortality. Biased estimation of the effect of an exposure on rate of cognitive decline can occur when mortality...... platform with which to quantify the expected bias in longitudinal studies of determinants of cognitive decline. We evaluated potential survival bias in naive analyses under several selective survival scenarios, assuming that exposure had no effect on cognitive decline for anyone in the population. Compared...

  2. Slow recovery from inactivation of Na+ channels underlies the activity-dependent attenuation of dendritic action potentials in hippocampal CA1 pyramidal neurons.

    Science.gov (United States)

    Colbert, C M; Magee, J C; Hoffman, D A; Johnston, D

    1997-09-01

    Na+ action potentials propagate into the dendrites of pyramidal neurons driving an influx of Ca2+ that seems to be important for associative synaptic plasticity. During repetitive (10-50 Hz) firing, dendritic action potentials display a marked and prolonged voltage-dependent decrease in amplitude. Such a decrease is not apparent in somatic action potentials. We investigated the mechanisms of the different activity dependence of somatic and dendritic action potentials in CA1 pyramidal neurons of adult rats using whole-cell and cell-attached patch-clamp methods. There were three main findings. First, dendritic Na+ currents decreased in amplitude when repeatedly activated by brief (2 msec) depolarizations. Recovery was slow and voltage-dependent. Second, Na+ currents decreased much less in somatic than in dendritic patches. Third, although K+ currents remained constant during trains, K+ currents were necessary for dendritic action potential amplitude to decrease in whole-cell experiments. These results suggest that regional differences in Na+ and K+ channels determine the differences in the activity dependence of somatic and dendritic action potential amplitudes.

  3. Cordycepin Decreases Compound Action Potential Conduction of Frog Sciatic Nerve In Vitro Involving Ca2+-Dependent Mechanisms

    Directory of Open Access Journals (Sweden)

    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.

  4. 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.

  5. Role of AMPA and NMDA receptors and back-propagating action potentials in spike timing-dependent plasticity.

    Science.gov (United States)

    Fuenzalida, Marco; Fernández de Sevilla, David; Couve, Alejandro; Buño, Washington

    2010-01-01

    The cellular mechanisms that mediate spike timing-dependent plasticity (STDP) are largely unknown. We studied in vitro in CA1 pyramidal neurons the contribution of AMPA and N-methyl-d-aspartate (NMDA) components of Schaffer collateral (SC) excitatory postsynaptic potentials (EPSPs; EPSP(AMPA) and EPSP(NMDA)) and of the back-propagating action potential (BAP) to the long-term potentiation (LTP) induced by a STDP protocol that consisted in pairing an EPSP and a BAP. Transient blockade of EPSP(AMPA) with 7-nitro-2,3-dioxo-1,4-dihydroquinoxaline-6-carbonitrile (CNQX) during the STDP protocol prevented LTP. Contrastingly LTP was induced under transient inhibition of EPSP(AMPA) by combining SC stimulation, an imposed EPSP(AMPA)-like depolarization, and BAP or by coupling the EPSP(NMDA) evoked under sustained depolarization (approximately -40 mV) and BAP. In Mg(2+)-free solution EPSP(NMDA) and BAP also produced LTP. Suppression of EPSP(NMDA) or BAP always prevented LTP. Thus activation of NMDA receptors and BAPs are needed but not sufficient because AMPA receptor activation is also obligatory for STDP. However, a transient depolarization of another origin that unblocks NMDA receptors and a BAP may also trigger LTP.

  6. Cyclopiazonic acid disturbs the regulation of cytosolic calcium when repetitive action potentials are evoked in Dionaea traps.

    Science.gov (United States)

    Trebacz, Kazimierz; Busch, Marion B; Hejnowicz, Zygmunt; Sievers, Andreas

    1996-04-01

    Evoking of action potentials (APs) in the trap of Dionaea muscipula Ellis at intervals shorter than 20 s caused a gradual decrease in the amplitude of the APs. At longer intervals the amplitude was constant. The calcium ionophore A23187 (1 μM) caused a considerable decrease of AP amplitude. Pretreatment of a segment of the Dionaea trap with cyclopiazonic acid (CPA), which is a specific inhibitor of the Ca(2+)-ATPase in the sarcoplasmic seticulum of animal cells and in ER vesicles isolated from plant cells, only slightly affected the amplitude when APs were evoked every 10 min; however, it caused a considerable decrease in the amplitude when the stimulation was repeated every 2 min. Assuming that APs increase the concentration of cytosolic Ca(2+) and the amplitude of AP depends on the gradient of Ca(2+) across the plasma membrane, the effect of CPA on the AP amplitude indicates that CPA inhibits the sequestration of Ca(2+) in Dionaea cells.

  7. 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.

  8. Dendritic Na(+) spikes enable cortical input to drive action potential output from hippocampal CA2 pyramidal neurons.

    Science.gov (United States)

    Sun, Qian; Srinivas, Kalyan V; Sotayo, Alaba; Siegelbaum, Steven A

    2014-01-01

    Synaptic inputs from different brain areas are often targeted to distinct regions of neuronal dendritic arbors. Inputs to proximal dendrites usually produce large somatic EPSPs that efficiently trigger action potential (AP) output, whereas inputs to distal dendrites are greatly attenuated and may largely modulate AP output. In contrast to most other cortical and hippocampal neurons, hippocampal CA2 pyramidal neurons show unusually strong excitation by their distal dendritic inputs from entorhinal cortex (EC). In this study, we demonstrate that the ability of these EC inputs to drive CA2 AP output requires the firing of local dendritic Na(+) spikes. Furthermore, we find that CA2 dendritic geometry contributes to the efficient coupling of dendritic Na(+) spikes to AP output. These results provide a striking example of how dendritic spikes enable direct cortical inputs to overcome unfavorable distal synaptic locale to trigger axonal AP output and thereby enable efficient cortico-hippocampal information flow.

  9. Novel MEA Platform with PDMS Microtunnels Enables Detection of Action Potential Propagation from Isolated Axons in Culture

    Science.gov (United States)

    Dworak, Bradley J.; Wheeler, Bruce C.

    2008-01-01

    This study investigated a novel multi-electrode-array (MEA) design capable of long-term and highly selective recordings of axonal signals using PDMS microtunnels. We successfully grew neurons in culture so that only axons extended through narrow (10 µm wide by 3 µm high) and long (750 µm) microtunnels under which multiple electrodes were integrated. This permitted the recording of relatively large (up to 200 µV) electrical signals, including the propagation speed and direction of these travelling action potentials. To further demonstrate the operation of the device as a diagnostic tool for drug screening assays, the drug mepivacaine was applied in washout experiments. Here, we identified significant changes in mean spiking rate and conduction velocity. PMID:19156289

  10. 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

  11. Responses of action potential and K+ currents to temperature acclimation in fish hearts: phylogeny or thermal preferences?

    Science.gov (United States)

    Haverinen, Jaakko; Vornanen, Matti

    2009-01-01

    Electrical activity of the heart is assumed to be one of the key factors that set thermal tolerance limits for ectothermic vertebrates. Therefore, we hypothesized that in thermal acclimation--the duration of cardiac action potential and the repolarizing K+ currents that regulate action potential duration (APD)--the rapid component of the delayed rectifier K+ current (I(Kr)) and the inward rectifier K+ current (I(K1)) are more plastic in eurythermal than in stenothermal fish species. The hypothesis was tested in six freshwater teleosts representing four different fish orders (Cadiformes, Cypriniformes, Perciformes, Salmoniformes) acclimated at +4 degrees C (cold acclimation) or +18 degrees C (warm acclimation). In cold acclimation, a compensatory shortening of APD occurred in all species regardless of thermal tolerances, life styles, or phylogenies of the fish, suggesting that this response is a common characteristic of the teleost heart. The strength of the response did not, however, obey simple eurythermy-stenothermy gradation but differed among the phylogenetic groups. Salmoniformes fish showed the greatest acclimation capacity of cardiac electrical activity, whereas the weakest response appeared in the perch (Perciformes) heart. The underlying ionic mechanisms were also partly phylogeny dependent. Modification of the I(Kr) current was al- most ubiquitously involved in acclimation response of fish cardiac myocytes to temperature, while the ability to change the I(K1) current under chronic thermal stress was absent or showed inverse compensation in Salmoniformes species. Thus, in Salmoniformes fish, the thermal plasticity of APD is strongly based on I(Kr), while other fish groups rely on both I(Kr) and I(K1).

  12. Effects of the histamine H1 receptor antagonist hydroxyzine on hERG K+ channels and cardiac action potential duration

    Institute of Scientific and Technical Information of China (English)

    Byung Hoon LEE; Seung Ho LEE; Daehyun CHU; Jin Won HYUN; Han CHOE; Bok Hee CHOI; Su-Hyun JO

    2011-01-01

    To investigate the effects of hydroxyzine on human ether-a-go-go-related gene (hERG) channels to determine the electrolphysiological basis for its proarrhythmic effects.Methods:hERG channels were expressed in Xenopus oocytes and HEK293 cells,and the effects of hydroxyzine on the channels were examined using two-microelectrode voltage-clamp and patch-clamp techniques,respectively.The effects of hydroxyzine on action potential duration were examined in guinea pig ventricular myocytes using current clamp.Results:Hydroxyzine (0.2 and 2 μmol/L) significantly increased the action potential duration at 90% repolarization (APD90) in both concentration- and time-dependent manners.Hydroxyzine (0.03-3 μmol/L) blocked both the steady-state and tail hERG currents.The block was voltage-dependent,and the values of IC50 for blocking the steady-state and tail currents at +20 mV was 0.18±0.02 μmol/L and 0.16±0.01 μmol/L,respectively,in HEK293 cells.Hydroxyzine (5 μmol/L) affected both the activated and the inactivated states of the channels,but not the closed state.The S6 domain mutation Y652A attenuated the blocking of hERG current by ~6-fold.Conclusion:The results suggest that hydroxyzine could block hERG channels and prolong APD.The tyrosine at position 652 in the channel may be responsible for the proarrhythmic effects of hydroxyzine.

  13. Spine calcium transients induced by synaptically-evoked action potentials can predict synapse location and establish synaptic democracy.

    Directory of Open Access Journals (Sweden)

    David C Sterratt

    Full Text Available 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.

  14. 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

  15. The effects of propofol on local field potential spectra, action potential firing rate, and their temporal relationship in humans and felines

    Directory of Open Access Journals (Sweden)

    Sara eHanrahan

    2013-04-01

    Full Text Available 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.

  16. Cognitive Bias in Systems Verification

    Science.gov (United States)

    Larson, Steve

    2012-01-01

    Working definition of cognitive bias: Patterns by which information is sought and interpreted that can lead to systematic errors in decisions. Cognitive bias is used in diverse fields: Economics, Politics, Intelligence, Marketing, to name a few. Attempts to ground cognitive science in physical characteristics of the cognitive apparatus exceed our knowledge. Studies based on correlations; strict cause and effect is difficult to pinpoint. Effects cited in the paper and discussed here have been replicated many times over, and appear sound. Many biases have been described, but it is still unclear whether they are all distinct. There may only be a handful of fundamental biases, which manifest in various ways. Bias can effect system verification in many ways . Overconfidence -> Questionable decisions to deploy. Availability -> Inability to conceive critical tests. Representativeness -> Overinterpretation of results. Positive Test Strategies -> Confirmation bias. Debiasing at individual level very difficult. The potential effect of bias on the verification process can be managed, but not eliminated. Worth considering at key points in the process.

  17. Cognitive Bias in Systems Verification

    Science.gov (United States)

    Larson, Steve

    2012-01-01

    Working definition of cognitive bias: Patterns by which information is sought and interpreted that can lead to systematic errors in decisions. Cognitive bias is used in diverse fields: Economics, Politics, Intelligence, Marketing, to name a few. Attempts to ground cognitive science in physical characteristics of the cognitive apparatus exceed our knowledge. Studies based on correlations; strict cause and effect is difficult to pinpoint. Effects cited in the paper and discussed here have been replicated many times over, and appear sound. Many biases have been described, but it is still unclear whether they are all distinct. There may only be a handful of fundamental biases, which manifest in various ways. Bias can effect system verification in many ways . Overconfidence -> Questionable decisions to deploy. Availability -> Inability to conceive critical tests. Representativeness -> Overinterpretation of results. Positive Test Strategies -> Confirmation bias. Debiasing at individual level very difficult. The potential effect of bias on the verification process can be managed, but not eliminated. Worth considering at key points in the process.

  18. 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

  19. 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.

    2013-01-01

    Summary 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

  20. Potential role of monkey inferior parietal neurons coding action semantic equivalences as precursors of parts of speech

    Science.gov (United States)

    Yamazaki, Yumiko; Yokochi, Hiroko; Tanaka, Michio; Okanoya, Kazuo; Iriki, Atsushi

    2010-01-01

    The anterior portion of the inferior parietal cortex possesses comprehensive representations of actions embedded in behavioural contexts. Mirror neurons, which respond to both self-executed and observed actions, exist in this brain region in addition to those originally found in the premotor cortex. We found that parietal mirror neurons responded differentially to identical actions embedded in different contexts. Another type of parietal mirror neuron represents an inverse and complementary property of responding equally to dissimilar actions made by itself and others for an identical purpose. Here, we propose a hypothesis that these sets of inferior parietal neurons constitute a neural basis for encoding the semantic equivalence of various actions across different agents and contexts. The neurons have mirror neuron properties, and they encoded generalization of agents, differentiation of outcomes, and categorization of actions that led to common functions. By integrating the activities of these mirror neurons with various codings, we further suggest that in the ancestral primates' brains, these various representations of meaningful action led to the gradual establishment of equivalence relations among the different types of actions, by sharing common action semantics. Such differential codings of the components of actions might represent precursors to the parts of protolanguage, such as gestural communication, which are shared among various members of a society. Finally, we suggest that the inferior parietal cortex serves as an interface between this action semantics system and other higher semantic systems, through common structures of action representation that mimic language syntax. PMID:20119879

  1. Study of amplitude frequency spectra of the compound action potentials recorded from normal and M. leprae infected mice using Fourier series analysis.

    Science.gov (United States)

    Vidyasagar, P B; Lokhandwalla, M N; Damle, P S

    1986-01-01

    Compound action potentials recorded from normal and M. leprae infected mice sciatic nerves were analysed in frequency domain using Fourier Series Analysis. Changes in myelinated fibre potentials were detected as early as 2nd post-inoculation month. This technique could be further developed to aid in early diagnosis of leprosy.

  2. Action Learning: Avoiding Conflict or Enabling Action

    Science.gov (United States)

    Corley, Aileen; Thorne, Ann

    2006-01-01

    Action learning is based on the premise that action and learning are inextricably entwined and it is this potential, to enable action, which has contributed to the growth of action learning within education and management development programmes. However has this growth in action learning lead to an evolution or a dilution of Revan's classical…

  3. 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.

  4. Action Research: A Spiral Inquiry for Valid and Useful Knowledge

    Science.gov (United States)

    Moghaddam, Alireza

    2007-01-01

    This article discusses methodological and philosophical issues linked to action research. The concepts of subjectivity and objectivity--potential sources of bias that mislead researchers in dealing with these concepts--and how to cope with them are discussed. Controversial issues of truth in positivism, postpositivism, and other schools of…

  5. Effectiveness of elite female basketball players’ technical-tactic actions and ways for their improvement at stage of maximal realization of individual potentials

    Directory of Open Access Journals (Sweden)

    Sushko R.A.

    2015-08-01

    Full Text Available Purpose: study effectiveness of elite female basketball players’ technical-tactic actions and determine the ways for their improvement at stage of maximal realization of individual potentials. Material: the authors analyzed competition functioning’s indicators of female basketball players of national combined team of Ukraine and their age characteristics. Results: effectiveness of technical-tactic actions in structure of national female basketball players’ combined team of Ukraine competition functioning at European championship. The authors present: indicators of team composition; roles in team; won and lost games; quantity of scored and skipped points; technical-tactic actions; age of sportswomen. Age indicators of elite female basketball players at stage of maximal realization have been given. Conclusions: we have composed a list of the most important technical-tactic actions in competition functioning. We also outlined ways for their perfection at stage of maximal realization of individual potentials of elite female basketball players of different game roles.

  6. The role of dendritic action potentials and Ca2+ influx in the induction of homosynaptic long-term depression in hippocampal CA1 pyramidal neurons.

    Science.gov (United States)

    Christie, B R; Magee, J C; Johnston, D

    1996-01-01

    Long-term depression (LTD) of synaptic efficacy at CA1 synapses is believed to be a Ca(2+)-dependent process. We used high-speed fluorescence imaging and patch-clamp techniques to quantify the spatial distribution of changes in intracellular Ca2+ accompanying the induction of LTD at Schaffer collateral synapses in CA1 pyramidal neurons. Low-frequency stimulation (3 Hz), which was subthreshold for action potentials, produced small changes in [Ca2+]i and failed to elicit LTD. Increasing the stimulus strength so that action potentials were generated produced both robust LTD and increases in [Ca2+]i. Back-propagating action potentials at 3 Hz in the absence of synaptic stimulation also produced increases in [Ca2+]i, but failed to induce LTD. When subthreshold synaptic stimulation was paired with back-propagating action potentials, however, large increases in [Ca2+]i were observed and robust LTD was induced. The LTD was blocked by the N-methyl-D-aspartate receptor (NMDAr) antagonist APV, and stimulus-induced increases in [Ca2+]i were reduced throughout the neuron under these conditions. The LTD was also dependent on Ca2+ influx via voltage-gated Ca2+ channels (VGCCs), because LTD was severely attenuated or blocked by both nimodipine and Ni2+. These findings suggest that back-propagating action potentials can exert a powerful control over the induction of LTD and that both VGCCs and NMDArs are involved in the induction of this form of plasticity.

  7. Potential self-selection bias in a nested case-control study on indoor environmental factors and their association with asthma and allergic symptoms among pre-school children

    DEFF Research Database (Denmark)

    Bornehag, Carl-Gustaf; Sundell, Jan; Sigsgaard, T.;

    2006-01-01

    , including health, building characteristics of the home, and socioeconomic factors between participating and non-participating families in a nested case-control study on asthma and allergy among children. Information was collected in a baseline questionnaire to the parents of 14,077 children aged 1-6 years...... in a first step. In a second step 2,156 of the children were invited to participate in a case-control study. Of these, 198 cases and 202 controls were finally selected. For identifying potential selection bias, information concerning all invited families in the case-control study was obtained from...... the baseline questionnaire. Results show that there are several possible biases due to self-selection involved in an extensive study on the impact of the home environment on asthma and allergy among children. Factors associated with participating were high socioeconomic status of the family, more health...

  8. Awareness Reduces Racial Bias

    OpenAIRE

    2014-01-01

    Can raising awareness of racial bias subsequently reduce that bias? We address this question by exploiting the widespread media attention highlighting racial bias among professional basketball referees that occurred in May 2007 following the release of an academic study. Using new data, we confirm that racial bias persisted in the years after the study's original sample, but prior to the media coverage. Subsequent to the media coverage though, the bias completely disappeared. We examine poten...

  9. Enteral nutrients potentiate the intestinotrophic action of glucagon-like peptide-2 in association with increased insulin-like growth factor-I responses in rats

    DEFF Research Database (Denmark)

    Liu, Xiaowen; Murali, Sangita G; Holst, Jens Juul

    2008-01-01

    compared to GLP-2. This indicates that EN potentiates the intesti