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Sample records for action potential clamp

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

    Science.gov (United States)

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

    2017-01-01

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

  2. Molecular motions that shape the cardiac action potential: Insights from voltage clamp fluorometry.

    Science.gov (United States)

    Zhu, Wandi; Varga, Zoltan; Silva, Jonathan R

    2016-01-01

    Very recently, voltage-clamp fluorometry (VCF) protocols have been developed to observe the membrane proteins responsible for carrying the ventricular ionic currents that form the action potential (AP), including those carried by the cardiac Na(+) channel, NaV1.5, the L-type Ca(2+) channel, CaV1.2, the Na(+)/K(+) ATPase, and the rapid and slow components of the delayed rectifier, KV11.1 and KV7.1. This development is significant, because VCF enables simultaneous observation of ionic current kinetics with conformational changes occurring within specific channel domains. The ability gained from VCF, to connect nanoscale molecular movement to ion channel function has revealed how the voltage-sensing domains (VSDs) control ion flux through channel pores, mechanisms of post-translational regulation and the molecular pathology of inherited mutations. In the future, we expect that this data will be of great use for the creation of multi-scale computational AP models that explicitly represent ion channel conformations, connecting molecular, cell and tissue electrophysiology. Here, we review the VCF protocol, recent results, and discuss potential future developments, including potential use of these experimental findings to create novel computational models. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Dynamics of the inward rectifier K+ current during the action potential of guinea pig ventricular myocytes

    OpenAIRE

    Ibarra, J.; Morley, G.E.; Delmar, M.

    1991-01-01

    The potassium selective, inward rectifier current (IK1) is known to be responsible for maintaining the resting membrane potential of quiescent ventricular myocytes. However, the contribution of this current to the different phases of the cardiac action potential has not been adequately established. In the present study, we have used the action potential clamp (APC) technique to characterize the dynamic changes of a cesium-sensitive (i.e., Ik1) current which occur during the action potential. ...

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

    Science.gov (United States)

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

    2013-03-01

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

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

    Science.gov (United States)

    Furong, Liu; Shengtian, L I

    2016-05-25

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

  6. [Effects of dauricine on action potentials and slow inward currents of guinea pig ventricular papillary muscles].

    Science.gov (United States)

    Li, S N; Zhang, K Y

    1992-11-01

    Effects of dauricine (Dau) on the action potentials (AP), the slow action potentials (SAP), and the slow inward currents (Isi) of guinea pig ventricular papillary muscles were observed by means of intracellular microelectrode and single sucrose gap voltage clamp technique. In the early stage, Dau shortened action potential duration 100 (APD100) and effective refractory period (ERP) (ERP/APD ERP, and APD20, significantly decreased action potential amplitude (APA), maximum velocity (Vmax), and overshot (OS) (ERP/APD > 1; P SAP induced by isoprenaline (P < 0.01), and remarkably inhibited Isi (P < 0.01). The results suggested that Dau exerted an inhibitory effect on Na+, Ca2+, and K+ channels.

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

    NARCIS (Netherlands)

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

    2008-01-01

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

  8. Optical mapping of optogenetically shaped cardiac action potentials

    Science.gov (United States)

    Park, Sarah A.; Lee, Shin-Rong; Tung, Leslie; Yue, David T.

    2014-01-01

    Light-mediated silencing and stimulation of cardiac excitability, an important complement to electrical stimulation, promises important discoveries and therapies. To date, cardiac optogenetics has been studied with patch-clamp, multielectrode arrays, video microscopy, and an all-optical system measuring calcium transients. The future lies in achieving simultaneous optical acquisition of excitability signals and optogenetic control, both with high spatio-temporal resolution. Here, we make progress by combining optical mapping of action potentials with concurrent activation of channelrhodopsin-2 (ChR2) or halorhodopsin (eNpHR3.0), via an all-optical system applied to monolayers of neonatal rat ventricular myocytes (NRVM). Additionally, we explore the capability of ChR2 and eNpHR3.0 to shape action-potential waveforms, potentially aiding the study of short/long QT syndromes that result from abnormal changes in action potential duration (APD). These results show the promise of an all-optical system to acquire action potentials with precise temporal optogenetics control, achieving a long-sought flexibility beyond the means of conventional electrical stimulation. PMID:25135113

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

    Science.gov (United States)

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

    2014-07-07

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

  10. Effects of pioglitazone on cardiac ion currents and action potential morphology in canine ventricular myocytes.

    Science.gov (United States)

    Kistamás, Kornél; Szentandrássy, Norbert; Hegyi, Bence; Ruzsnavszky, Ferenc; Váczi, Krisztina; Bárándi, László; Horváth, Balázs; Szebeni, Andrea; Magyar, János; Bányász, Tamás; Kecskeméti, Valéria; Nánási, Péter P

    2013-06-15

    Despite its widespread therapeutical use there is little information on the cellular cardiac effects of the antidiabetic drug pioglitazone in larger mammals. In the present study, therefore, the concentration-dependent effects of pioglitazone on ion currents and action potential configuration were studied in isolated canine ventricular myocytes using standard microelectrode, conventional whole cell patch clamp, and action potential voltage clamp techniques. Pioglitazone decreased the maximum velocity of depolarization and the amplitude of phase-1 repolarization at concentrations ≥3 μM. Action potentials were shortened by pioglitazone at concentrations ≥10 μM, which effect was accompanied with significant reduction of beat-to-beat variability of action potential duration. Several transmembrane ion currents, including the transient outward K(+) current (Ito), the L-type Ca(2+) current (ICa), the rapid and slow components of the delayed rectifier K(+) current (IKr and IKs, respectively), and the inward rectifier K(+) current (IK1) were inhibited by pioglitazone under conventional voltage clamp conditions. Ito was blocked significantly at concentrations ≥3 μM, ICa, IKr, IKs at concentrations ≥10 μM, while IK1 at concentrations ≥30 μM. Suppression of Ito, ICa, IKr, and IK1 has been confirmed also under action potential voltage clamp conditions. ATP-sensitive K(+) current, when activated by lemakalim, was effectively blocked by pioglitazone. Accordingly, action potentials were prolonged by 10 μM pioglitazone when the drug was applied in the presence of lemakalim. All these effects developed rapidly and were readily reversible upon washout. In conclusion, pioglitazone seems to be a harmless agent at usual therapeutic concentrations. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Dynamic Action Potential Restitution Contributes to Mechanical Restitution in Right Ventricular Myocytes From Pulmonary Hypertensive Rats.

    Science.gov (United States)

    Hardy, Matthew E L; Pervolaraki, Eleftheria; Bernus, Olivier; White, Ed

    2018-01-01

    We investigated the steepened dynamic action potential duration (APD) restitution of rats with pulmonary artery hypertension (PAH) and right ventricular (RV) failure and tested whether the observed APD restitution properties were responsible for negative mechanical restitution in these myocytes. PAH and RV failure were provoked in male Wistar rats by a single injection of monocrotaline (MCT) and compared with saline-injected animals (CON). Action potentials were recorded from isolated RV myocytes at stimulation frequencies between 1 and 9 Hz. Action potential waveforms recorded at 1 Hz were used as voltage clamp profiles (action potential clamp) at stimulation frequencies between 1 and 7 Hz to evoke rate-dependent currents. Voltage clamp profiles mimicking typical CON and MCT APD restitution were applied and cell shortening simultaneously monitored. Compared with CON myocytes, MCT myocytes were hypertrophied; had less polarized diastolic membrane potentials; had action potentials that were triggered by decreased positive current density and shortened by decreased negative current density; APD was longer and APD restitution steeper. APD90 restitution was unchanged by exposure to the late Na + -channel blocker (5 μM) ranolazine or the intracellular Ca 2+ buffer BAPTA. Under AP clamp, stimulation frequency-dependent inward currents were smaller in MCT myocytes and were abolished by BAPTA. In MCT myocytes, increasing stimulation frequency decreased contraction amplitude when depolarization duration was shortened, to mimic APD restitution, but not when depolarization duration was maintained. We present new evidence that the membrane potential of PAH myocytes is less stable than normal myocytes, being more easily perturbed by external currents. These observations can explain increased susceptibility to arrhythmias. We also present novel evidence that negative APD restitution is at least in part responsible for the negative mechanical restitution in PAH myocytes. Thus

  12. 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....

  13. Simulation of action potential propagation in plants.

    Science.gov (United States)

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

    2011-12-21

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

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

    Science.gov (United States)

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

    2015-05-01

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

  15. Force-controlled patch clamp of beating cardiac cells.

    Science.gov (United States)

    Ossola, Dario; Amarouch, Mohamed-Yassine; Behr, Pascal; Vörös, János; Abriel, Hugues; Zambelli, Tomaso

    2015-03-11

    From its invention in the 1970s, the patch clamp technique is the gold standard in electrophysiology research and drug screening because it is the only tool enabling accurate investigation of voltage-gated ion channels, which are responsible for action potentials. Because of its key role in drug screening, innovation efforts are being made to reduce its complexity toward more automated systems. While some of these new approaches are being adopted in pharmaceutical companies, conventional patch-clamp remains unmatched in fundamental research due to its versatility. Here, we merged the patch clamp and atomic force microscope (AFM) techniques, thus equipping the patch-clamp with the sensitive AFM force control. This was possible using the FluidFM, a force-controlled nanopipette based on microchanneled AFM cantilevers. First, the compatibility of the system with patch-clamp electronics and its ability to record the activity of voltage-gated ion channels in whole-cell configuration was demonstrated with sodium (NaV1.5) channels. Second, we showed the feasibility of simultaneous recording of membrane current and force development during contraction of isolated cardiomyocytes. Force feedback allowed for a gentle and stable contact between AFM tip and cell membrane enabling serial patch clamping and injection without apparent cell damage.

  16. Action potential bursts in central snail neurons elicited by paeonol: roles of ionic currents

    Science.gov (United States)

    Chen, Yi-hung; Lin, Pei-lin; Hsu, Hui-yu; Wu, Ya-ting; Yang, Han-yin; Lu, Dah-yuu; Huang, Shiang-suo; Hsieh, Ching-liang; Lin, Jaung-geng

    2010-01-01

    Aim: To investigate the effects of 2′-hydroxy-4′-methoxyacetophenone (paeonol) on the electrophysiological behavior of a central neuron (right parietal 4; RP4) of the giant African snail (Achatina fulica Ferussac). Methods: Intracellular recordings and the two-electrode voltage clamp method were used to study the effects of paeonol on the RP4 neuron. Results: The RP4 neuron generated spontaneous action potentials. Bath application of paeonol at a concentration of ≥500 μmol/L reversibly elicited action potential bursts in a concentration-dependent manner. Immersing the neurons in Co2+-substituted Ca2+-free solution did not block paeonol-elicited bursting. Pretreatment with the protein kinase A (PKA) inhibitor KT-5720 or the protein kinase C (PKC) inhibitor Ro 31-8220 did not affect the action potential bursts. Voltage-clamp studies revealed that paeonol at a concentration of 500 μmol/L had no remarkable effects on the total inward currents, whereas paeonol decreased the delayed rectifying K+ current (IKD) and the fast-inactivating K+ current (IA). Application of 4-aminopyridine (4-AP 5 mmol/L), an inhibitor of IA, or charybdotoxin 250 nmol/L, an inhibitor of the Ca2+-activated K+ current (IK(Ca)), failed to elicit action potential bursts, whereas tetraethylammonium chloride (TEA 50 mmol/L), an IKD blocker, successfully elicited action potential bursts. At a lower concentration of 5 mmol/L, TEA facilitated the induction of action potential bursts elicited by paeonol. Conclusion: Paeonol elicited a bursting firing pattern of action potentials in the RP4 neuron and this activity relates closely to the inhibitory effects of paeonol on the IKD. PMID:21042287

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

    DEFF Research Database (Denmark)

    Lewandowski, Rebecca; Procida, Kristina; Vaidyanathan, Ravi

    2008-01-01

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

  19. Introducing the Action Potential to Psychology Students

    Science.gov (United States)

    Simon-Dack, Stephanie L.

    2014-01-01

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

  20. Photovoltaic panel clamp

    Science.gov (United States)

    Mittan, Margaret Birmingham [Oakland, CA; Miros, Robert H. J. [Fairfax, CA; Brown, Malcolm P [San Francisco, CA; Stancel, Robert [Loss Altos Hills, CA

    2012-06-05

    A photovoltaic panel clamp includes an upper and lower section. The interface between the assembled clamp halves and the module edge is filled by a flexible gasket material, such as EPDM rubber. The gasket preferably has small, finger like protrusions that allow for easy insertion onto the module edge while being reversed makes it more difficult to remove them from the module once installed. The clamp includes mounting posts or an integral axle to engage a bracket. The clamp also may include a locking tongue to secure the clamp to a bracket.

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

    Science.gov (United States)

    Molnar, Peter; Hickman, James J

    2014-01-01

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

  2. Insulated pipe clamp design

    International Nuclear Information System (INIS)

    Anderson, M.J.; Hyde, L.L.; Wagner, S.E.; Severud, L.K.

    1980-01-01

    Thin wall large diameter piping for breeder reactor plants can be subjected to significant thermal shocks during reactor scrams and other upset events. On the Fast Flux Test Facility, the addition of thick clamps directly on the piping was undesired because the differential metal temperatures between the pipe wall and the clamp could have significantly reduced the pipe thermal fatigue life cycle capabilities. Accordingly, an insulated pipe clamp design concept was developed. The design considerations and methods along with the development tests are presented. Special considerations to guard against adverse cracking of the insulation material, to maintain the clamp-pipe stiffness desired during a seismic event, to minimize clamp restraint on the pipe during normal pipe heatup, and to resist clamp rotation or spinning on the pipe are emphasized

  3. Insulated pipe clamp design

    International Nuclear Information System (INIS)

    Anderson, M.J.; Hyde, L.L.; Wagner, S.E.; Severud, L.K.

    1980-01-01

    Thin wall large diameter piping for breeder reactor plants can be subjected to significant thermal shocks during reactor scrams and other upset events. On the Fast Flux Test Facility, the addition of thick clamps directly on the piping was undesired because the differential metal temperatures between the pipe wall and the clamp could have significantly reduced the pipe thermal fatigue life cycle capabilities. Accordingly, an insulated pipe clamp design concept was developed. 5 refs

  4. Radial wedge flange clamp

    Science.gov (United States)

    Smith, Karl H.

    2002-01-01

    A radial wedge flange clamp comprising a pair of flanges each comprising a plurality of peripheral flat wedge facets having flat wedge surfaces and opposed and mating flat surfaces attached to or otherwise engaged with two elements to be joined and including a series of generally U-shaped wedge clamps each having flat wedge interior surfaces and engaging one pair of said peripheral flat wedge facets. Each of said generally U-shaped wedge clamps has in its opposing extremities apertures for the tangential insertion of bolts to apply uniform radial force to said wedge clamps when assembled about said wedge segments.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2017-04-01

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

  7. 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.

  8. Effects of Acetylcholine and Noradrenalin on Action Potentials of Isolated Rabbit Sinoatrial and Atrial Myocytes

    Science.gov (United States)

    Verkerk, Arie O.; Geuzebroek, Guillaume S. C.; Veldkamp, Marieke W.; Wilders, Ronald

    2012-01-01

    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 Signaling 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 sinoatrial (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 1–1000 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. PMID:22754533

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

    Science.gov (United States)

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

    2014-08-25

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

  10. Monophasic action potentials and activation recovery intervals as measures of ventricular action potential duration: experimental evidence to resolve some controversies

    NARCIS (Netherlands)

    Coronel, Ruben; de Bakker, Jacques M. T.; Wilms-Schopman, Francien J. G.; Opthof, Tobias; Linnenbank, André C.; Belterman, Charly N.; Janse, Michiel J.

    2006-01-01

    BACKGROUND: Activation recovery intervals (ARIs) and monophasic action potential (MAP) duration are used as measures of action potential duration in beating hearts. However, controversies exist concerning the correct way to record MAPs or calculate ARIs. We have addressed these issues

  11. 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.

  12. The electrical potential as a gauge of photosynthetic performance in plant chloroplasts : a patch-clamp study

    NARCIS (Netherlands)

    Voorthuysen, van T.

    1997-01-01

    The earliest events in the energisation of the photosynthetic membrane upon light capture are the formation of a transmembrane electrical potential (AV) and a transmembrane proton gradient (ΔpH). In this thesis ΔΨis employed for the study of the bioenergetics of chloroplast photosynthesis

  13. Teachers in Action Research: Assumptions and Potentials

    Science.gov (United States)

    Li, Yuen-Ling

    2008-01-01

    Research literature has long indicated that action research may stimulate practitioners themselves to actively evaluate the quality of their practice. This study is designed to report the use of action research for the development of early years professional practice by analyzing the pre-project and the post-project video-filmed teaching events.…

  14. 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.

  15. 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

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

    Science.gov (United States)

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

    2013-02-01

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

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

    Science.gov (United States)

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

    2012-10-25

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

  18. Role of action potential configuration and the contribution of C²⁺a and K⁺ currents to isoprenaline-induced changes in canine ventricular cells.

    Science.gov (United States)

    Szentandrássy, N; Farkas, V; Bárándi, L; Hegyi, B; Ruzsnavszky, F; Horváth, B; Bányász, T; Magyar, J; Márton, I; Nánási, P P

    2012-10-01

    Although isoprenaline (ISO) is known to activate several ion currents in mammalian myocardium, little is known about the role of action potential morphology in the ISO-induced changes in ion currents. Therefore, the effects of ISO on action potential configuration, L-type Ca²⁺ current (I(Ca)), slow delayed rectifier K⁺ current (I(Ks)) and fast delayed rectifier K⁺ current (I(Kr)) were studied and compared in a frequency-dependent manner using canine isolated ventricular myocytes from various transmural locations. Action potentials were recorded with conventional sharp microelectrodes; ion currents were measured using conventional and action potential voltage clamp techniques. In myocytes displaying a spike-and-dome action potential configuration (epicardial and midmyocardial cells), ISO caused reversible shortening of action potentials accompanied by elevation of the plateau. ISO-induced action potential shortening was absent in endocardial cells and in myocytes pretreated with 4-aminopyridine. Application of the I(Kr) blocker E-4031 failed to modify the ISO effect, while action potentials were lengthened by ISO in the presence of the I(Ks) blocker HMR-1556. Both action potential shortening and elevation of the plateau were prevented by pretreatment with the I(Ca) blocker nisoldipine. Action potential voltage clamp experiments revealed a prominent slowly inactivating I(Ca) followed by a rise in I(Ks) , both currents increased with increasing the cycle length. The effect of ISO in canine ventricular cells depends critically on action potential configuration, and the ISO-induced activation of I(Ks) - but not I(Kr) - may be responsible for the observed shortening of action potentials. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  19. Role of action potential configuration and the contribution of Ca2+ and K+ currents to isoprenaline-induced changes in canine ventricular cells

    Science.gov (United States)

    Szentandrássy, N; Farkas, V; Bárándi, L; Hegyi, B; Ruzsnavszky, F; Horváth, B; Bányász, T; Magyar, J; Márton, I; Nánási, PP

    2012-01-01

    BACKGROUND AND PURPOSE Although isoprenaline (ISO) is known to activate several ion currents in mammalian myocardium, little is known about the role of action potential morphology in the ISO-induced changes in ion currents. Therefore, the effects of ISO on action potential configuration, L-type Ca2+ current (ICa), slow delayed rectifier K+ current (IKs) and fast delayed rectifier K+ current (IKr) were studied and compared in a frequency-dependent manner using canine isolated ventricular myocytes from various transmural locations. EXPERIMENTAL APPROACH Action potentials were recorded with conventional sharp microelectrodes; ion currents were measured using conventional and action potential voltage clamp techniques. KEY RESULTS In myocytes displaying a spike-and-dome action potential configuration (epicardial and midmyocardial cells), ISO caused reversible shortening of action potentials accompanied by elevation of the plateau. ISO-induced action potential shortening was absent in endocardial cells and in myocytes pretreated with 4-aminopyridine. Application of the IKr blocker E-4031 failed to modify the ISO effect, while action potentials were lengthened by ISO in the presence of the IKs blocker HMR-1556. Both action potential shortening and elevation of the plateau were prevented by pretreatment with the ICa blocker nisoldipine. Action potential voltage clamp experiments revealed a prominent slowly inactivating ICa followed by a rise in IKs, both currents increased with increasing the cycle length. CONCLUSIONS AND IMPLICATIONS The effect of ISO in canine ventricular cells depends critically on action potential configuration, and the ISO-induced activation of IKs– but not IKr– may be responsible for the observed shortening of action potentials. PMID:22563726

  20. Use of the Satinsky clamp for hilar clamping during robotic partial nephrectomy: indications, technique, and multi-center outcomes.

    Science.gov (United States)

    Abdullah, Newaj; Rahbar, Haider; Barod, Ravi; Dalela, Deepansh; Larson, Jeff; Johnson, Michael; Mass, Alon; Zargar, Homayoun; Kaouk, Jihad; Allaf, Mohamad; Bhayani, Sam; Stifelman, Michael; Rogers, Craig

    2017-03-01

    A Satinsky clamp may be a backup option for hilar clamping during robotic partial nephrectomy (RPN) if there are challenges with application of bulldog clamps, but there are potential safety concerns. We evaluate outcomes of RPN using Satinsky vs. bulldog clamps, and provide tips for safe use of the Satinsky as a backup option. Using a multi-center database, we identified 1073 patients who underwent RPN between 2006 and 2013, and had information available about method of hilar clamping (bulldog clamp vs. Satinsky clamp). Patient baseline characteristics, tumor features, and perioperative outcomes were compared between the Satinsky and bulldog clamp groups. A Satinsky clamp was used for hilar clamping in 94 (8.8 %) RPN cases, and bulldog clamps were used in 979 (91.2 %) cases. The use of a Satinsky clamp was associated with greater operative time (198 vs. 175 min, p hilar clamping during challenging RPN cases, but requires careful technique, and was rarely necessary.

  1. 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.

  2. Clamping characteristics study on different types of clamping unit

    Energy Technology Data Exchange (ETDEWEB)

    Jiao, Zhiwei; Liu, Haichao; Xie, Pengcheng [College of Mechanical and Electrical Engineering, Beijing University of Chemical Technology, Beijing China 100029 (China); Yang, Weimin [College of Mechanical and Electrical Engineering, Beijing University of Chemical Technology, Beijing China 100029 (China); State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology, Beijing China 100029 (China)

    2015-05-22

    Plastic products are becoming more and more widely used in aerospace, IT, digital electronics and many other fields. With the development of technology, the requirement of product precision is getting higher and higher. However, type and working performance of clamping unit play a decisive role in product precision. Clamping characteristics of different types of clamping unit are discussed in this article, which use finite element numerical analysis method through the software ABAQUS to study the clamping uniformity, and detect the clamping force repeatability precision. The result shows that compared with toggled three-platen clamping unit, clamping characteristics of internal circulation two-platen clamping unit are better, for instance, its mold cavity deformation and force that bars and mold parting surface suffered are more uniform, and its clamping uniformity and repeatability precision is also better.

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

    Science.gov (United States)

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

    2012-10-25

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

  4. 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.

  5. 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. Copyright © 2010 Elsevier Ltd. All rights reserved.

  6. The human ether-a-go-go-related gene (hERG) current inhibition selectively prolongs action potential of midmyocardial cells to augment transmural dispersion.

    Science.gov (United States)

    Yasuda, C; Yasuda, S; Yamashita, H; Okada, J; Hisada, T; Sugiura, S

    2015-08-01

    The majority of drug induced arrhythmias are related to the prolongation of action potential duration following inhibition of rapidly activating delayed rectifier potassium current (I(Kr)) mediated by the hERG channel. However, for arrhythmias to develop and be sustained, not only the prolongation of action potential duration but also its transmural dispersion are required. Herein, we evaluated the effect of hERG inhibition on transmural dispersion of action potential duration using the action potential clamp technique that combined an in silico myocyte model with the actual I(Kr) measurement. Whole cell I(Kr) current was measured in Chinese hamster ovary cells stably expressing the hERG channel. The measured current was coupled with models of ventricular endocardial, M-, and epicardial cells to calculate the action potentials. Action potentials were evaluated under control condition and in the presence of 1, 10, or 100 μM disopyramide, an hERG inhibitor. Disopyramide dose-dependently increased the action potential durations of the three cell types. However, action potential duration of M-cells increased disproportionately at higher doses, and was significantly different from that of epicardial and endocardial cells (dispersion of repolarization). By contrast, the effects of disopyramide on peak I(Kr) and instantaneous current-voltage relation were similar in all cell types. Simulation study suggested that the reduced repolarization reserve of M-cell with smaller amount of slowly activating delayed rectifier potassium current levels off at longer action potential duration to make such differences. The action potential clamp technique is useful for studying the mechanism of arrhythmogenesis by hERG inhibition through the transmural dispersion of repolarization.

  7. Is action potential threshold lowest in the axon?

    NARCIS (Netherlands)

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

    2008-01-01

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

  8. 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.

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

    Science.gov (United States)

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

    2018-01-01

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

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

    Science.gov (United States)

    Yang, Li-Zhen; Zhu, Yi-Chun

    2015-07-05

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

  11. Selective effects of an octopus toxin on action potentials

    Science.gov (United States)

    Dulhunty, Angela; Gage, Peter W.

    1971-01-01

    1. A lethal, water soluble toxin (Maculotoxin, MTX) with a molecular weight less than 540, can be extracted from the salivary glands of an octopus (Hapalochlaena maculosa). 2. MTX blocks action potentials in sartorius muscle fibres of toads without affecting the membrane potential. Delayed rectification is not inhibited by the toxin. 3. At low concentrations (10-6-10-5 g/ml.) MTX blocks action potentials only after a certain number have been elicited. The number of action potentials, which can be defined accurately, depends on the concentration of MTX and the concentration of sodium ions in the extracellular solution. 4. The toxin has no post-synaptic effect at the neuromuscular junction and it is concluded that it blocks neuromuscular transmission by inhibiting action potentials in motor nerve terminals. PMID:4330930

  12. Storage of energies - Translating potential into actions

    International Nuclear Information System (INIS)

    Signoret, Stephane; Mary, Olivier; Petitot, Pauline; Dejeu, Mathieu; De Santis, Audrey

    2015-01-01

    In this set of articles, a first one evokes issues discussed during a colloquium held in Paris by the European association for storage of energy, the possibilities mentioned about energy storage development in the French bill project for energy transition, and the importance of non-interconnected areas in the development of energy storage. A second article proposes an overview of developments and advances in energy storage in California which adopted suitable laws. The German situation is then briefly described: needs are still to be defined and a road map has been published in 2014, as technologies are expensive and the legal framework is still complex. The next article outlines the conditions of development of the power-to-gas sector (as a process of valorisation of excess electricity). An article gives an overview of technological developments in the field of electrochemical energy storage (batteries). The results of the PEPS study (a study on the potential of energy storage) in Europe are commented. An interview with a member of the French BRGM (Bureau of Mines) outlines the major role which underground storage could play in energy transition. The Seti project for an intelligent thermal energy storage and a better use of renewable energies is then presented. An article comments how to use foodstuff cold to make consumption cut-offs. A last article comments how superconductors could be used in the future for batteries. Few examples are briefly presented: a molten salt-based storage by Areva, a local production of green hydrogen in France, an innovating project of solar energy storage in Switzerland, and the Toucan solar plant in French Guyana

  13. 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

  14. Wireless cardiac action potential transmission with ultrasonically inserted silicon microprobes

    International Nuclear Information System (INIS)

    Shen, C J; Ramkumar, A; Lal, A; Gilmour, R F Jr

    2011-01-01

    This paper reports on the integration of ultrasonically inserted horn-shaped cardiac probes with wireless transmission of 3D cardiac action potential measurement for applications in ex vivo preparations such as monitoring the onset of ventricular fibrillation. Ultrasonically inserted silicon horn probes permit reduced penetration force during insertion, allowing silicon, a brittle material, to penetrate cardiac tissue. The probes also allow recording from multiple sites that are lithographically defined. An application-specific integrated circuit has been designed with a 40 dB amplifying stage and a frequency modulating oscillator at 95 MHz to wirelessly transmit the recorded action potentials. This ultrasonically inserted microprobe wireless system demonstrates the initial results in wireless monitoring of 3D action potential propagation, and the extraction of parameters of interest including the action potential duration and diastolic interval

  15. Fiber Optic Detection of Action Potentials in Axons

    National Research Council Canada - National Science Library

    Smela, Elisabeth

    2006-01-01

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

  16. 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......Nerve impulse, also called action potential, has mostly been considered as a pure electrical phenomenon. However, changes in dimensions, e.g. thickness and length, and in temperature along with action potentials have been observed, which indicates that the nerve is a thermodynamic system. The work...

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

    Science.gov (United States)

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

    2015-01-01

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

  18. Components of action potential repolarization in cerebellar parallel fibres.

    Science.gov (United States)

    Pekala, Dobromila; Baginskas, Armantas; Szkudlarek, Hanna J; Raastad, Morten

    2014-11-15

    Repolarization of the presynaptic action potential is essential for transmitter release, excitability and energy expenditure. Little is known about repolarization in thin, unmyelinated axons forming en passant synapses, which represent the most common type of axons in the mammalian brain's grey matter.We used rat cerebellar parallel fibres, an example of typical grey matter axons, to investigate the effects of K(+) channel blockers on repolarization. We show that repolarization is composed of a fast tetraethylammonium (TEA)-sensitive component, determining the width and amplitude of the spike, and a slow margatoxin (MgTX)-sensitive depolarized after-potential (DAP). These two components could be recorded at the granule cell soma as antidromic action potentials and from the axons with a newly developed miniaturized grease-gap method. A considerable proportion of fast repolarization remained in the presence of TEA, MgTX, or both. This residual was abolished by the addition of quinine. The importance of proper control of fast repolarization was demonstrated by somatic recordings of antidromic action potentials. In these experiments, the relatively broad K(+) channel blocker 4-aminopyridine reduced the fast repolarization, resulting in bursts of action potentials forming on top of the DAP. We conclude that repolarization of the action potential in parallel fibres is supported by at least three groups of K(+) channels. Differences in their temporal profiles allow relatively independent control of the spike and the DAP, whereas overlap of their temporal profiles provides robust control of axonal bursting properties.

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

    DEFF Research Database (Denmark)

    Krarup, Christian

    2004-01-01

    The compound sensory nerve action potential (SNAP) is the result of phase summation and cancellation of single fiber potentials (SFAPs) with amplitudes that depend on fiber diameter, and the amplitude and shape of the SNAP is determined by the distribution of fiber diameters. Conduction velocitie...... effort and attention to theory and practical detail that may be time consuming....

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

    Science.gov (United States)

    Syren, R. M.; Fox, S. W.; Przybylski, A. T.; Stratten, W. P.

    1982-01-01

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

  1. Numerical investigation of action potential transmission in plants

    Directory of Open Access Journals (Sweden)

    Mariusz Pietruszka

    2014-01-01

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

  2. Kv2 Channel Regulation of Action Potential Repolarization and Firing Patterns in Superior Cervical Ganglion Neurons and Hippocampal CA1 Pyramidal Neurons

    Science.gov (United States)

    Liu, Pin W.

    2014-01-01

    Kv2 family “delayed-rectifier” potassium channels are widely expressed in mammalian neurons. Kv2 channels activate relatively slowly and their contribution to action potential repolarization under physiological conditions has been unclear. We explored the function of Kv2 channels using a Kv2-selective blocker, Guangxitoxin-1E (GxTX-1E). Using acutely isolated neurons, mixed voltage-clamp and current-clamp experiments were done at 37°C to study the physiological kinetics of channel gating and action potentials. In both rat superior cervical ganglion (SCG) neurons and mouse hippocampal CA1 pyramidal neurons, 100 nm GxTX-1E produced near-saturating block of a component of current typically constituting ∼60–80% of the total delayed-rectifier current. GxTX-1E also reduced A-type potassium current (IA), but much more weakly. In SCG neurons, 100 nm GxTX-1E broadened spikes and voltage clamp experiments using action potential waveforms showed that Kv2 channels carry ∼55% of the total outward current during action potential repolarization despite activating relatively late in the spike. In CA1 neurons, 100 nm GxTX-1E broadened spikes evoked from −70 mV, but not −80 mV, likely reflecting a greater role of Kv2 when other potassium channels were partially inactivated at −70 mV. In both CA1 and SCG neurons, inhibition of Kv2 channels produced dramatic depolarization of interspike voltages during repetitive firing. In CA1 neurons and some SCG neurons, this was associated with increased initial firing frequency. In all neurons, inhibition of Kv2 channels depressed maintained firing because neurons entered depolarization block more readily. Therefore, Kv2 channels can either decrease or increase neuronal excitability depending on the time scale of excitation. PMID:24695716

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

    DEFF Research Database (Denmark)

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

    2006-01-01

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

  4. Activation of Mechanosensitive Transient Receptor Potential/Piezo Channels in Odontoblasts Generates Action Potentials in Cocultured Isolectin B4-negative Medium-sized Trigeminal Ganglion Neurons.

    Science.gov (United States)

    Sato, Masaki; Ogura, Kazuhiro; Kimura, Maki; Nishi, Koichi; Ando, Masayuki; Tazaki, Masakazu; Shibukawa, Yoshiyuki

    2018-04-27

    Various stimuli to the dentin surface elicit dentinal pain by inducing dentinal fluid movement causing cellular deformation in odontoblasts. Although odontoblasts detect deformation by the activation of mechanosensitive ionic channels, it is still unclear whether odontoblasts are capable of establishing neurotransmission with myelinated A delta (Aδ) neurons. Additionally, it is still unclear whether these neurons evoke action potentials by neurotransmitters from odontoblasts to mediate sensory transduction in dentin. Thus, we investigated evoked inward currents and evoked action potentials form trigeminal ganglion (TG) neurons after odontoblast mechanical stimulation. We used patch clamp recordings to identify electrophysiological properties and record evoked responses in TG neurons. We classified TG cells into small-sized and medium-sized neurons. In both types of neurons, we observed voltage-dependent inward currents. The currents from medium-sized neurons showed fast inactivation kinetics. When mechanical stimuli were applied to odontoblasts, evoked inward currents were recorded from medium-sized neurons. Antagonists for the ionotropic adenosine triphosphate receptor (P2X 3 ), transient receptor potential channel subfamilies, and Piezo1 channel significantly inhibited these inward currents. Mechanical stimulation to odontoblasts also generated action potentials in the isolectin B 4 -negative medium-sized neurons. Action potentials in these isolectin B 4 -negative medium-sized neurons showed a short duration. Overall, electrophysiological properties of neurons indicate that the TG neurons with recorded evoked responses after odontoblast mechanical stimulation were myelinated Aδ neurons. Odontoblasts established neurotransmission with myelinated Aδ neurons via P2X 3 receptor activation. The results also indicated that mechanosensitive TRP/Piezo1 channels were functionally expressed in odontoblasts. The activation of P2X 3 receptors induced an action potential

  5. Arsenic Trioxide Modulates the Central Snail Neuron Action Potential

    Directory of Open Access Journals (Sweden)

    Guan-Ling Lu

    2009-09-01

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

  6. β1-Adrenoceptor autoantibodies affect action potential duration and delayed rectifier potassium currents in guinea pigs.

    Science.gov (United States)

    Zhao, Yuhui; Huang, Haixia; Du, Yunhui; Li, Xiao; Lv, Tingting; Zhang, Suli; Wei, Hua; Shang, Jianyu; Liu, Ping; Liu, Huirong

    2015-01-01

    β1-Adrenoceptor autoantibodies (β1-AAs) affect the action potential duration (APD) in cardiomyocytes and are related to ventricular arrhythmias. The delayed rectifier potassium current (I K) plays a crucial role in APD, but the effects of β1-AAs on I K have not been completely illuminated. This work aimed to observe the effects of β1-AAs on I K and APD and further explore the mechanisms of β1-AA-mediated ventricular arrhythmias. β1-AAs were obtained from sera of patients with coronary heart disease (CHD) and nonsustained ventricular tachycardia. With whole-cell patch clamp technique, action potentials and I K were recorded. The results illustrated 0.1 μmol/L β1-AAs shortened APD at 50 % (APD50) and 90 % (APD90) of the repolarization. However, at 0.01 μmol/L, β1-AAs had no effects on either APD90 or APD50 (P > 0.05). At 0.001 μmol/L, β1-AAs significantly prolonged APD90 and APD50. Moreover, β1-AAs (0.001, 0.01, 0.1 μmol/L) dose-dependently increased the rapidly activating delayed rectifier potassium current (I Kr), but similarly decreased the slowly activating delayed rectifier potassium current (I Ks) and increased L-type calcium currents at the different concentrations. Taken together, the IKr increase induced by high β1-AA concentrations is responsible for a significant APD reduction which would contribute to repolarization changes and trigger the malignant ventricular arrhythmias in CHD patients.

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

    Science.gov (United States)

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

    2013-08-01

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

  8. Planar patch clamp: advances in electrophysiology.

    Science.gov (United States)

    Brüggemann, Andrea; Farre, Cecilia; Haarmann, Claudia; Haythornthwaite, Ali; Kreir, Mohamed; Stoelzle, Sonja; George, Michael; Fertig, Niels

    2008-01-01

    Ion channels have gained increased interest as therapeutic targets over recent years, since a growing number of human and animal diseases have been attributed to defects in ion channel function. Potassium channels are the largest and most diverse family of ion channels. Pharmaceutical agents such as Glibenclamide, an inhibitor of K(ATP) channel activity which promotes insulin release, have been successfully sold on the market for many years. So far, only a small group of the known ion channels have been addressed as potential drug targets. The functional testing of drugs on these ion channels has always been the bottleneck in the development of these types of pharmaceutical compounds.New generations of automated patch clamp screening platforms allow a higher throughput for drug testing and widen this bottleneck. Due to their planar chip design not only is a higher throughput achieved, but new applications have also become possible. One of the advantages of planar patch clamp is the possibility of perfusing the intracellular side of the membrane during a patch clamp experiment in the whole-cell configuration. Furthermore, the extracellular membrane remains accessible for compound application during the experiment.Internal perfusion can be used not only for patch clamp experiments with cell membranes, but also for those with artificial lipid bilayers. In this chapter we describe how internal perfusion can be applied to potassium channels expressed in Jurkat cells, and to Gramicidin channels reconstituted in a lipid bilayer.

  9. Increased transient Na+ conductance and action potential output in layer 2/3 prefrontal cortex neurons of the fmr1-/y mouse.

    Science.gov (United States)

    Routh, Brandy N; Rathour, Rahul K; Baumgardner, Michael E; Kalmbach, Brian E; Johnston, Daniel; Brager, Darrin H

    2017-07-01

    Layer 2/3 neurons of the prefrontal cortex display higher gain of somatic excitability, responding with a higher number of action potentials for a given stimulus, in fmr1 -/y mice. In fmr1 -/y L2/3 neurons, action potentials are taller, faster and narrower. Outside-out patch clamp recordings revealed that the maximum Na + conductance density is higher in fmr1 -/y L2/3 neurons. Measurements of three biophysically distinct K + currents revealed a depolarizing shift in the activation of a rapidly inactivating (A-type) K + conductance. Realistic neuronal simulations of the biophysical observations recapitulated the elevated action potential and repetitive firing phenotype. Fragile X syndrome is the most common form of inherited mental impairment and autism. The prefrontal cortex is responsible for higher order cognitive processing, and prefrontal dysfunction is believed to underlie many of the cognitive and behavioural phenotypes associated with fragile X syndrome. We recently demonstrated that somatic and dendritic excitability of layer (L) 5 pyramidal neurons in the prefrontal cortex of the fmr1 -/y mouse is significantly altered due to changes in several voltage-gated ion channels. In addition to L5 pyramidal neurons, L2/3 pyramidal neurons play an important role in prefrontal circuitry, integrating inputs from both lower brain regions and the contralateral cortex. Using whole-cell current clamp recording, we found that L2/3 pyramidal neurons in prefrontal cortex of fmr1 -/y mouse fired more action potentials for a given stimulus compared with wild-type neurons. In addition, action potentials in fmr1 -/y neurons were significantly larger, faster and narrower. Voltage clamp of outside-out patches from L2/3 neurons revealed that the transient Na + current was significantly larger in fmr1 -/y neurons. Furthermore, the activation curve of somatic A-type K + current was depolarized. Realistic conductance-based simulations revealed that these biophysical changes in Na

  10. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Modelling in vivo action potential propagation along a giant axon.

    Science.gov (United States)

    George, Stuart; Foster, Jamie M; Richardson, Giles

    2015-01-01

    A partial differential equation model for the three-dimensional current flow in an excitable, unmyelinated axon is considered. Where the axon radius is significantly below a critical value R(crit) (that depends upon intra- and extra-cellular conductivity and ion channel conductance) the resistance of the intracellular space is significantly higher than that of the extracellular space, such that the potential outside the axon is uniformly small whilst the intracellular potential is approximated by the transmembrane potential. In turn, since the current flow is predominantly axial, it can be shown that the transmembrane potential is approximated by a solution to the one-dimensional cable equation. It is noted that the radius of the squid giant axon, investigated by (Hodgkin and Huxley 1952e), lies close to R(crit). This motivates us to apply the three-dimensional model to the squid giant axon and compare the results thus found to those obtained using the cable equation. In the context of the in vitro experiments conducted in (Hodgkin and Huxley 1952e) we find only a small difference between the wave profiles determined using these two different approaches and little difference between the speeds of action potential propagation predicted. This suggests that the cable equation approximation is accurate in this scenario. However when applied to the it in vivo setting, in which the conductivity of the surrounding tissue is considerably lower than that of the axoplasm, there are marked differences in both wave profile and speed of action potential propagation calculated using the two approaches. In particular, the cable equation significantly over predicts the increase in the velocity of propagation as axon radius increases. The consequences of these results are discussed in terms of the evolutionary costs associated with increasing the speed of action potential propagation by increasing axon radius.

  12. Automated patch clamp on mESC-derived cardiomyocytes for cardiotoxicity prediction.

    Science.gov (United States)

    Stoelzle, Sonja; Haythornthwaite, Alison; Kettenhofen, Ralf; Kolossov, Eugen; Bohlen, Heribert; George, Michael; Brüggemann, Andrea; Fertig, Niels

    2011-09-01

    Cardiovascular side effects are critical in drug development and have frequently led to late-stage project terminations or even drug withdrawal from the market. Physiologically relevant and predictive assays for cardiotoxicity are hence strongly demanded by the pharmaceutical industry. To identify a potential impact of test compounds on ventricular repolarization, typically a variety of ion channels in diverse heterologously expressing cells have to be investigated. Similar to primary cells, in vitro-generated stem cell-derived cardiomyocytes simultaneously express cardiac ion channels. Thus, they more accurately represent the native situation compared with cell lines overexpressing only a single type of ion channel. The aim of this study was to determine if stem cell-derived cardiomyocytes are suited for use in an automated patch clamp system. The authors show recordings of cardiac ion currents as well as action potential recordings in readily available stem cell-derived cardiomyocytes. Besides monitoring inhibitory effects of reference compounds on typical cardiac ion currents, the authors revealed for the first time drug-induced modulation of cardiac action potentials in an automated patch clamp system. The combination of an in vitro cardiac cell model with higher throughput patch clamp screening technology allows for a cost-effective cardiotoxicity prediction in a physiologically relevant cell system.

  13. Warm Body Temperature Facilitates Energy Efficient Cortical Action Potentials

    Science.gov (United States)

    Yu, Yuguo; Hill, Adam P.; McCormick, David A.

    2012-01-01

    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. PMID:22511855

  14. 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.

  15. Heteromeric Kv7.2/7.3 channels differentially regulate action potential initiation and conduction in neocortical myelinated axons.

    Science.gov (United States)

    Battefeld, Arne; Tran, Baouyen T; Gavrilis, Jason; Cooper, Edward C; Kole, Maarten H P

    2014-03-05

    Rapid energy-efficient signaling along vertebrate axons is achieved through intricate subcellular arrangements of voltage-gated ion channels and myelination. One recently appreciated example is the tight colocalization of K(v)7 potassium channels and voltage-gated sodium (Na(v)) channels in the axonal initial segment and nodes of Ranvier. The local biophysical properties of these K(v)7 channels and the functional impact of colocalization with Na(v) channels remain poorly understood. Here, we quantitatively examined K(v)7 channels in myelinated axons of rat neocortical pyramidal neurons using high-resolution confocal imaging and patch-clamp recording. K(v)7.2 and 7.3 immunoreactivity steeply increased within the distal two-thirds of the axon initial segment and was mirrored by the conductance density estimates, which increased from ~12 (proximal) to 150 pS μm(-2) (distal). The axonal initial segment and nodal M-currents were similar in voltage dependence and kinetics, carried by K(v)7.2/7.3 heterotetramers, 4% activated at the resting membrane potential and rapidly activated with single-exponential time constants (~15 ms at 28 mV). Experiments and computational modeling showed that while somatodendritic K(v)7 channels are strongly activated by the backpropagating action potential to attenuate the afterdepolarization and repetitive firing, axonal K(v)7 channels are minimally recruited by the forward-propagating action potential. Instead, in nodal domains K(v)7.2/7.3 channels were found to increase Na(v) channel availability and action potential amplitude by stabilizing the resting membrane potential. Thus, K(v)7 clustering near axonal Na(v) channels serves specific and context-dependent roles, both restraining initiation and enhancing conduction of the action potential.

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2015-11-25

    The role of interneurons in cortical microcircuits is strongly influenced by their passive and active electrical properties. Although different types of interneurons exhibit unique electrophysiological properties recorded at the soma, it is not yet clear whether these differences are also manifested in other neuronal compartments. To address this question, we have used voltage-sensitive dye to image the propagation of action potentials into the fine collaterals of axons and dendrites in two of the largest cortical interneuron subtypes in the mouse: fast-spiking interneurons, which are typically basket or chandelier neurons; and somatostatin containing interneurons, which are typically regular spiking Martinotti cells. We found that fast-spiking and somatostatin-expressing interneurons differed in their electrophysiological characteristics along their entire dendrosomatoaxonal extent. The action potentials generated in the somata and axons, including axon collaterals, of somatostatin-expressing interneurons are significantly broader than those generated in the same compartments of fast-spiking inhibitory interneurons. In addition, action potentials back-propagated into the dendrites of somatostatin-expressing interneurons much more readily than fast-spiking interneurons. Pharmacological investigations suggested that axonal action potential repolarization in both cell types depends critically upon Kv1 channels, whereas the axonal and somatic action potentials of somatostatin-expressing interneurons also depend on BK Ca(2+)-activated K(+) channels. These results indicate that the two broad classes of interneurons studied here have expressly different subcellular physiological properties, allowing them to perform unique computational roles in cortical circuit operations. Neurons in the cerebral cortex are of two major types: excitatory and inhibitory. The proper balance of excitation and inhibition in the brain is critical for its operation. Neurons contain three main

  18. Implementing participatory action research in Lithuania: potential and challenges

    Directory of Open Access Journals (Sweden)

    Gabija Jarašiūnaitė

    2015-12-01

    Full Text Available Participatory action research is a quite new approach to research in Lithuania. The aim of an article was to disscuss the potential and challenges of participatory action research while implementing it in Lithuanian organizations. The qualitative approach was chosen for the study using the method of Focus groups. 20 researchers from social and biomedicine sciences from six institutions of High education in Lithuania participated in the study. The results of the study showed that participatory action reasearch is seen as an approach with many possibilities because of a wide range of used methods, constant interactions with research participants and the lenght of the research process. Researchers value the possibility to access organization at the begining, during research process and evaluate the effectiveness of the changes after the process. The research challenges are associated with the competence of a researcher including his/her sensitivity during process, ability to involve active participation of organization members in the ongoing process by creating safe and trusting environment. Some specific challenges associated with Lithuanian organizations are organizations‘ tiredness of researches and lack of faith of the benefits of researches because of some previous experiences. Keywords: Participatory Action Research, Organization, Lithuania.

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

    Directory of Open Access Journals (Sweden)

    F Woodward Hopf

    2013-04-01

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

  20. Voltage clamp methods for the study of membrane currents and SR Ca2+ release in adult skeletal muscle fibres

    Science.gov (United States)

    Hernández-Ochoa, Erick O.; Schneider, Martin F.

    2012-01-01

    Skeletal muscle excitation-contraction (E-C)1 coupling is a process composed of multiple sequential stages, by which an action potential triggers sarcoplasmic reticulum (SR)2 Ca2+ release and subsequent contractile activation. The various steps in the E-C coupling process in skeletal muscle can be studied using different techniques. The simultaneous recordings of sarcolemmal electrical signals and the accompanying elevation in myoplasmic Ca2+, due to depolarization-initiated SR Ca2+ release in skeletal muscle fibres, have been useful to obtain a better understanding of muscle function. In studying the origin and mechanism of voltage dependency of E-C coupling a variety of different techniques have been used to control the voltage in adult skeletal fibres. Pioneering work in muscles isolated from amphibians or crustaceans used microelectrodes or ‘high resistance gap’ techniques to manipulate the voltage in the muscle fibres. The development of the patch clamp technique and its variant, the whole-cell clamp configuration that facilitates the manipulation of the intracellular environment, allowed the use of the voltage clamp techniques in different cell types, including skeletal muscle fibres. The aim of this article is to present an historical perspective of the voltage clamp methods used to study skeletal muscle E-C coupling as well as to describe the current status of using the whole-cell patch clamp technique in studies in which the electrical and Ca2+ signalling properties of mouse skeletal muscle membranes are being investigated. PMID:22306655

  1. 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...... dispersion over increasing conduction distance is greater for the SNAP than CMAP, and demonstration of conduction block is therefore difficult. In addition, the effect of temporal dispersion on amplitude and shape is strongly dependent on the number of conducting fibers and their distribution, and......, 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...

  2. Surface deformation during an action potential in pearled cells

    Science.gov (United States)

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

    2017-11-01

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

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

    KAUST Repository

    Keener, James P.; Newby, Jay M.

    2011-01-01

    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

  4. Action Potential Broadening in Capsaicin-Sensitive DRG Neurons from Frequency-Dependent Reduction of Kv3 Current.

    Science.gov (United States)

    Liu, Pin W; Blair, Nathaniel T; Bean, Bruce P

    2017-10-04

    Action potential (AP) shape is a key determinant of cellular electrophysiological behavior. We found that in small-diameter, capsaicin-sensitive dorsal root ganglia neurons corresponding to nociceptors (from rats of either sex), stimulation at frequencies as low as 1 Hz produced progressive broadening of the APs. Stimulation at 10 Hz for 3 s resulted in an increase in AP width by an average of 76 ± 7% at 22°C and by 38 ± 3% at 35°C. AP clamp experiments showed that spike broadening results from frequency-dependent reduction of potassium current during spike repolarization. The major current responsible for frequency-dependent reduction of overall spike-repolarizing potassium current was identified as Kv3 current by its sensitivity to low concentrations of 4-aminopyridine (IC 50 action potentials of small-diameter rat DRG neurons showed spike broadening at frequencies as low as 1 Hz and that spike broadening resulted predominantly from frequency-dependent inactivation of Kv3 channels. Spike width helps to control transmitter release, conduction velocity, and firing patterns and understanding the role of particular potassium channels can help to guide new pharmacological strategies for targeting pain-sensing neurons selectively. Copyright © 2017 the authors 0270-6474/17/379705-10$15.00/0.

  5. The Potential of Deweyan-Inspired Action Research

    Science.gov (United States)

    Stark, Jody L.

    2014-01-01

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

  6. Clamp wins pipe repair prize

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    2001-04-01

    This paper describes the permanent pipeline repair system, developed by Tekmar, which is powered by seawater hydraulics and is easily installed and tested by any workclass remotely operated vehicle (rov). Details are given of the two main components of the system, namely, the diverless high pressure split repair clamp and the rov-operated tool to install it.

  7. Map-based model of the cardiac action potential

    International Nuclear Information System (INIS)

    Pavlov, Evgeny A.; Osipov, Grigory V.; Chan, C.K.; Suykens, Johan A.K.

    2011-01-01

    A simple computationally efficient model which is capable of replicating the basic features of cardiac cell action potential is proposed. The model is a four-dimensional map and demonstrates good correspondence with real cardiac cells. Various regimes of cardiac activity, which can be reproduced by the proposed model, are shown. Bifurcation mechanisms of these regimes transitions are explained using phase space analysis. The dynamics of 1D and 2D lattices of coupled maps which model the behavior of electrically connected cells is discussed in the context of synchronization theory. -- Highlights: → Recent experimental-data based models are complicated for analysis and simulation. → The simplified map-based model of the cardiac cell is constructed. → The model is capable for replication of different types of cardiac activity. → The spatio-temporal dynamics of ensembles of coupled maps are investigated. → Received data are analyzed in context of biophysical processes in the myocardium.

  8. Map-based model of the cardiac action potential

    Energy Technology Data Exchange (ETDEWEB)

    Pavlov, Evgeny A., E-mail: genie.pavlov@gmail.com [Department of Computational Mathematics and Cybernetics, Nizhny Novgorod State University, 23, Gagarin Avenue, 603950 Nizhny Novgorod (Russian Federation); Osipov, Grigory V. [Department of Computational Mathematics and Cybernetics, Nizhny Novgorod State University, 23, Gagarin Avenue, 603950 Nizhny Novgorod (Russian Federation); Chan, C.K. [Institute of Physics, Academia Sinica, 128 Sec. 2, Academia Road, Nankang, Taipei 115, Taiwan (China); Suykens, Johan A.K. [K.U. Leuven, ESAT-SCD/SISTA, Kasteelpark Arenberg 10, B-3001 Leuven (Heverlee) (Belgium)

    2011-07-25

    A simple computationally efficient model which is capable of replicating the basic features of cardiac cell action potential is proposed. The model is a four-dimensional map and demonstrates good correspondence with real cardiac cells. Various regimes of cardiac activity, which can be reproduced by the proposed model, are shown. Bifurcation mechanisms of these regimes transitions are explained using phase space analysis. The dynamics of 1D and 2D lattices of coupled maps which model the behavior of electrically connected cells is discussed in the context of synchronization theory. -- Highlights: → Recent experimental-data based models are complicated for analysis and simulation. → The simplified map-based model of the cardiac cell is constructed. → The model is capable for replication of different types of cardiac activity. → The spatio-temporal dynamics of ensembles of coupled maps are investigated. → Received data are analyzed in context of biophysical processes in the myocardium.

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

    Science.gov (United States)

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

    2018-03-01

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

  10. Multifrequency Excitation of a Clamped-Clamped Microbeam

    KAUST Repository

    Jaber, Nizar R.

    2016-01-20

    We present analytical and experimental investigation of an electrically actuated clamped-clamped microbeam under a twosource harmonic excitation. The first frequency is swept around the first mode of vibration where the second one is fixed. These microbeams are fabricated using polyimide as structural layer coated with nickel form top and chromium and gold layers from bottom. We demonstrate the excitation of additive and subtractive type resonance. We show that by properly tuning the frequency and the amplitude of the excitation force, the frequency bandwidth of the resonator is increased. Theoretically, we solved the eigenvalue problem for different axial forces to find the natural frequencies ratio that match the experimental values. Using Galerkin method, a reduced order model is derived to simulate the static and dynamic response of the device where using three symmetric mode shapes provided a good agreement with experimental data. © Copyright 2015 by ASME.

  11. 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.

  12. Short latency compound action potentials from mammalian gravity receptor organs

    Science.gov (United States)

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

    1999-01-01

    Gravity receptor function was characterized in four mammalian species using far-field vestibular evoked potentials (VsEPs). VsEPs are compound action potentials of the vestibular nerve and central relays that are elicited by linear acceleration ramps applied to the cranium. Rats, mice, guinea pigs, and gerbils were studied. In all species, response onset occurred within 1.5 ms of the stimulus onset. Responses persisted during intense (116 dBSPL) wide-band (50 to 50 inverted question mark omitted inverted question mark000 Hz) forward masking, whereas auditory responses to intense clicks (112 dBpeSPL) were eliminated under the same conditions. VsEPs remained after cochlear extirpation but were eliminated following bilateral labyrinthectomy. Responses included a series of positive and negative peaks that occurred within 8 ms of stimulus onset (range of means at +6 dBre: 1.0 g/ms: P1=908 to 1062 micros, N1=1342 to 1475 micros, P2=1632 to 1952 micros, N2=2038 to 2387 micros). Mean response amplitudes at +6 dBre: 1.0 g/ms ranged from 0.14 to 0.99 microV. VsEP input/output functions revealed latency slopes that varied across peaks and species ranging from -19 to -51 micros/dB. Amplitude-intensity slopes also varied ranging from 0.04 to 0.08 microV/dB for rats and mice. Latency values were comparable to those of birds although amplitudes were substantially smaller in mammals. VsEP threshold values were considerably higher in mammals compared to birds and ranged from -8.1 to -10.5 dBre 1.0 g/ms across species. These results support the hypothesis that mammalian gravity receptors are less sensitive to dynamic stimuli than are those of birds.

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

    Science.gov (United States)

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

    2012-06-03

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

  14. Loading dynamics of a sliding DNA clamp.

    KAUST Repository

    Cho, Won-Ki

    2014-05-22

    Sliding DNA clamps are loaded at a ss/dsDNA junction by a clamp loader that depends on ATP binding for clamp opening. Sequential ATP hydrolysis results in closure of the clamp so that it completely encircles and diffuses on dsDNA. We followed events during loading of an E. coli β clamp in real time by using single-molecule FRET (smFRET). Three successive FRET states were retained for 0.3 s, 0.7 s, and 9 min: Hydrolysis of the first ATP molecule by the γ clamp loader resulted in closure of the clamp in 0.3 s, and after 0.7 s in the closed conformation, the clamp was released to diffuse on the dsDNA for at least 9 min. An additional single-molecule polarization study revealed that the interfacial domain of the clamp rotated in plane by approximately 8° during clamp closure. The single-molecule polarization and FRET studies thus revealed the real-time dynamics of the ATP-hydrolysis-dependent 3D conformational change of the β clamp during loading at a ss/dsDNA junction.

  15. Is early cord clamping, delayed cord clamping or cord milking best?

    Science.gov (United States)

    Vatansever, Binay; Demirel, Gamze; Ciler Eren, Elif; Erel, Ozcan; Neselioglu, Salim; Karavar, Hande Nur; Gundogdu, Semra; Ulfer, Gozde; Bahadir, Selcen; Tastekin, Ayhan

    2018-04-01

    To compare the antioxidant status of three cord clamping procedures (early clamping, delayed clamping and milking) by analyzing the thiol-disulfide balance. This randomized controlled study enrolled 189 term infants who were divided into three groups according to the cord clamping procedure: early clamping, delayed clamping and milking. Blood samples were collected from the umbilical arteries immediately after clamping, and the thiol/disulfide homeostasis was analyzed. The native and total thiol levels were significantly (p total thiol ratio was significantly (p = .026) lower in the delayed cord clamping and milking groups compared with the early clamping groups. Early cord clamping causes the production of more disulfide bonds and lower thiol levels, indicating that oxidation reactions are increased in the early cord clamping procedure compared with the delayed cord clamping and milking procedures. The oxidant capacity is greater with early cord clamping than with delayed clamping or cord milking. Delayed cord clamping or milking are beneficial in neonatal care, and we suggest that they be performed routinely in all deliveries.

  16. Multiple Actions of Rotenone, an Inhibitor of Mitochondrial Respiratory Chain, on Ionic Currents and Miniature End-Plate Potential in Mouse Hippocampal (mHippoE-14 Neurons

    Directory of Open Access Journals (Sweden)

    Chin-Wei Huang

    2018-05-01

    Full Text Available Background/Aims: Rotenone (Rot is known to suppress the activity of complex I in the mitochondrial chain reaction; however, whether this compound has effects on ion currents in neurons remains largely unexplored. Methods: With the aid of patch-clamp technology and simulation modeling, the effects of Rot on membrane ion currents present in mHippoE-14 cells were investigated. Results: Addition of Rot produced an inhibitory action on the peak amplitude of INa with an IC50 value of 39.3 µM; however, neither activation nor inactivation kinetics of INa was changed during cell exposure to this compound. Addition of Rot produced little or no modifications in the steady-state inactivation curve of INa. Rot increased the amplitude of Ca2+-activated Cl- current in response to membrane depolarization with an EC50 value of 35.4 µM; further addition of niflumic acid reversed Rot-mediated stimulation of this current. Moreover, when these cells were exposed to 10 µM Rot, a specific population of ATP-sensitive K+ channels with a single-channel conductance of 18.1 pS was measured, despite its inability to alter single-channel conductance. Under current clamp condition, the frequency of miniature end-plate potentials in mHippoE-14 cells was significantly raised in the presence of Rot (10 µM with no changes in their amplitude and time course of rise and decay. In simulated model of hippocampal neurons incorporated with chemical autaptic connection, increased autaptic strength to mimic the action of Rot was noted to change the bursting pattern with emergence of subthreshold potentials. Conclusions: The Rot effects presented herein might exert a significant action on functional activities of hippocampal neurons occurring in vivo.

  17. Identification of motivations for unsafe driving actions and potential countermeasures

    Science.gov (United States)

    1982-03-01

    This report presents the findings of a preliminary investigation of drivers' motivations for selected unsafe driving actions (UDAs). The general objective of the study was to develop the test methods, procedures, and materials for collecting data for...

  18. 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.

  19. 76 FR 21938 - Potential Environmental Impacts of the Proposed Runway 13 Extension and Associated Actions for...

    Science.gov (United States)

    2011-04-19

    ... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Potential Environmental Impacts of the Proposed Runway 13 Extension and Associated Actions for the Devils Lake Regional Airport in Devils Lake, ND AGENCY: Federal Aviation Administration (FAA), Department of Transportation (DOT). ACTION...

  20. 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.

  1. Scaling of the quark-antiquark potential and improved actions in SU(2) lattice gauge theory

    International Nuclear Information System (INIS)

    Montvay, I.; Gutbrod, F.

    1983-11-01

    The scaling behaviour of the quark-antiquark potential is investigated by a high statistics Monte Carlo calculation in SU(2) lattice gauge theory. Besides the standard one-plaquette action we also use Symanzik's tree-level improved action and Wilson's block-spin improved action. No significant differences between Symanzik's action and the standard action have been observed. For small β Wilson's action scales differently. The string tension value chi extracted from the data corresponds to Λsub(latt) = (0.018 +- 0.001) √chi for the one-plaquette action. (orig.)

  2. Analysis list: Clamp [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Clamp Cell line + dm3 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/target/Clamp.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/target/Clam...p.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/target/Clam...p.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/colo/Clamp.Cell_line.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/colo/Cell_line.gml ...

  3. 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,…

  4. [Phenibut potentiation of the therapeutic action of antiparkinson agents].

    Science.gov (United States)

    Gol'dblat, Iu V; Lapin, I P

    1986-01-01

    It was observed in experiments on mice that the central action of phenibut (beta-phenyl-gamma-aminobutyric acid) diminished after destruction of brain dopaminergic neurons by 6-hydroxydopamine and after pretreatment with the dopamine receptor blocker haloperidol which suggests the dopaminergic component in the action of phenibut. In 13 of 16 patients receiving long-term treatment with antiparkinsonic drugs, addition of phenibut (0.25 g thrice daily for 10 days) resulted in marked clinical improvement with a significant increase of motor activity, as well as diminution of both rigidity and tremor. Follow-up showed a significant lowering of muscle tone of rigid muscles, augmentation of their strength and amplitude of movements. In 8 patients receiving phenibut without antiparkinsonic drugs the results were negligible.

  5. 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......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...

  6. Theoretical and experimental nonlinear dynamics of a clamped-clamped beam MEMS resonator

    NARCIS (Netherlands)

    Mestrom, R.M.C.; Fey, R.H.B.; Nijmeijer, H.

    2008-01-01

    Microelectromechanical resonators feature nonlineardynamic responses. A first-principles based modeling approach is proposed for a clamped-clamped beam resonator. Starting from the partial differential equation for the beam including geometric and electrostatic nonlinear effects, a reduced-order

  7. COMPARISON OF EARLY AND DELAYED UMBILICAL CORD CLAMPING IN THE THIRD STAGE OF LABOUR

    Directory of Open Access Journals (Sweden)

    Tamara Serdinšek

    2015-09-01

    Full Text Available Background: Umbilical cord clamping in the third stage of labour is still controversial. Early cord clamping is defined as clamping at 10, 15, 30 or 60 seconds after delivery and delayed as clamping after 60 seconds or at 2-5 minutes after delivery, when the cord stops pulsating or when the placenta is visible within the birth canal. Early clamping is one of the three components of active management of the third stage of labour, which has been used widely in modern obstetrics during the last century. However, in some northern European countries, various parts of the USA and Canada and in developing countries physiological management is preferred.Conclusions: After publication of several trials describing advantages of delayed clamping, this has recently been progressively replacing early clamping. The most important advantages of delayed cord clamping are higher haemoglobin and ferritin levels, higher iron stores, lower incidence of iron deficiency anaemia, better cardiopulmonary adaptation, lower rate of respiratory distress syndrome, and longer duration of early breastfeeding in term neonates, while there is no increase in the incidence of postpartum haemorrhage. Delayed clamping seems to bring some advantages for preterm neonates as well. However, caution is still advised because of the potential adverse effects, especially polycythaemia with hyperviscosity, hyperbilirubinaemia and respiratory distress.

  8. Oxidative shift in tissue redox potential increases beat-to-beat variability of action potential duration.

    Science.gov (United States)

    Kistamás, Kornél; Hegyi, Bence; Váczi, Krisztina; Horváth, Balázs; Bányász, Tamás; Magyar, János; Szentandrássy, Norbert; Nánási, Péter P

    2015-07-01

    Profound changes in tissue redox potential occur in the heart under conditions of oxidative stress frequently associated with cardiac arrhythmias. Since beat-to-beat variability (short term variability, SV) of action potential duration (APD) is a good indicator of arrhythmia incidence, the aim of this work was to study the influence of redox changes on SV in isolated canine ventricular cardiomyocytes using a conventional microelectrode technique. The redox potential was shifted toward a reduced state using a reductive cocktail (containing dithiothreitol, glutathione, and ascorbic acid) while oxidative changes were initiated by superfusion with H2O2. Redox effects were evaluated as changes in "relative SV" determined by comparing SV changes with the concomitant APD changes. Exposure of myocytes to the reductive cocktail decreased SV significantly without any detectable effect on APD. Application of H2O2 increased both SV and APD, but the enhancement of SV was the greater, so relative SV increased. Longer exposure to H2O2 resulted in the development of early afterdepolarizations accompanied by tremendously increased SV. Pretreatment with the reductive cocktail prevented both elevation in relative SV and the development of afterdepolarizations. The results suggest that the increased beat-to-beat variability during an oxidative stress contributes to the generation of cardiac arrhythmias.

  9. 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

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

    Science.gov (United States)

    Muñoz, Fabián; Fuentealba, Pablo

    2012-01-01

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

  11. Acute alterations of somatodendritic action potential dynamics in hippocampal CA1 pyramidal cells after kainate-induced status epilepticus in mice.

    Directory of Open Access Journals (Sweden)

    Daniel Minge

    Full Text Available Pathophysiological remodeling processes at an early stage of an acquired epilepsy are critical but not well understood. Therefore, we examined acute changes in action potential (AP dynamics immediately following status epilepticus (SE in mice. SE was induced by intraperitoneal (i.p. injection of kainate, and behavioral manifestation of SE was monitored for 3-4 h. After this time interval CA1 pyramidal cells were studied ex vivo with whole-cell current-clamp and Ca(2+ imaging techniques in a hippocampal slice preparation. Following acute SE both resting potential and firing threshold were modestly depolarized (2-5 mV. No changes were seen in input resistance or membrane time constant, but AP latency was prolonged and AP upstroke velocity reduced following acute SE. All cells showed an increase in AP halfwidth and regular (rather than burst firing, and in a fraction of cells the notch, typically preceding spike afterdepolarization (ADP, was absent following acute SE. Notably, the typical attenuation of backpropagating action potential (b-AP-induced Ca(2+ signals along the apical dendrite was strengthened following acute SE. The effects of acute SE on the retrograde spread of excitation were mimicked by applying the Kv4 current potentiating drug NS5806. Our data unveil a reduced somatodendritic excitability in hippocampal CA1 pyramidal cells immediately after acute SE with a possible involvement of both Na(+ and K(+ current components.

  12. 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.

  13. Loading dynamics of a sliding DNA clamp.

    KAUST Repository

    Cho, Won-Ki; Jergic, Slobodan; Kim, Daehyung; Dixon, Nicholas E; Lee, Jong-Bong

    2014-01-01

    8° during clamp closure. The single-molecule polarization and FRET studies thus revealed the real-time dynamics of the ATP-hydrolysis-dependent 3D conformational change of the β clamp during loading at a ss/dsDNA junction.

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

    NARCIS (Netherlands)

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

    2009-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

  17. Imaging Action Potential in Single Mammalian Neurons by Tracking the Accompanying Sub-Nanometer Mechanical Motion.

    Science.gov (United States)

    Yang, Yunze; Liu, Xian-Wei; Wang, Hui; Yu, Hui; Guan, Yan; Wang, Shaopeng; Tao, Nongjian

    2018-03-28

    Action potentials in neurons have been studied traditionally by intracellular electrophysiological recordings and more recently by the fluorescence detection methods. Here we describe a label-free optical imaging method that can measure mechanical motion in single cells with a sub-nanometer detection limit. Using the method, we have observed sub-nanometer mechanical motion accompanying the action potential in single mammalian neurons by averaging the repeated action potential spikes. The shape and width of the transient displacement are similar to those of the electrically recorded action potential, but the amplitude varies from neuron to neuron, and from one region of a neuron to another, ranging from 0.2-0.4 nm. The work indicates that action potentials may be studied noninvasively in single mammalian neurons by label-free imaging of the accompanying sub-nanometer mechanical motion.

  18. Meju, unsalted soybeans fermented with Bacillus subtilis and Aspergilus oryzae, potentiates insulinotropic actions and improves hepatic insulin sensitivity in diabetic rats.

    Science.gov (United States)

    Yang, Hye Jeong; Kwon, Dae Young; Kim, Min Jung; Kang, Suna; Park, Sunmin

    2012-05-02

    Although soybeans have the ability to attenuate insulin resistance, it is insufficient to alleviate type 2 diabetic symptoms and different types of fermented soybeans may have even better anti-diabetic effects. Meju, unsalted fermented soybeans exhibited better insulin sensitizing and insulinotropic actions than unfermented cooked soybeans (CSB). We investigated whether meju fermented in the traditional (TMS) manner for 60 days and meju fermented in the standardized (MMS) method inoculating Bacillus subtilis and Aspergillus oryzae for 6 days modulated insulin resistance, insulin secretion, and pancreatic β-cell growth and survival in 90% pancreatectomized (Px) diabetic rats, a moderate and non-obese type 2 diabetic animal model. Diabetic rats were divided into 3 groups: 1) TMS (n = 20), 2) MMS (n = 20) or 3) casein (control; n = 20). Rats were provided with a high fat diet (40 energy % fat) containing assigned 10% meju for 8 weeks. At the end of experiment insulin resistance and insulin secretion capacity were measured by euglycemic hyperinsulinemic clamp and by hyperglycemic clamp, respectively. Additionally, β-cell mass and islet morphohometry were determined by immunohistochemistry and insulin signaling in the liver was measured by western blot. TMS and MMS increased isoflavonoid aglycones much more than CSB. CSB and TMS/MMS improved glucose tolerance in diabetic rats but the mechanism was different between treatments (P MMS enhanced only hepatic insulin sensitivity through activating insulin signaling in diabetic rats (P MMS, but not CSB, potentiated glucose-stimulated insulin secretion and β-cell mass (P MMS had better insulinotropic actions than the control (P MMS, especially when fermented with Bacillus subtilis and Aspergillus oryzae, was superior to CSB by increasing isoflavonoid aglycones and small peptides with regard to type 2 diabetic rats.

  19. [Loudness optimized registration of compound action potential in cochlear implant recipients].

    Science.gov (United States)

    Berger, Klaus; Hocke, Thomas; Hessel, Horst

    2017-11-01

    Background Postoperative measurements of compound action potentials are not always possible due to the insufficient acceptance of the CI-recipients. This study investigated the impact of different parameters on the acceptance of the measurements. Methods Compound action potentials of 16 CI recipients were measured with different pulse-widths. Recipients performed a loudness rating at the potential thresholds with the different sequences. Results Compound action potentials obtained with higher pulse-widths were rated softer than those obtained with smaller pulse-widths. Conclusions Compound action potentials measured with higher pulse-widths generate a gap between loudest acceptable presentation level and potential threshold. This gap contributes to a higher acceptance of postoperative measurements. Georg Thieme Verlag KG Stuttgart · New York.

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

    Science.gov (United States)

    Crago, Patrick E; Makowski, Nathaniel S

    2014-10-01

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

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

    Science.gov (United States)

    Lu, Siyuan; Madhukar, Anupam

    2013-02-01

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

  2. The cardiovascular effects of aortic clamping and unclamping

    African Journals Online (AJOL)

    aortic clamping is that afterload and blood pressure increase, and ... individually, albeit they interact with each other. The degree of ... position of the aortic clamp, the greater the increase ... the increase in preload in response to aortic clamping.

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

    International Nuclear Information System (INIS)

    Kandori, Akihiko; Shimizu, Wataru; Yokokawa, Miki; Kamakura, Shiro; Miyatake, Kunio; Murakami, Masahiro; Miyashita, Tsuyoshi; Ogata, Kuniomi; Tsukada, Keiji

    2004-01-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    The role of conscious intention in relation to motoric movements has become a major topic of investigation in neuroscience. Traditionally, reports of conscious intention have been compared to various features of the readiness-potential (RP) – an electrophysiological signal that appears before...... electrophysiological “intention potential” above the mid-frontal areas at the time participants formed a distal intention. This potential was only found when the distal intention was self-paced and not when the intention was formed in response to an external cue....

  5. Crystal structure of DNA polymerase III β sliding clamp from Mycobacterium tuberculosis.

    Science.gov (United States)

    Gui, Wen-Jun; Lin, Shi-Qiang; Chen, Yuan-Yuan; Zhang, Xian-En; Bi, Li-Jun; Jiang, Tao

    2011-02-11

    The sliding clamp is a key component of DNA polymerase III (Pol III) required for genome replication. It is known to function with diverse DNA repair proteins and cell cycle-control proteins, making it a potential drug target. To extend our understanding of the structure/function relationship of the sliding clamp, we solved the crystal structure of the sliding clamp from Mycobacterium tuberculosis (M. tuberculosis), a human pathogen that causes most cases of tuberculosis (TB). The sliding clamp from M. tuberculosis forms a ring-shaped head-to-tail dimer with three domains per subunit. Each domain contains two α helices in the inner ring that lie against two β sheets in the outer ring. Previous studies have indicated that many Escherichia coli clamp-binding proteins have a conserved LF sequence, which is critical for binding to the hydrophobic region of the sliding clamp. Here, we analyzed the binding affinities of the M. tuberculosis sliding clamp and peptides derived from the α and δ subunits of Pol III, which indicated that the LF motif also plays an important role in the binding of the α and δ subunits to the sliding clamp of M. tuberculosis. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Application of active electrode compensation to perform continuous voltage-clamp recordings with sharp microelectrodes.

    Science.gov (United States)

    Gómez-González, J F; Destexhe, A; Bal, T

    2014-10-01

    Electrophysiological recordings of single neurons in brain tissues are very common in neuroscience. Glass microelectrodes filled with an electrolyte are used to impale the cell membrane in order to record the membrane potential or to inject current. Their high resistance induces a high voltage drop when passing current and it is essential to correct the voltage measurements. In particular, for voltage clamping, the traditional alternatives are two-electrode voltage-clamp technique or discontinuous single electrode voltage-clamp (dSEVC). Nevertheless, it is generally difficult to impale two electrodes in a same neuron and the switching frequency is limited to low frequencies in the case of dSEVC. We present a novel fully computer-implemented alternative to perform continuous voltage-clamp recordings with a single sharp-electrode. To reach such voltage-clamp recordings, we combine an active electrode compensation algorithm (AEC) with a digital controller (AECVC). We applied two types of control-systems: a linear controller (proportional plus integrative controller) and a model-based controller (optimal control). We compared the performance of the two methods to dSEVC using a dynamic model cell and experiments in brain slices. The AECVC method provides an entirely digital method to perform continuous recording and smooth switching between voltage-clamp, current clamp or dynamic-clamp configurations without introducing artifacts.

  7. A Parsimonious Model of the Rabbit Action Potential Elucidates the Minimal Physiological Requirements for Alternans and Spiral Wave Breakup.

    Science.gov (United States)

    Gray, Richard A; Pathmanathan, Pras

    2016-10-01

    Elucidating the underlying mechanisms of fatal cardiac arrhythmias requires a tight integration of electrophysiological experiments, models, and theory. Existing models of transmembrane action potential (AP) are complex (resulting in over parameterization) and varied (leading to dissimilar predictions). Thus, simpler models are needed to elucidate the "minimal physiological requirements" to reproduce significant observable phenomena using as few parameters as possible. Moreover, models have been derived from experimental studies from a variety of species under a range of environmental conditions (for example, all existing rabbit AP models incorporate a formulation of the rapid sodium current, INa, based on 30 year old data from chick embryo cell aggregates). Here we develop a simple "parsimonious" rabbit AP model that is mathematically identifiable (i.e., not over parameterized) by combining a novel Hodgkin-Huxley formulation of INa with a phenomenological model of repolarization similar to the voltage dependent, time-independent rectifying outward potassium current (IK). The model was calibrated using the following experimental data sets measured from the same species (rabbit) under physiological conditions: dynamic current-voltage (I-V) relationships during the AP upstroke; rapid recovery of AP excitability during the relative refractory period; and steady-state INa inactivation via voltage clamp. Simulations reproduced several important "emergent" phenomena including cellular alternans at rates > 250 bpm as observed in rabbit myocytes, reentrant spiral waves as observed on the surface of the rabbit heart, and spiral wave breakup. Model variants were studied which elucidated the minimal requirements for alternans and spiral wave break up, namely the kinetics of INa inactivation and the non-linear rectification of IK.The simplicity of the model, and the fact that its parameters have physiological meaning, make it ideal for engendering generalizable mechanistic

  8. Action potentials in retinal ganglion cells are initiated at the site of maximal curvature of the extracellular potential.

    Science.gov (United States)

    Eickenscheidt, Max; Zeck, Günther

    2014-06-01

    The initiation of an action potential by extracellular stimulation occurs after local depolarization of the neuronal membrane above threshold. Although the technique shows remarkable clinical success, the site of action and the relevant stimulation parameters are not completely understood. Here we identify the site of action potential initiation in rabbit retinal ganglion cells (RGCs) interfaced to an array of extracellular capacitive stimulation electrodes. We determine which feature of the extracellular potential governs action potential initiation by simultaneous stimulation and recording RGCs interfaced in epiretinal configuration. Stimulation electrodes were combined to areas of different size and were presented at different positions with respect to the RGC. Based on stimulation by electrodes beneath the RGC soma and simultaneous sub-millisecond latency measurement we infer axonal initiation at the site of maximal curvature of the extracellular potential. Stimulation by electrodes at different positions along the axon reveals a nearly constant threshold current density except for a narrow region close to the cell soma. These findings are explained by the concept of the activating function modified to consider a region of lower excitability close to the cell soma. We present a framework how to estimate the site of action potential initiation and the stimulus required to cross threshold in neurons tightly interfaced to capacitive stimulation electrodes. Our results underscore the necessity of rigorous electrical characterization of the stimulation electrodes and of the interfaced neural tissue.

  9. Deleting the accessory subunit KChIP2 results in loss of I(to,f) and increased I(K,slow) that maintains normal action potential configuration

    DEFF Research Database (Denmark)

    Thomsen, Morten B; Sosunov, Eugene A; Anyukhovsky, Evgeny P

    2008-01-01

    BACKGROUND: Four voltage-gated potassium currents, I(to,f) (K(V)4.2), I(to,s) (K(V)1.4), I(K,slow) (K(V)1.5+K(V)2.1), and I(SS) (TASK1), govern murine ventricular repolarization. Although the accessory subunit KChIP2 influences I(to,f) expression, in preliminary experiments we found that action...... potential duration (APD) is maintained in KChIP2 knockout mice. OBJECTIVE: We tested the role of KChIP2 in regulating APD and studied the underlying ionic currents. METHODS: We used microelectrode techniques, whole-cell patch clamp studies, and real-time polymerase chain reaction amplification...... to characterize ventricular repolarization and its determinants in wild-type and KChIP2(-/-) mice. RESULTS: Despite comparable baseline action potentials, APD was more markedly prolonged by 4-aminopyridine (4-AP) in KChIP2(-/-) preparations. Peak K(+) current densities were similar in wild-type and KChIP2...

  10. 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. PMID:24465197

  11. Mechanics of wafer bonding: Effect of clamping

    Science.gov (United States)

    Turner, K. T.; Thouless, M. D.; Spearing, S. M.

    2004-01-01

    A mechanics-based model is developed to examine the effects of clamping during wafer bonding processes. The model provides closed-form expressions that relate the initial geometry and elastic properties of the wafers to the final shape of the bonded pair and the strain energy release rate at the interface for two different clamping configurations. The results demonstrate that the curvature of bonded pairs may be controlled through the use of specific clamping arrangements during the bonding process. Furthermore, it is demonstrated that the strain energy release rate depends on the clamping configuration and that using applied loads usually leads to an undesirable increase in the strain energy release rate. The results are discussed in detail and implications for process development and bonding tool design are highlighted.

  12. Formal Design Review Foot Clamp Modification

    International Nuclear Information System (INIS)

    OTEN, T.C.

    2000-01-01

    This report documents the Design Review performed for the foot clamp modification. The report documents the acceptability of the design, identifies the documents that were reviewed, the scope of the review and the members of the review team

  13. Core clamping device for a nuclear reactor

    International Nuclear Information System (INIS)

    Guenther, R.W.

    1974-01-01

    The core clamping device for a fast neutron reactor includes clamps to support the fuel zone against the pressure vessel. The clamps are arranged around the circumference of the core. They consist of torsion bars arranged parallel at some distance around the core with lever arms attached to the ends whose force is directed in the opposite direction, pressing against the wall of the pressure vessel. The lever arms and pressure plates also actuated by the ends of the torsion bars transfer the stress, the pressure plates acting upon the fuel elements or fuel assemblies. Coupling between the ends of the torsion bars and the pressure plates is achieved by end carrier plates directly attached to the torsion bars and radially movable. This clamping device follows the thermal expansions of the core, allows specific elements to be disengaged in sections and saves space between the core and the neutron reflectors. (DG) [de

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    NARCIS (Netherlands)

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

    2007-01-01

    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

  17. Changes in the action potential and transient outward potassium current in cardiomyocytes during acute cardiac rejection in rats.

    Science.gov (United States)

    Luo, Wenqi; Jia, Yixin; Zheng, Shuai; Li, Yan; Han, Jie; Meng, Xu

    2017-01-01

    Acute cardiac rejection contributes to the changes in the electrophysiological properties of grafted hearts. However, the electrophysiological changes of cardiomyocytes during acute cardiac rejection are still unknown. An understanding of the electrophysiological mechanisms of cardiomyocytes could improve the diagnosis and treatment of acute cardiac rejection. So it is important to characterize the changes in the action potential ( AP ) and the transient outward potassium current ( I to ) in cardiomyocytes during acute cardiac rejection. Heterotopic heart transplantation was performed in allogeneic [Brown Norway (BN)-to-Lewis] and isogeneic (BN-to-BN) rats. Twenty models were established in each group. Ten recipients were sacrificed at the 2nd day and the other ten recipients were sacrificed at the 4 th day after the operation in each group. Histopathological examinations of the grafted hearts were performed in half of the recipients in each group randomly. The other half of the grafted hearts were excised rapidly and enzymatically dissociated to obtain single cardiomyocytes. The AP and I to current were recorded using the whole cell patch-clamp technique. Forty grafted hearts were successfully harvested and used in experiments. Histologic examination showed mild rejection at the 2 nd day and moderate rejection at the 4 th day in the allogeneic group after cardiac transplantation, while no evidence of histologic lesions of rejection were observed in the isogeneic group. Compared with the isogeneic group, the action potential duration ( APD ) of cardiomyocytes in the allogeneic group was significantly prolonged ( APD 90 was 49.28±5.621 mV in the isogeneic group and 88.08±6.445 mV in the allogeneic group at the 2 nd day, P=0.0016; APD 90 was 59.34±5.183 mV in the isogeneic group and 104.0±9.523 mV in the allogeneic group at the 4 th day, P=0.0064). The current density of I to was significantly decreased at the 4 th day after cardiac transplantation. The APD of

  18. 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

    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......-to-moderate olfactory nerve input, an action potential was initiated near the soma and then back-propagated into the primary dendrite. As olfactory nerve input increased, the initiation site suddenly shifted to the distal primary dendrite. Multi-compartmental modeling indicated that this abrupt shift of the spike......-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...

  19. 7 CFR 1945.19 - Reporting potential natural disasters and initial actions.

    Science.gov (United States)

    2010-01-01

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

  20. Selective Arterial Clamping Versus Hilar Clamping for Minimally Invasive Partial Nephrectomy.

    Science.gov (United States)

    Yezdani, Mona; Yu, Sue-Jean; Lee, David I

    2016-05-01

    Partial nephrectomy has become an accepted treatment of cT1 renal masses as it provides improved long-term renal function compared to radical nephrectomy (Campbell et al. J Urol. 182:1271-9, 2009). Hilar clamping is utilized to help reduce bleeding and improve visibility during tumor resection. However, concern over risk of kidney injury with hilar clamping has led to new techniques to reduce length of warm ischemia time (WIT) during partial nephrectomy. These techniques have progressed over the years starting with early hilar unclamping, controlled hypotension during tumor resection, selective arterial clamping, minimal margin techniques, and off-clamp procedures. Selective arterial clamping has progressed significantly over the years. The main question is what are the exact short- and long-term renal effects from increasing clamp time. Moreover, does it make sense to perform these more time-consuming or more complex procedures if there is no long-term preservation of kidney function? More recent studies have shown no difference in renal function 6 months from surgery when selective arterial clamping or even hilar clamping is employed, although there is short-term improved decline in estimated glomerular filtration rate (eGFR) with selective clamping and off-clamp techniques (Komninos et al. BJU Int. 115:921-8, 2015; Shah et al. 117:293-9, 2015; Kallingal et al. BJU Int. doi: 10.1111/bju.13192, 2015). This paper reviews the progression of total hilar clamping to selective arterial clamping (SAC) and the possible difference its use makes on long-term renal function. SAC may be attempted based on surgeon's decision-making, but may be best used for more complex, larger, more central or hilar tumors and in patients who have renal insufficiency at baseline or a solitary kidney.

  1. Recovery of Action Potentials and Twitches after K-contractures in Frog Skeletal Muscle(Physiology)

    OpenAIRE

    Atsuko, Suzuki; Ibuki, Shirakawa; Kazunari, Noguchi; Hirohiko, Kishi; Haruo, Sugi; Department of Physiology, School of Medicine, Teikyo University:(Present office)Department of Physical Therapy, Health Science University; Department of Physiology, School of Medicine, Teikyo University; Department of Physiology, School of Medicine, Teikyo University; Department of Physiology, School of Medicine, Teikyo University; Department of Physiology, School of Medicine, Teikyo University

    2004-01-01

    To give information about intracellular Ca^ translocation during and after K-contractures in vertebrate skeletal muscle fibers, we examined recovery of action potentials and twitches after interruption and spontaneous relaxation of K-contractures at low temperature (3℃) that greatly reduced the rate of Ca^ reuptake by the sarcoplasmic reticulum. On membrane repolarization interrupting K-contractures, the amplitude of both action potentials and twitches recovered quickly, while the falling pha...

  2. Hypertrophic cardiomyopathy-linked mutation in troponin T causes myofibrillar disarray and pro-arrhythmic action potential changes in human iPSC cardiomyocytes.

    Science.gov (United States)

    Wang, Lili; Kim, Kyungsoo; Parikh, Shan; Cadar, Adrian Gabriel; Bersell, Kevin R; He, Huan; Pinto, Jose R; Kryshtal, Dmytro O; Knollmann, Bjorn C

    2018-01-01

    Mutations in cardiac troponin T (TnT) are linked to increased risk of ventricular arrhythmia and sudden death despite causing little to no cardiac hypertrophy. Studies in mice suggest that the hypertrophic cardiomyopathy (HCM)-associated TnT-I79N mutation increases myofilament Ca sensitivity and is arrhythmogenic, but whether findings from mice translate to human cardiomyocyte electrophysiology is not known. To study the effects of the TnT-I79N mutation in human cardiomyocytes. Using CRISPR/Cas9, the TnT-I79N mutation was introduced into human induced pluripotent stem cells (hiPSCs). We then used the matrigel mattress method to generate single rod-shaped cardiomyocytes (CMs) and studied contractility, Ca handling and electrophysiology. Compared to isogenic control hiPSC-CMs, TnT-I79N hiPSC-CMs exhibited sarcomere disorganization, increased systolic function and impaired relaxation. The Ca-dependence of contractility was leftward shifted in mutation containing cardiomyocytes, demonstrating increased myofilament Ca sensitivity. In voltage-clamped hiPSC-CMs, TnT-I79N reduced intracellular Ca transients by enhancing cytosolic Ca buffering. These changes in Ca handling resulted in beat-to-beat instability and triangulation of the cardiac action potential, which are predictors of arrhythmia risk. The myofilament Ca sensitizer EMD57033 produced similar action potential triangulation in control hiPSC-CMs. The TnT-I79N hiPSC-CM model not only reproduces key cellular features of TnT-linked HCM such as myofilament disarray, hypercontractility and diastolic dysfunction, but also suggests that this TnT mutation causes pro-arrhythmic changes of the human ventricular action potential. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. 21 CFR 882.4460 - Neurosurgical head holder (skull clamp).

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Neurosurgical head holder (skull clamp). 882.4460... holder (skull clamp). (a) Identification. A neurosurgical head holder (skull clamp) is a device used to clamp the patient's skull to hold head and neck in a particular position during surgical procedures. (b...

  4. Variable Action Potential Backpropagation during Tonic Firing and Low-Threshold Spike Bursts in Thalamocortical But Not Thalamic Reticular Nucleus Neurons.

    Science.gov (United States)

    Connelly, William M; Crunelli, Vincenzo; Errington, Adam C

    2017-05-24

    Backpropagating action potentials (bAPs) are indispensable in dendritic signaling. Conflicting Ca 2+ -imaging data and an absence of dendritic recording data means that the extent of backpropagation in thalamocortical (TC) and thalamic reticular nucleus (TRN) neurons remains unknown. Because TRN neurons signal electrically through dendrodendritic gap junctions and possibly via chemical dendritic GABAergic synapses, as well as classical axonal GABA release, this lack of knowledge is problematic. To address this issue, we made two-photon targeted patch-clamp recordings from rat TC and TRN neuron dendrites to measure bAPs directly. These recordings reveal that "tonic"' and low-threshold-spike (LTS) "burst" APs in both cell types are always recorded first at the soma before backpropagating into the dendrites while undergoing substantial distance-dependent dendritic amplitude attenuation. In TC neurons, bAP attenuation strength varies according to firing mode. During LTS bursts, somatic AP half-width increases progressively with increasing spike number, allowing late-burst spikes to propagate more efficiently into the dendritic tree compared with spikes occurring at burst onset. Tonic spikes have similar somatic half-widths to late burst spikes and undergo similar dendritic attenuation. In contrast, in TRN neurons, AP properties are unchanged between LTS bursts and tonic firing and, as a result, distance-dependent dendritic attenuation remains consistent across different firing modes. Therefore, unlike LTS-associated global electrical and calcium signals, the spatial influence of bAP signaling in TC and TRN neurons is more restricted, with potentially important behavioral-state-dependent consequences for synaptic integration and plasticity in thalamic neurons. SIGNIFICANCE STATEMENT In most neurons, action potentials (APs) initiate in the axosomatic region and propagate into the dendritic tree to provide a retrograde signal that conveys information about the level of

  5. Sensitivity to structure in action sequences: An infant event-related potential study.

    Science.gov (United States)

    Monroy, Claire D; Gerson, Sarah A; Domínguez-Martínez, Estefanía; Kaduk, Katharina; Hunnius, Sabine; Reid, Vincent

    2017-05-06

    Infants are sensitive to structure and patterns within continuous streams of sensory input. This sensitivity relies on statistical learning, the ability to detect predictable regularities in spatial and temporal sequences. Recent evidence has shown that infants can detect statistical regularities in action sequences they observe, but little is known about the neural process that give rise to this ability. In the current experiment, we combined electroencephalography (EEG) with eye-tracking to identify electrophysiological markers that indicate whether 8-11-month-old infants detect violations to learned regularities in action sequences, and to relate these markers to behavioral measures of anticipation during learning. In a learning phase, infants observed an actor performing a sequence featuring two deterministic pairs embedded within an otherwise random sequence. Thus, the first action of each pair was predictive of what would occur next. One of the pairs caused an action-effect, whereas the second did not. In a subsequent test phase, infants observed another sequence that included deviant pairs, violating the previously observed action pairs. Event-related potential (ERP) responses were analyzed and compared between the deviant and the original action pairs. Findings reveal that infants demonstrated a greater Negative central (Nc) ERP response to the deviant actions for the pair that caused the action-effect, which was consistent with their visual anticipations during the learning phase. Findings are discussed in terms of the neural and behavioral processes underlying perception and learning of structured action sequences. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Cell-type-dependent action potentials and voltage-gated currents in mouse fungiform taste buds.

    Science.gov (United States)

    Kimura, Kenji; Ohtubo, Yoshitaka; Tateno, Katsumi; Takeuchi, Keita; Kumazawa, Takashi; Yoshii, Kiyonori

    2014-01-01

    Taste receptor cells fire action potentials in response to taste substances to trigger non-exocytotic neurotransmitter release in type II cells and exocytotic release in type III cells. We investigated possible differences between these action potentials fired by mouse taste receptor cells using in situ whole-cell recordings, and subsequently we identified their cell types immunologically with cell-type markers, an IP3 receptor (IP3 R3) for type II cells and a SNARE protein (SNAP-25) for type III cells. Cells not immunoreactive to these antibodies were examined as non-IRCs. Here, we show that type II cells and type III cells fire action potentials using different ionic mechanisms, and that non-IRCs also fire action potentials with either of the ionic mechanisms. The width of action potentials was significantly narrower and their afterhyperpolarization was deeper in type III cells than in type II cells. Na(+) current density was similar in type II cells and type III cells, but it was significantly smaller in non-IRCs than in the others. Although outwardly rectifying current density was similar between type II cells and type III cells, tetraethylammonium (TEA) preferentially suppressed the density in type III cells and the majority of non-IRCs. Our mathematical model revealed that the shape of action potentials depended on the ratio of TEA-sensitive current density and TEA-insensitive current one. The action potentials of type II cells and type III cells under physiological conditions are discussed. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

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

    Science.gov (United States)

    Casale, Amanda E.; McCormick, David A.

    2012-01-01

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

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

    Science.gov (United States)

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

    2017-06-01

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

  9. Piezoresistive cantilever force-clamp system

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sung-Jin; Petzold, Bryan C.; Pruitt, Beth L. [Department of Mechanical Engineering, Stanford University, Stanford, California 94305 (United States); Goodman, Miriam B. [Department of Molecular and Cellular Physiology, Stanford University, Stanford, California 94305 (United States)

    2011-04-15

    We present a microelectromechanical device-based tool, namely, a force-clamp system that sets or ''clamps'' the scaled force and can apply designed loading profiles (e.g., constant, sinusoidal) of a desired magnitude. The system implements a piezoresistive cantilever as a force sensor and the built-in capacitive sensor of a piezoelectric actuator as a displacement sensor, such that sample indentation depth can be directly calculated from the force and displacement signals. A programmable real-time controller operating at 100 kHz feedback calculates the driving voltage of the actuator. The system has two distinct modes: a force-clamp mode that controls the force applied to a sample and a displacement-clamp mode that controls the moving distance of the actuator. We demonstrate that the system has a large dynamic range (sub-nN up to tens of {mu}N force and nm up to tens of {mu}m displacement) in both air and water, and excellent dynamic response (fast response time, <2 ms and large bandwidth, 1 Hz up to 1 kHz). In addition, the system has been specifically designed to be integrated with other instruments such as a microscope with patch-clamp electronics. We demonstrate the capabilities of the system by using it to calibrate the stiffness and sensitivity of an electrostatic actuator and to measure the mechanics of a living, freely moving Caenorhabditis elegans nematode.

  10. Position-dependent patterning of spontaneous action potentials in immature cochlear inner hair cells

    Science.gov (United States)

    Johnson, Stuart L.; Eckrich, Tobias; Kuhn, Stephanie; Zampini, Valeria; Franz, Christoph; Ranatunga, Kishani M.; Roberts, Terri P.; Masetto, Sergio; Knipper, Marlies; Kros, Corné J.; Marcotti, Walter

    2011-01-01

    Spontaneous action potential activity is crucial for mammalian sensory system development. In the auditory system, patterned firing activity has been observed in immature spiral ganglion cells and brain-stem neurons and is likely to depend on cochlear inner hair cell (IHC) action potentials. It remains uncertain whether spiking activity is intrinsic to developing IHCs and whether it shows patterning. We found that action potentials are intrinsically generated by immature IHCs of altricial rodents and that apical IHCs exhibit bursting activity as opposed to more sustained firing in basal cells. We show that the efferent neurotransmitter ACh, by fine-tuning the IHC’s resting membrane potential (Vm), is crucial for the bursting pattern in apical cells. Endogenous extracellular ATP also contributes to the Vm of apical and basal IHCs by activating SK2 channels. We hypothesize that the difference in firing pattern along the cochlea instructs the tonotopic differentiation of IHCs and auditory pathway. PMID:21572434

  11. 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.

  12. Differential Regulation of Action Potential Shape and Burst-Frequency Firing by BK and Kv2 Channels in Substantia Nigra Dopaminergic Neurons.

    Science.gov (United States)

    Kimm, Tilia; Khaliq, Zayd M; Bean, Bruce P

    2015-12-16

    Little is known about the voltage-dependent potassium currents underlying spike repolarization in midbrain dopaminergic neurons. Studying mouse substantia nigra pars compacta dopaminergic neurons both in brain slice and after acute dissociation, we found that BK calcium-activated potassium channels and Kv2 channels both make major contributions to the depolarization-activated potassium current. Inhibiting Kv2 or BK channels had very different effects on spike shape and evoked firing. Inhibiting Kv2 channels increased spike width and decreased the afterhyperpolarization, as expected for loss of an action potential-activated potassium conductance. BK inhibition also increased spike width but paradoxically increased the afterhyperpolarization. Kv2 channel inhibition steeply increased the slope of the frequency-current (f-I) relationship, whereas BK channel inhibition had little effect on the f-I slope or decreased it, sometimes resulting in slowed firing. Action potential clamp experiments showed that both BK and Kv2 current flow during spike repolarization but with very different kinetics, with Kv2 current activating later and deactivating more slowly. Further experiments revealed that inhibiting either BK or Kv2 alone leads to recruitment of additional current through the other channel type during the action potential as a consequence of changes in spike shape. Enhancement of slowly deactivating Kv2 current can account for the increased afterhyperpolarization produced by BK inhibition and likely underlies the very different effects on the f-I relationship. The cross-regulation of BK and Kv2 activation illustrates that the functional role of a channel cannot be defined in isolation but depends critically on the context of the other conductances in the cell. This work shows that BK calcium-activated potassium channels and Kv2 voltage-activated potassium channels both regulate action potentials in dopamine neurons of the substantia nigra pars compacta. Although both

  13. Action Potential Dynamics in Fine Axons Probed with an Axonally Targeted Optical Voltage Sensor.

    Science.gov (United States)

    Ma, Yihe; Bayguinov, Peter O; Jackson, Meyer B

    2017-01-01

    The complex and malleable conduction properties of axons determine how action potentials propagate through extensive axonal arbors to reach synaptic terminals. The excitability of axonal membranes plays a major role in neural circuit function, but because most axons are too thin for conventional electrical recording, their properties remain largely unexplored. To overcome this obstacle, we used a genetically encoded hybrid voltage sensor (hVOS) harboring an axonal targeting motif. Expressing this probe in transgenic mice enabled us to monitor voltage changes optically in two populations of axons in hippocampal slices, the large axons of dentate granule cells (mossy fibers) in the stratum lucidum of the CA3 region and the much finer axons of hilar mossy cells in the inner molecular layer of the dentate gyrus. Action potentials propagated with distinct velocities in each type of axon. Repetitive firing broadened action potentials in both populations, but at an intermediate frequency the degree of broadening differed. Repetitive firing also attenuated action potential amplitudes in both mossy cell and granule cell axons. These results indicate that the features of use-dependent action potential broadening, and possible failure, observed previously in large nerve terminals also appear in much finer unmyelinated axons. Subtle differences in the frequency dependences could influence the propagation of activity through different pathways to excite different populations of neurons. The axonally targeted hVOS probe used here opens up the diverse repertoire of neuronal processes to detailed biophysical study.

  14. IMPORTANT: Fluke is recalling Digital Clamp Meters

    CERN Multimedia

    2013-01-01

    Fluke is voluntarily recalling four models of Digital Clamp Meters: Fluke 373, 374, 375 and 376. If you own one of these clamp meters, please stop using it and send it back to Fluke for repair even if you have not experienced problems.   Description of the problem: "The printed circuit assembly may not be properly fastened to the test lead input jack. This may result in inaccurate voltage readings, including a low or no-voltage reading on a circuit energised with a hazardous voltage, presenting a shock, electrocution or thermal burn hazard." To determine if your clamp meter is affected by this recall notice, and for more information, click here.

  15. Fokker-action principle for a system of particles interacting through a linear potential

    International Nuclear Information System (INIS)

    Rivacoba, A.

    1984-01-01

    A Fokker-action principle for a system of scalar particles interacting through their time-symmetric relativistic generalization of linear potential is obtained. From this action, motion equations and conservation laws for the total energy and angular momentum of the system, in which field contributions are included, are derived. These equations are exactly applied to the problem suggested by Schild of two particles moving in circular concentric orbits

  16. Low-intensity repetitive magnetic stimulation lowers action potential threshold and increases spike firing in layer 5 pyramidal neurons in vitro.

    Science.gov (United States)

    Tang, Alexander D; Hong, Ivan; Boddington, Laura J; Garrett, Andrew R; Etherington, Sarah; Reynolds, John N J; Rodger, Jennifer

    2016-10-29

    Repetitive transcranial magnetic stimulation (rTMS) has become a popular method of modulating neural plasticity in humans. Clinically, rTMS is delivered at high intensities to modulate neuronal excitability. While the high-intensity magnetic field can be targeted to stimulate specific cortical regions, areas adjacent to the targeted area receive stimulation at a lower intensity and may contribute to the overall plasticity induced by rTMS. We have previously shown that low-intensity rTMS induces molecular and structural plasticity in vivo, but the effects on membrane properties and neural excitability have not been investigated. Here we investigated the acute effect of low-intensity repetitive magnetic stimulation (LI-rMS) on neuronal excitability and potential changes on the passive and active electrophysiological properties of layer 5 pyramidal neurons in vitro. Whole-cell current clamp recordings were made at baseline prior to subthreshold LI-rMS (600 pulses of iTBS, n=9 cells from 7 animals) or sham (n=10 cells from 9 animals), immediately after stimulation, as well as 10 and 20min post-stimulation. Our results show that LI-rMS does not alter passive membrane properties (resting membrane potential and input resistance) but hyperpolarises action potential threshold and increases evoked spike-firing frequency. Increases in spike firing frequency were present throughout the 20min post-stimulation whereas action potential (AP) threshold hyperpolarization was present immediately after stimulation and at 20min post-stimulation. These results provide evidence that LI-rMS alters neuronal excitability of excitatory neurons. We suggest that regions outside the targeted region of high-intensity rTMS are susceptible to neuromodulation and may contribute to rTMS-induced plasticity. Copyright © 2016 IBRO. All rights reserved.

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

    Science.gov (United States)

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

    2015-03-10

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

  18. Direct detection of a single evoked action potential with MRS in Lumbricus terrestris.

    Science.gov (United States)

    Poplawsky, Alexander J; Dingledine, Raymond; Hu, Xiaoping P

    2012-01-01

    Functional MRI (fMRI) measures neural activity indirectly by detecting the signal change associated with the hemodynamic response following brain activation. In order to alleviate the temporal and spatial specificity problems associated with fMRI, a number of attempts have been made to detect neural magnetic fields (NMFs) with MRI directly, but have thus far provided conflicting results. In this study, we used MR to detect axonal NMFs in the median giant fiber of the earthworm, Lumbricus terrestris, by examining the free induction decay (FID) with a sampling interval of 0.32 ms. The earthworm nerve cords were isolated from the vasculature and stimulated at the threshold of action potential generation. FIDs were acquired shortly after the stimulation, and simultaneous field potential recordings identified the presence or absence of single evoked action potentials. FIDs acquired when the stimulus did not evoke an action potential were summed as background. The phase of the background-subtracted FID exhibited a systematic change, with a peak phase difference of (-1.2 ± 0.3) × 10(-5) radians occurring at a time corresponding to the timing of the action potential. In addition, we calculated the possible changes in the FID magnitude and phase caused by a simulated action potential using a volume conductor model. The measured phase difference matched the theoretical prediction well in both amplitude and temporal characteristics. This study provides the first evidence for the direct detection of a magnetic field from an evoked action potential using MR. Copyright © 2011 John Wiley & Sons, Ltd.

  19. Tuning permanent magnets with adjustable field clamps

    International Nuclear Information System (INIS)

    Schermer, R.I.

    1987-01-01

    The effective length of a permanent-magnet assembly can be varied by adjusting the geometrical parameters of a field clamp. This paper presents measurements on a representative dipole and quadrupole as the field clamp is withdrawn axially or radially. The detailed behavior depends upon the magnet multipolarity and geometry. As a rule-of-thumb, a 3-mm-thick iron plate placed at one end plane of the magnet will shorten the length by one-third of the magnet bore radius

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

    Science.gov (United States)

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

    2018-01-01

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

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

    Science.gov (United States)

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

    2015-11-01

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

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

    Science.gov (United States)

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

    2016-08-01

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

  3. Selective effects of potassium elevations on glutamate signaling and action potential conduction in hippocampus.

    Science.gov (United States)

    Meeks, Julian P; Mennerick, Steven

    2004-01-07

    High-frequency synaptic transmission is depressed by moderate rises in the extracellular potassium concentration ([K+]o). Previous reports have indicated that depression of action potential signaling may underlie the synaptic depression. Here, we investigated the specific contribution of K+-induced action potential changes to synaptic depression. We found that glutamatergic transmission in the hippocampal area CA1 was significantly depressed by 8-10 mM [K+]o, but that GABAergic transmission remained intact. Riluzole, a drug that slows recovery from inactivation of voltage-gated sodium channels (NaChs), interacts with subthreshold [K+]o to depress afferent volleys and EPSCs strongly. Thus, elevated [K+]o likely depresses synapses by slowing NaCh recovery from inactivation. It is unclear from previous studies whether [K+]o-induced action potential depression is caused by changes in initiation, reliability, or waveform. We investigated these possibilities explicitly. [K+]o-induced afferent volley depression was independent of stimulus strength, suggesting that changes in action potential initiation do not explain [K+]o-induced depression. Measurements of action potentials from single axons revealed that 8 mM [K+]o increased conduction failures in a subpopulation of fibers and depressed action potential amplitude in all fibers. Together, these changes quantitatively account for the afferent volley depression. We estimate that conduction failure explains more than half of the synaptic depression observed at 8 mM [K+]o, with the remaining depression likely explained by waveform changes. These mechanisms of selective sensitivity of glutamate release to [K+]o accumulation represent a unique neuromodulatory mechanism and a brake on runaway excitation.

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

    NARCIS (Netherlands)

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

    1985-01-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  6. 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.

  7. Rosewood oil induces sedation and inhibits compound action potential in rodents.

    Science.gov (United States)

    de Almeida, Reinaldo Nóbrega; Araújo, Demétrius Antonio Machado; Gonçalves, Juan Carlos Ramos; Montenegro, Fabrícia Costa; de Sousa, Damião Pergentino; Leite, José Roberto; Mattei, Rita; Benedito, Marco Antonio Campana; de Carvalho, José Gilberto Barbosa; Cruz, Jader Santos; Maia, José Guilherme Soares

    2009-07-30

    Aniba rosaeodora is an aromatic plant which has been used in Brazil folk medicine due to its sedative effect. Therefore, the purpose of the present study was to evaluate the sedative effect of linalool-rich rosewood oil in mice. In addition we sought to investigate the linalool-rich oil effects on the isolated nerve using the single sucrose-gap technique. Sedative effect was determined by measuring the potentiation of the pentobarbital-induced sleeping time. The compound action potential amplitude was evaluated as a way to detect changes in excitability of the isolated nerve. The results showed that administration of rosewood oil at the doses of 200 and 300 mg/kg significantly decreased latency and increased the duration of sleeping time. On the other hand, the dose of 100 mg/kg potentiated significantly the pentobarbital action decreasing pentobarbital latency time and increasing pentobarbital sleeping time. In addition, the effect of linalool-rich rosewood oil on the isolated nerve of the rat was also investigated through the single sucrose-gap technique. The amplitude of the action potential decreased almost 100% when it was incubated for 30 min at 100 microg/ml. From this study, it is suggested a sedative effect of linalool-rich rosewood oil that could, at least in part, be explained by the reduction in action potential amplitude that provokes a decrease in neuronal excitability.

  8. Clamp and Gas Nozzle for TIG Welding

    Science.gov (United States)

    Gue, G. B.; Goller, H. L.

    1982-01-01

    Tool that combines clamp with gas nozzle is aid to tungsten/inert-gas (TIG) welding in hard-to-reach spots. Tool holds work to be welded while directing a stream of argon gas at weld joint, providing an oxygen-free environment for tungsten-arc welding.

  9. A computational model of the ionic currents, Ca2+ dynamics and action potentials underlying contraction of isolated uterine smooth muscle.

    Directory of Open Access Journals (Sweden)

    Wing-Chiu Tong

    2011-04-01

    Full Text Available Uterine contractions during labor are discretely regulated by rhythmic action potentials (AP of varying duration and form that serve to determine calcium-dependent force production. We have employed a computational biology approach to develop a fuller understanding of the complexity of excitation-contraction (E-C coupling of uterine smooth muscle cells (USMC. Our overall aim is to establish a mathematical platform of sufficient biophysical detail to quantitatively describe known uterine E-C coupling parameters and thereby inform future empirical investigations of physiological and pathophysiological mechanisms governing normal and dysfunctional labors. From published and unpublished data we construct mathematical models for fourteen ionic currents of USMCs: Ca2+ currents (L- and T-type, Na+ current, an hyperpolarization-activated current, three voltage-gated K+ currents, two Ca2+-activated K+ current, Ca2+-activated Cl current, non-specific cation current, Na+-Ca2+ exchanger, Na+-K+ pump and background current. The magnitudes and kinetics of each current system in a spindle shaped single cell with a specified surface area:volume ratio is described by differential equations, in terms of maximal conductances, electrochemical gradient, voltage-dependent activation/inactivation gating variables and temporal changes in intracellular Ca2+ computed from known Ca2+ fluxes. These quantifications are validated by the reconstruction of the individual experimental ionic currents obtained under voltage-clamp. Phasic contraction is modeled in relation to the time constant of changing [Ca2+]i. This integrated model is validated by its reconstruction of the different USMC AP configurations (spikes, plateau and bursts of spikes, the change from bursting to plateau type AP produced by estradiol and of simultaneous experimental recordings of spontaneous AP, [Ca2+]i and phasic force. In summary, our advanced mathematical model provides a powerful tool to

  10. 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.

  11. Action potential conduction between a ventricular cell model and an isolated ventricular cell

    NARCIS (Netherlands)

    Wilders, R.; Kumar, R.; Joyner, R. W.; Jongsma, H. J.; Verheijck, E. E.; Golod, D.; van Ginneken, A. C.; Goolsby, W. N.

    1996-01-01

    We used the Luo and Rudy (LR) mathematical model of the guinea pig ventricular cell coupled to experimentally recorded guinea pig ventricular cells to investigate the effects of geometrical asymmetry on action potential propagation. The overall correspondence of the LR cell model with the recorded

  12. Quantitative analysis of single muscle fibre action potentials recorded at known distances

    NARCIS (Netherlands)

    Albers, B.A.; Put, J.H.M.; Wallinga, W.; Wirtz, P.

    1989-01-01

    In vivo records of single fibre action potentials (SFAPs) have always been obtained at unknown distance from the active muscle fibre. A new experimental method has been developed enabling the derivation of the recording distance in animal experiments. A single fibre is stimulated with an

  13. Changes in time and frequency related aspects of motor unit action potentials during fatigue

    NARCIS (Netherlands)

    Wallinga, W.; Bouwens, Jeroen S.; Baten, Christian T.M.

    1996-01-01

    During fatigue the shape of motor unit action potentials (MUAPs) change. Characteristics of the MUAPs described before concern several time related aspects. No attention has been given to the frequency spectrum changes of MUAPS. The median frequency of MUAPS has now been determined for motor units

  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. 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…

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

    Science.gov (United States)

    Farren, Margaret; Crotty, Yvonne; Kilboy, Laura

    2015-01-01

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

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

    NARCIS (Netherlands)

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

    1988-01-01

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

  18. Anodal sensory nerve action potentials: From physiological understanding to potential clinical applicability.

    Science.gov (United States)

    Leote, Joao; Pereira, Pedro; Cabib, Christopher; Cipullo, Federica; Valls-Sole, Josep

    2016-06-01

    Low-intensity electrical stimuli of digital nerves may generate a double peak potential (DPp), composed of a cathodal (caAP) and an anodal (anAP) potential in orthodromic recordings. We studied the effects on caAP and anAP of stimuli of variable intensity, duration, and frequency. We also applied a conditioning stimulus to study potential differences in recovery time. The anAP was obtained in 33 of 40 healthy subjects (82.5%) and 4 of 20 patients with various types of sensory neuropathies (20%). Changes in stimulus duration and intensity had reciprocal effects on the amplitude of the anAP and the caAP. There were significant differences in recovery time between caAP and anAP after a conditioning stimulus. The caAP and anAP are 2 interdependent waveforms generated by different effects of the same stimulus over axons at the verge of depolarization. Muscle Nerve 53: 897-905, 2016. © 2015 Wiley Periodicals, Inc.

  19. Action potential-based MEA platform for in vitro screening of drug-induced cardiotoxicity using human iPSCs and rat neonatal myocytes.

    Science.gov (United States)

    Jans, Danny; Callewaert, Geert; Krylychkina, Olga; Hoffman, Luis; Gullo, Francesco; Prodanov, Dimiter; Braeken, Dries

    2017-09-01

    Drug-induced cardiotoxicity poses a negative impact on public health and drug development. Cardiac safety pharmacology issues urged for the preclinical assessment of drug-induced ventricular arrhythmia leading to the design of several in vitro electrophysiological screening assays. In general, patch clamp systems allow for intracellular recordings, while multi-electrode array (MEA) technology detect extracellular activity. Here, we demonstrate a complementary metal oxide semiconductor (CMOS)-based MEA system as a reliable platform for non-invasive, long-term intracellular recording of cardiac action potentials at high resolution. Quinidine (8 concentrations from 10 -7 to 2.10 -5 M) and verapamil (7 concentrations from 10 -11 to 10 -5 M) were tested for dose-dependent responses in a network of cardiomyocytes. Electrophysiological parameters, such as the action potential duration (APD), rates of depolarization and repolarization and beating frequency were assessed. In hiPSC, quinidine prolonged APD with EC 50 of 2.2·10 -6 M. Further analysis indicated a multifactorial action potential prolongation by quinidine: (1) decreasing fast repolarization with IC 50 of 1.1·10 -6 M; (2) reducing maximum upstroke velocity with IC 50 of 2.6·10 -6 M; and (3) suppressing spontaneous activity with EC 50 of 3.8·10 -6 M. In rat neonatal cardiomyocytes, verapamil blocked spontaneous activity with EC 50 of 5.3·10 -8 M and prolonged the APD with EC 50 of 2.5·10 -8 M. Verapamil reduced rates of fast depolarization and repolarization with IC 50 s of 1.8 and 2.2·10 -7 M, respectively. In conclusion, the proposed action potential-based MEA platform offers high quality and stable long-term recordings with high information content allowing to characterize multi-ion channel blocking drugs. We anticipate application of the system as a screening platform to efficiently and cost-effectively test drugs for cardiac safety. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Early identification of hERG liability in drug discovery programs by automated patch clamp

    Directory of Open Access Journals (Sweden)

    Timm eDanker

    2014-09-01

    Full Text Available Blockade of the cardiac ion channel coded by hERG can lead to cardiac arrhythmia, which has become a major concern in drug discovery and development. Automated electrophysiological patch clamp allows assessment of hERG channel effects early in drug development to aid medicinal chemistry programs and has become routine in pharmaceutical companies. However, a number of potential sources of errors in setting up hERG channel assays by automated patch clamp can lead to misinterpretation of data or false effects being reported. This article describes protocols for automated electrophysiology screening of compound effects on the hERG channel current. Protocol details and the translation of criteria known from manual patch clamp experiments to automated patch clamp experiments to achieve good quality data are emphasized. Typical pitfalls and artifacts that may lead to misinterpretation of data are discussed. While this article focuses on hERG channel recordings using the QPatch (Sophion A/S, Copenhagen, Denmark technology, many of the assay and protocol details given in this article can be transferred for setting up different ion channel assays by automated patch clamp and are similar on other planar patch clamp platforms.

  1. The DBI action, higher-derivative supergravity, and flattening inflaton potentials

    International Nuclear Information System (INIS)

    Bielleman, Sjoerd; Ibáñez, Luis E.; 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 Dp-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 Kähler potential. We identify the supersymmetric dimension-eight operators describing the α"′ 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 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 monomial potentials.

  2. Pipe clamp effects on thin-walled pipe design

    International Nuclear Information System (INIS)

    Lindquist, M.R.

    1980-01-01

    Clamp induced stresses in FFTF piping are sufficiently large to require structural assessment. The basic principles and procedures used in analyzing FFTF piping at clamp support locations for compliance with ASME Code rules are given. Typical results from a three-dimensional shell finite element pipe model with clamp loads applied over the clamp/pipe contact area are shown. Analyses performed to categorize clamp induced piping loads as primary or secondary in nature are described. The ELCLAMP Computer Code, which performs analyses at clamp locations combining clamp induced stresses with stresses from overall piping system loads, is discussed. Grouping and enveloping methods to reduce the number of individual clamp locations requiring analysis are described

  3. The human dynamic clamp as a paradigm for social interaction.

    Science.gov (United States)

    Dumas, Guillaume; de Guzman, Gonzalo C; Tognoli, Emmanuelle; Kelso, J A Scott

    2014-09-02

    Social neuroscience has called for new experimental paradigms aimed toward real-time interactions. A distinctive feature of interactions is mutual information exchange: One member of a pair changes in response to the other while simultaneously producing actions that alter the other. Combining mathematical and neurophysiological methods, we introduce a paradigm called the human dynamic clamp (HDC), to directly manipulate the interaction or coupling between a human and a surrogate constructed to behave like a human. Inspired by the dynamic clamp used so productively in cellular neuroscience, the HDC allows a person to interact in real time with a virtual partner itself driven by well-established models of coordination dynamics. People coordinate hand movements with the visually observed movements of a virtual hand, the parameters of which depend on input from the subject's own movements. We demonstrate that HDC can be extended to cover a broad repertoire of human behavior, including rhythmic and discrete movements, adaptation to changes of pacing, and behavioral skill learning as specified by a virtual "teacher." We propose HDC as a general paradigm, best implemented when empirically verified theoretical or mathematical models have been developed in a particular scientific field. The HDC paradigm is powerful because it provides an opportunity to explore parameter ranges and perturbations that are not easily accessible in ordinary human interactions. The HDC not only enables to test the veracity of theoretical models, it also illuminates features that are not always apparent in real-time human social interactions and the brain correlates thereof.

  4. 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

  5. The Anion Paradox in Sodium Taste Reception: Resolution by Voltage-Clamp Studies

    Science.gov (United States)

    Ye, Qing; Heck, Gerard L.; Desimone, John A.

    1991-11-01

    Sodium salts are potent taste stimuli, but their effectiveness is markedly dependent on the anion, with chloride yielding the greatest response. The cellular mechanisms that mediate this phenomenon are not known. This "anion paradox" has been resolved by considering the field potential that is generated by restricted electrodiffusion of the anion through paracellular shunts between taste-bud cells. Neural responses to sodium chloride, sodium acetate, and sodium gluconate were studied while the field potential was voltage-clamped. Clamping at electronegative values eliminated the anion effect, whereas clamping at electropositive potentials exaggerated it. Thus, field potentials across the lingual epithelium modulate taste reception, indicating that the functional unit of taste reception includes the taste cell and its paracellular microenvironment.

  6. Γ-source Neutral Point Clamped Inverter

    DEFF Research Database (Denmark)

    Mo, Wei; Loh, Poh Chiang; Blaabjerg, Frede

    Transformer based Z-source inverters are recently proposed to achieve promising buck-boost capability. They have improved higher buck-boost capability, smaller size and less components count over Z-source inverters. On the other hand, neutral point clamped inverters have less switching stress...... and better output performance comparing with traditional two-level inverters. Integrating these two types of configurations can help neutral point inverters achieve enhanced votlage buck-boost capability....

  7. Analysis of the Pallet Clamping Conditions in Work Positioning

    Directory of Open Access Journals (Sweden)

    L. A. Kolesnikov

    2016-01-01

    Full Text Available Pallets of automatic transfer lines serve as the technological and work-transfer equipment. However, their design is based on the general principles of designing machine accessories. Calculation of the basic design parameters of work based on their functioning features is fairly relevant.In pallet transfer movement over work positioning there is a mismatch between axes of the basic bushing of a pallet and the clamping locks of positioning. The paper identifies the factors influencing it, and defines the conditions to ensure the trouble-free clamping lock. The circular and rhombic clamping of pallet is simultaneous. Further, a clamping load is calculated from the pallet mass (together with the work-piece and the geometric parameters of the pallet clamping.The paper reveals three movement stages of the clamping lock in a vertical plane when setting the pallet in work positioning:- a clamping lock free play till it encounters with the location bushing;- a clamping lock play length when the lead-in chamfer contacts the bushing chamfer;- a clamping lock play length over the circular surface of bushing.The study of this process has allowed us to calculate the time of pallet clamping and dynamic loads acting on the clamping lock. These calculations made it possible to calculate the required diameter of the clamping lock. The presented calculations allow a reasonable assigning the main design parameters of work positioning for the pallet automatic lines.

  8. Onset Dynamics of Action Potentials in Rat Neocortical Neurons and Identified Snail Neurons: Quantification of the Difference

    OpenAIRE

    Volgushev, Maxim; Malyshev, Aleksey; Balaban, Pavel; Chistiakova, Marina; Volgushev, Stanislav; Wolf, Fred

    2008-01-01

    The generation of action potentials (APs) is a key process in the operation of nerve cells and the communication between neurons. Action potentials in mammalian central neurons are characterized by an exceptionally fast onset dynamics, which differs from the typically slow and gradual onset dynamics seen in identified snail neurons. Here we describe a novel method of analysis which provides a quantitative measure of the onset dynamics of action potentials. This method captures the...

  9. Position-dependent patterning of spontaneous action potentials in immature cochlear inner hair cells.

    Science.gov (United States)

    Johnson, Stuart L; Eckrich, Tobias; Kuhn, Stephanie; Zampini, Valeria; Franz, Christoph; Ranatunga, Kishani M; Roberts, Terri P; Masetto, Sergio; Knipper, Marlies; Kros, Corné J; Marcotti, Walter

    2011-06-01

    Spontaneous action potential activity is crucial for mammalian sensory system development. In the auditory system, patterned firing activity has been observed in immature spiral ganglion and brain-stem neurons and is likely to depend on cochlear inner hair cell (IHC) action potentials. It remains uncertain whether spiking activity is intrinsic to developing IHCs and whether it shows patterning. We found that action potentials were intrinsically generated by immature IHCs of altricial rodents and that apical IHCs showed bursting activity as opposed to more sustained firing in basal cells. We show that the efferent neurotransmitter acetylcholine fine-tunes the IHC's resting membrane potential (V(m)), and as such is crucial for the bursting pattern in apical cells. Endogenous extracellular ATP also contributes to the V(m) of apical and basal IHCs by triggering small-conductance Ca(2+)-activated K(+) (SK2) channels. We propose that the difference in firing pattern along the cochlea instructs the tonotopic differentiation of IHCs and auditory pathway.

  10. π-Clamp-mediated cysteine conjugation

    Science.gov (United States)

    Zhang, Chi; Welborn, Matthew; Zhu, Tianyu; Yang, Nicole J.; Santos, Michael S.; van Voorhis, Troy; Pentelute, Bradley L.

    2016-02-01

    Site-selective functionalization of complex molecules is one of the most significant challenges in chemistry. Typically, protecting groups or catalysts must be used to enable the selective modification of one site among many that are similarly reactive, and general strategies that selectively tune the local chemical environment around a target site are rare. Here, we show a four-amino-acid sequence (Phe-Cys-Pro-Phe), which we call the ‘π-clamp’, that tunes the reactivity of its cysteine thiol for site-selective conjugation with perfluoroaromatic reagents. We use the π-clamp to selectively modify one cysteine site in proteins containing multiple endogenous cysteine residues. These examples include antibodies and cysteine-based enzymes that would be difficult to modify selectively using standard cysteine-based methods. Antibodies modified using the π-clamp retained binding affinity to their targets, enabling the synthesis of site-specific antibody-drug conjugates for selective killing of HER2-positive breast cancer cells. The π-clamp is an unexpected approach to mediate site-selective chemistry and provides new avenues to modify biomolecules for research and therapeutics.

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

    DEFF Research Database (Denmark)

    Henneberg, Kaj-åge; R., Plonsey

    1994-01-01

    In the paper, single-fibre models for the extracellular action potential are developed that will allow the potential to the evaluated at an arbitrary field point in the extracellular space. Fourier-domain models are restricted in that they evaluate potentials at equidistant points along a line...... parallel to the fibre axis. Consequently, they cannot easily evaluate the potential at the boundary nodes of a boundary-element electrode model. The Fourier-domain models employ axial-symmetric ring source models, and thereby provide higher accuracy that the line source model, where the source is lumped...... including anisotropy show that the spatial models require extreme care in the integration procedure owing to the singularity in the weighting functions. With adequate sampling, the spatial models can evaluate extracellular potentials with high accuracy....

  12. Application of Emergency Action Levels from Potential Release at Research Reactor HANARO

    International Nuclear Information System (INIS)

    Kim, Jongsoo; Lee, Goan Yub; Lee, Hae Choi; Kim, Bong Suk

    2014-01-01

    Execution of the protective action promptly is possible that Emergency Action Levels (EALs) must be established for a radiological release from nuclear facility. The EALs for electric power reactor are already developed and applied to recognize an emergency situation rapidly. Recently the IAEA published the safety report including the EALs for research reactor. This paper describes the EALs to apply for a potential release pathway at the research reactor HANARO. The results of table 1 and 2 will be higher than actual because the weather condition in real situation is difference. However, the EALs applying the potential stack release, ground release and site can be useful for research reactor HANARO making the emergency declaration. The EALs at the site boundary of the table 3 can be applied to protect the off-site public

  13. The monophasic action potential upstroke: a means of characterizing local conduction.

    Science.gov (United States)

    Levine, J H; Moore, E N; Kadish, A H; Guarnieri, T; Spear, J F

    1986-11-01

    The upstrokes of monophasic action potentials (MAPs) recorded with an extracellular pressure electrode were characterized in isolated canine tissue preparations in vitro. The characteristics of the MAP upstroke were compared with those of the local action potential foot as well as with the characteristics of approaching electrical activation during uniform and asynchronous conduction. The upstroke of the MAP was exponential during uniform conduction. The time constant of rise of the MAP upstroke (TMAP) correlated with that of the action potential foot (Tfoot): TMAP + 1.01 Tfoot + 0.50; r2 = .80. Furthermore, changes in Tfoot with alterations in cycle length were associated with similar changes in TMAP: Tfoot = 1.06 TMAP - 0.11; r2 = .78. In addition, TMAP and Tfoot both deviated from exponential during asynchronous activation; the inflections that developed in the MAP upstroke correlated in time with intracellular action potential upstrokes that were asynchronous in onset in these tissues. Finally, the field of view of the MAP was determined and was found to be dependent in part on tissue architecture and the space constant. Specifically, the field of view of the MAP was found to be greater parallel compared with transverse to fiber orientation (6.02 +/- 1.74 vs 3.03 +/- 1.10 mm; p less than .01). These data suggest that the MAP upstroke may be used to define and characterize local electrical activation. The relatively large field of view of the MAP suggests that this technique may be a sensitive means to record focal membrane phenomena in vivo.

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

    Science.gov (United States)

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

    2017-11-01

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

  15. The plastic instability of clamped-clamped conical thin-walled pipe reducers

    International Nuclear Information System (INIS)

    Awad, Ibrahim; Saleh, Ch.A.R.; Ragab, A.R.

    2016-01-01

    The analytical study for plastic deformation of clamped–clamped conical reducer pipe under internal pressure does not deduce a closed form expression for the pressure at plastic instability. The presented study employs finite element analysis (FEA) to estimate the internal pressure at instability for conical reducers made of different materials and having different dimensional configurations. Forty dimensional configurations, classified as medium type, and five types of materials have been included in the analysis using ABAQUS package. A correlation expression is derived by nonlinear regression to predict the instability pressure. The proposed expression is verified for other dimensional configurations out of the above used forty models and for other materials. Experiments have been conducted by pressurizing conical clamped-clamped reducers until bursting in order to verify the finite element models. Comparison of instability pressures, strains and deflections at specific points along the conical surface shows satisfactory agreement between analysis and experiments. - Highlights: • This study offers a parametric study of the plastic instability pressure of clamped-clamped conical reducers. • A closed form analytical expression for the instability pressure is derived by using nonlinear regression. • The finite element analysis is validated by conducting bursting tests.

  16. Action potential-independent and pharmacologically unique vesicular serotonin release from dendrites

    Science.gov (United States)

    Colgan, Lesley A.; Cavolo, Samantha L.; Commons, Kathryn G.; Levitan, Edwin S.

    2012-01-01

    Serotonin released within the dorsal raphe nucleus (DR) induces feedback inhibition of serotonin neuron activity and consequently regulates mood-controlling serotonin release throughout the forebrain. Serotonin packaged in vesicles is released in response to action potentials by the serotonin neuron soma and terminals, but the potential for release by dendrites is unknown. Here three-photon (3P) microscopy imaging of endogenous serotonin in living rat brain slice, immunofluorescence and immuno-gold electron microscopy detection of VMAT2 (vesicular monoamine transporter 2) establish the presence of vesicular serotonin within DR dendrites. Furthermore, activation of glutamate receptors is shown to induce vesicular serotonin release from dendrites. However, unlike release from the soma and terminals, dendritic serotonin release is independent of action potentials, relies on L-type Ca2+ channels, is induced preferentially by NMDA, and displays distinct sensitivity to the selective serotonin reuptake inhibitor (SSRI) antidepressant fluoxetine. The unique control of dendritic serotonin release has important implications for DR physiology and the antidepressant action of SSRIs, dihydropyridines and NMDA receptor antagonists. PMID:23136413

  17. Automated grouping of action potentials of human embryonic stem cell-derived cardiomyocytes.

    Science.gov (United States)

    Gorospe, Giann; Zhu, Renjun; Millrod, Michal A; Zambidis, Elias T; Tung, Leslie; Vidal, Rene

    2014-09-01

    Methods for obtaining cardiomyocytes from human embryonic stem cells (hESCs) are improving at a significant rate. However, the characterization of these cardiomyocytes (CMs) is evolving at a relatively slower rate. In particular, there is still uncertainty in classifying the phenotype (ventricular-like, atrial-like, nodal-like, etc.) of an hESC-derived cardiomyocyte (hESC-CM). While previous studies identified the phenotype of a CM based on electrophysiological features of its action potential, the criteria for classification were typically subjective and differed across studies. In this paper, we use techniques from signal processing and machine learning to develop an automated approach to discriminate the electrophysiological differences between hESC-CMs. Specifically, we propose a spectral grouping-based algorithm to separate a population of CMs into distinct groups based on the similarity of their action potential shapes. We applied this method to a dataset of optical maps of cardiac cell clusters dissected from human embryoid bodies. While some of the nine cell clusters in the dataset are presented with just one phenotype, the majority of the cell clusters are presented with multiple phenotypes. The proposed algorithm is generally applicable to other action potential datasets and could prove useful in investigating the purification of specific types of CMs from an electrophysiological perspective.

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

    Science.gov (United States)

    Un, M Kerem; Kaghazchi, Hamed

    2018-01-01

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

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

    Science.gov (United States)

    Bahar, Entaz; Kim, Hyongsuk; Yoon, Hyonok

    2016-09-15

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

  20. Multilevel-clamped multilevel converters (MLC2)

    DEFF Research Database (Denmark)

    Rodriguez, Pedro; Bellar, Maria Dias; Muñoz-Aguliar, Raúl Santiago

    2012-01-01

    clamping scheme is the ML clamping cell, which is composed of a pair of dc sources associated with one single-pole/triple-throw type of switch arrangement. The number of series-connected ML-clamping cells will set the number of levels of the synthesized waveform. By depending on the MCU arrangements......, different converter configurations can be derived, namely, the common clamping and the modular types. Both approaches can be accomplished by employing classical three-level neutral-point-clamped (NPC) technology. Thus, the overall structure of the resultant converter is kept simple, wherein the number...

  1. [Analysis of brain hemometabolism behavior during carotid endarterectomy with temporary clamping.].

    Science.gov (United States)

    Duval Neto, Gastão Fernandes; Niencheski, Augusto H

    2004-04-01

    Carotid endarterectomy with temporary clamping changes cerebral blood flow and cerebral metabolic oxygen demand ratio with consequent oligemic hypoxia or hemometabolic uncoupling. This study aimed at identifying changes in brain hemometabolism, evaluated through changes in oxyhemoglobin saturation in internal jugular vein bulb (SvjO2) during carotid endarterectomy with clamping, and at correlating these changes with potentially interfering factors, mainly end tidal CO2 pressure (P ET CO2) and cerebral perfusion pressure (CPP). Sixteen patients with unilateral carotid stenotic disease scheduled to carotid endarterectomy with carotid arterial clamping were enrolled in this study. Parameters including internal jugular bulb oxyhemoglobin saturation, stump pressure and end tidal CO2 pressure were measured at the following moments: M1 - pre-clamping; M2 - 3 minutes after clamping; M3 - pre-unclamping; M4 - post-unclamping). The comparison among SvjO2 (%, mean +/- SD) in all studied periods has shown differences between those recorded in moments M1 (52.25 +/- 7.87) and M2 (47.43 +/- 9.19). This initial decrease stabilized during temporary clamping, showing decrease in the comparison between M2 and M3 (46.56 +/- 9.25), without statistical significance (p = ns). At post-unclamping, M4 (47.68 +/- 9.12), SvjO2 was increased as compared to M2 and M3 clamping stages, however it was still lower than that of pre-clamping stage M1.(M4 x M1 - p brain hemometabolic uncoupling trend were correlated to P ET CO2. The comparison between CPP and SvjO2 showed weak correlation devoid of statistical significance. In the conditions of our study, SvjO2 measurement is a fast and effective way of clinically monitoring changes in CBF/CMRO2 ratio. Temporary carotid clamping implies in a trend towards brain hemometabolic uncoupling and, as a consequence, to oligemic ischemia; cerebral perfusion pressure does not assesses brain hemometabolic status (CBF and CMRO2 ratio); hypocapnia, may lead to

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

    Science.gov (United States)

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

    2016-11-01

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

  3. 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.

  4. 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.

  5. 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.

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

    Science.gov (United States)

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

    2011-04-04

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

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

    Science.gov (United States)

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

    2011-01-01

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

  8. Biological cell controllable patch-clamp microchip

    Science.gov (United States)

    Penmetsa, Siva; Nagrajan, Krithika; Gong, Zhongcheng; Mills, David; Que, Long

    2010-12-01

    A patch-clamp (PC) microchip with cell sorting and positioning functions is reported, which can avoid drawbacks of random cell selection or positioning for a PC microchip. The cell sorting and positioning are enabled by air bubble (AB) actuators. AB actuators are pneumatic actuators, in which air pressure is generated by microheaters within sealed microchambers. The sorting, positioning, and capturing of 3T3 cells by this type of microchip have been demonstrated. Using human breast cancer cells MDA-MB-231 as the model, experiments have been demonstrated by this microchip as a label-free technical platform for real-time monitoring of the cell viability.

  9. Bingham Sealing and Application in Vacuum Clamping

    Science.gov (United States)

    Yao, S. M.; Teo, Wee Kin; Geng, Zunmin; Turner, Sam; Ridgway, Keith

    2011-12-01

    Vacuum clamping is extensively used in shell machining. In this paper a Bingham Sealing (BS) is presented and formulized based on Bingham plastic performance. The sealing capability of BS is evaluated in various cases. A new Bingham plastic is developed and the yield stress is measured. The performances of "O"ring sealing and BS with the developed Bingham plastic are compared to the static experiment. In this experiment the same vacuum is achieved and the distortion of the blade with BS is better than that with "O" ring sealing.

  10. Bingham Sealing and Application in Vacuum Clamping

    International Nuclear Information System (INIS)

    Yao, S M; Teo, Wee Kin; Geng Zunmin; Turner, Sam; Ridgway, Keith

    2011-01-01

    Vacuum clamping is extensively used in shell machining. In this paper a Bingham Sealing (BS) is presented and formulized based on Bingham plastic performance. The sealing capability of BS is evaluated in various cases. A new Bingham plastic is developed and the yield stress is measured. The performances of Or ing sealing and BS with the developed Bingham plastic are compared to the static experiment. In this experiment the same vacuum is achieved and the distortion of the blade with BS is better than that with 'O' ring sealing.

  11. A Hybrid Model for Safety Pharmacology on an Automated Patch Clamp Platform: Using Dynamic Clamp to Join iPSC-Derived Cardiomyocytes and Simulations of Ik1 Ion Channels in Real-Time

    Directory of Open Access Journals (Sweden)

    Birgit Goversen

    2018-01-01

    Full Text Available An important aspect of the Comprehensive In Vitro Proarrhythmia Assay (CiPA proposal is the use of human stem cell-derived cardiomyocytes and the confirmation of their predictive power in drug safety assays. The benefits of this cell source are clear; drugs can be tested in vitro on human cardiomyocytes, with patient-specific genotypes if needed, and differentiation efficiencies are generally excellent, resulting in a virtually limitless supply of cardiomyocytes. There are, however, several challenges that will have to be surmounted before successful establishment of hSC-CMs as an all-round predictive model for drug safety assays. An important factor is the relative electrophysiological immaturity of hSC-CMs, which limits arrhythmic responses to unsafe drugs that are pro-arrhythmic in humans. Potentially, immaturity may be improved functionally by creation of hybrid models, in which the dynamic clamp technique joins simulations of lacking cardiac ion channels (e.g., IK1 with hSC-CMs in real-time during patch clamp experiments. This approach has been used successfully in manual patch clamp experiments, but throughput is low. In this study, we combined dynamic clamp with automated patch clamp of iPSC-CMs in current clamp mode, and demonstrate that IK1 conductance can be added to iPSC-CMs on an automated patch clamp platform, resulting in an improved electrophysiological maturity.

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

    Science.gov (United States)

    Pearman, Charles M.

    2014-01-01

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

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

    Science.gov (United States)

    Pearman, Charles M

    2014-12-01

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

  14. Voltage Gated Calcium Channel Activation by Backpropagating Action Potentials Downregulates NMDAR Function

    Directory of Open Access Journals (Sweden)

    Anne-Kathrin Theis

    2018-04-01

    Full Text Available The majority of excitatory synapses are located on dendritic spines of cortical glutamatergic neurons. In spines, compartmentalized Ca2+ signals transduce electrical activity into specific long-term biochemical and structural changes. Action potentials (APs propagate back into the dendritic tree and activate voltage gated Ca2+ channels (VGCCs. For spines, this global mode of spine Ca2+ signaling is a direct biochemical feedback of suprathreshold neuronal activity. We previously demonstrated that backpropagating action potentials (bAPs result in long-term enhancement of spine VGCCs. This activity-dependent VGCC plasticity results in a large interspine variability of VGCC Ca2+ influx. Here, we investigate how spine VGCCs affect glutamatergic synaptic transmission. We combined electrophysiology, two-photon Ca2+ imaging and two-photon glutamate uncaging in acute brain slices from rats. T- and R-type VGCCs were the dominant depolarization-associated Ca2+conductances in dendritic spines of excitatory layer 2 neurons and do not affect synaptic excitatory postsynaptic potentials (EPSPs measured at the soma. Using two-photon glutamate uncaging, we compared the properties of glutamatergic synapses of single spines that express different levels of VGCCs. While VGCCs contributed to EPSP mediated Ca2+ influx, the amount of EPSP mediated Ca2+ influx is not determined by spine VGCC expression. On a longer timescale, the activation of VGCCs by bAP bursts results in downregulation of spine NMDAR function.

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

    Science.gov (United States)

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

    2017-10-01

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

  16. Outcome producing potential influences twelve-month-olds' interpretation of a novel action as goal-directed.

    Science.gov (United States)

    Biro, Szilvia; Verschoor, Stephan; Coalter, Esther; Leslie, Alan M

    2014-11-01

    Learning about a novel, goal-directed action is a complex process. It requires identifying the outcome of the action and linking the action to its outcome for later use in new situations to predict the action or to anticipate its outcome. We investigated the hypothesis that linking a novel action to a salient change in the environment is critical for infants to assign a goal to the novel action. We report a study in which we show that 12-month-old infants, who were provided with prior experience with a novel action accompanied with a salient visible outcome in one context, can interpret the same action as goal-directed even in the absence of the outcome in another context. Our control condition shows that prior experience with the action, but without the salient effect, does not lead to goal-directed interpretation of the novel action. We also found that, for the case of 9-month-olds infants, prior experience with the outcome producing potential of the novel action does not facilitate a goal-directed interpretation of the action. However, this failure was possibly due to difficulties with generalizing the learnt association to another context rather than with linking the action to its outcome. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Single K ATP channel opening in response to action potential firing in mouse dentate granule neurons.

    Science.gov (United States)

    Tanner, Geoffrey R; Lutas, Andrew; Martínez-François, Juan Ramón; Yellen, Gary

    2011-06-08

    ATP-sensitive potassium channels (K(ATP) channels) are important sensors of cellular metabolic state that link metabolism and excitability in neuroendocrine cells, but their role in nonglucosensing central neurons is less well understood. To examine a possible role for K(ATP) channels in modulating excitability in hippocampal circuits, we recorded the activity of single K(ATP) channels in cell-attached patches of granule cells in the mouse dentate gyrus during bursts of action potentials generated by antidromic stimulation of the mossy fibers. Ensemble averages of the open probability (p(open)) of single K(ATP) channels over repeated trials of stimulated spike activity showed a transient increase in p(open) in response to action potential firing. Channel currents were identified as K(ATP) channels through blockade with glibenclamide and by comparison with recordings from Kir6.2 knock-out mice. The transient elevation in K(ATP) p(open) may arise from submembrane ATP depletion by the Na(+)-K(+) ATPase, as the pump blocker strophanthidin reduced the magnitude of the elevation. Both the steady-state and stimulus-elevated p(open) of the recorded channels were higher in the presence of the ketone body R-β-hydroxybutyrate, consistent with earlier findings that ketone bodies can affect K(ATP) activity. Using perforated-patch recording, we also found that K(ATP) channels contribute to the slow afterhyperpolarization following an evoked burst of action potentials. We propose that activity-dependent opening of K(ATP) channels may help granule cells act as a seizure gate in the hippocampus and that ketone-body-mediated augmentation of the activity-dependent opening could in part explain the effect of the ketogenic diet in reducing epileptic seizures.

  18. 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.

  19. Control of clustered action potential firing in a mathematical model of entorhinal cortex stellate cells.

    Science.gov (United States)

    Tait, Luke; Wedgwood, Kyle; Tsaneva-Atanasova, Krasimira; Brown, Jon T; Goodfellow, Marc

    2018-07-14

    The entorhinal cortex is a crucial component of our memory and spatial navigation systems and is one of the first areas to be affected in dementias featuring tau pathology, such as Alzheimer's disease and frontotemporal dementia. Electrophysiological recordings from principle cells of medial entorhinal cortex (layer II stellate cells, mEC-SCs) demonstrate a number of key identifying properties including subthreshold oscillations in the theta (4-12 Hz) range and clustered action potential firing. These single cell properties are correlated with network activity such as grid firing and coupling between theta and gamma rhythms, suggesting they are important for spatial memory. As such, experimental models of dementia have revealed disruption of organised dorsoventral gradients in clustered action potential firing. To better understand the mechanisms underpinning these different dynamics, we study a conductance based model of mEC-SCs. We demonstrate that the model, driven by extrinsic noise, can capture quantitative differences in clustered action potential firing patterns recorded from experimental models of tau pathology and healthy animals. The differential equation formulation of our model allows us to perform numerical bifurcation analyses in order to uncover the dynamic mechanisms underlying these patterns. We show that clustered dynamics can be understood as subcritical Hopf/homoclinic bursting in a fast-slow system where the slow sub-system is governed by activation of the persistent sodium current and inactivation of the slow A-type potassium current. In the full system, we demonstrate that clustered firing arises via flip bifurcations as conductance parameters are varied. Our model analyses confirm the experimentally suggested hypothesis that the breakdown of clustered dynamics in disease occurs via increases in AHP conductance. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Action potential propagation recorded from single axonal arbors using multi-electrode arrays.

    Science.gov (United States)

    Tovar, Kenneth R; Bridges, Daniel C; Wu, Bian; Randall, Connor; Audouard, Morgane; Jang, Jiwon; Hansma, Paul K; Kosik, Kenneth S

    2018-04-11

    We report the presence of co-occurring extracellular action potentials (eAPs) from cultured mouse hippocampal neurons among groups of planar electrodes on multi-electrode arrays (MEAs). The invariant sequences of eAPs among co-active electrode groups, repeated co-occurrences and short inter-electrode latencies are consistent with action potential propagation in unmyelinated axons. Repeated eAP co-detection by multiple electrodes was widespread in all our data records. Co-detection of eAPs confirms they result from the same neuron and allows these eAPs to be isolated from all other spikes independently of spike sorting algorithms. We averaged co-occurring events and revealed additional electrodes with eAPs that would otherwise be below detection threshold. We used these eAP cohorts to explore the temperature sensitivity of action potential propagation and the relationship between voltage-gated sodium channel density and propagation velocity. The sequence of eAPs among co-active electrodes 'fingerprints' neurons giving rise to these events and identifies them within neuronal ensembles. We used this property and the non-invasive nature of extracellular recording to monitor changes in excitability at multiple points in single axonal arbors simultaneously over several hours, demonstrating independence of axonal segments. Over several weeks, we recorded changes in inter-electrode propagation latencies and ongoing changes in excitability in different regions of single axonal arbors. Our work illustrates how repeated eAP co-occurrences can be used to extract physiological data from single axons with low electrode density MEAs. However, repeated eAP co-occurrences leads to over-sampling spikes from single neurons and thus can confound traditional spike-train analysis.

  1. Implementation of a fast 16-Bit dynamic clamp using LabVIEW-RT.

    Science.gov (United States)

    Kullmann, Paul H M; Wheeler, Diek W; Beacom, Joshua; Horn, John P

    2004-01-01

    The dynamic-clamp method provides a powerful electrophysiological tool for creating virtual ionic conductances in living cells and studying their influence on membrane potential. Here we describe G-clamp, a new way to implement a dynamic clamp using the real-time version of the Lab-VIEW programming environment together with a Windows host, an embedded microprocessor that runs a real-time operating system and a multifunction data-acquisition board. The software includes descriptions of a fast voltage-dependent sodium conductance, delayed rectifier, M-type and A-type potassium conductances, and a leak conductance. The system can also read synaptic conductance waveforms from preassembled data files. These virtual conductances can be reliably implemented at speeds < or =43 kHz while simultaneously saving two channels of data with 16-bit precision. G-clamp also includes utilities for measuring current-voltage relations, synaptic strength, and synaptic gain. Taking an approach built on a commercially available software/hardware platform has resulted in a system that is easy to assemble and upgrade. In addition, the graphical programming structure of LabVIEW should make it relatively easy for others to adapt G-clamp for new experimental applications.

  2. Conduction velocity of action potentials measured from unidimensional latency-topography in human and frog skeletal muscle fibers.

    Science.gov (United States)

    Homma, S; Nakajima, Y; Hayashi, K; Toma, S

    1986-01-01

    Conduction of an action potential along skeletal muscle fibers was graphically displayed by unidimensional latency-topography, UDLT. Since the slopes of the equipotential line were linear and the width of the line was constant, it was possible to calculate conduction velocity from the slope. To determine conduction direction of the muscle action potential elicited by electric stimulation applied directly to the muscle, surface recording electrodes were placed on a two-dimensional plane over a human muscle. Thus a bi-dimensional topography was obtained. Then, twelve or sixteen surface electrodes were placed linearly along the longitudinal direction of the action potential conduction which was disclosed by the bi-dimensional topography. Thus conduction velocity of muscle action potential in man, calculated from the slope, was for m. brachioradialis, 3.9 +/- 0.4 m/s; for m. biceps brachii, 3.6 +/- 0.2 m/s; for m. sternocleidomastoideus, 3.6 +/- 0.4 m/s. By using a tungsten microelectrode to stimulate the motor axons, a convex-like equipotential line of an action potential in UDLT was obtained from human muscle fibers. Since a similar pattern of UDLT was obtained from experiments on isolated frog muscles, in which the muscle action potential was elicited by stimulating the motor axon, it was assumed that the maximum of the curve corresponds to the end-plate region, and that the slopes on both sides indicate bi-directional conduction of the action potential.

  3. 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.

  4. Ionization from short-range potential under action of electromagnetic field of complex configuration

    CERN Document Server

    Rodionov, V N; Kravtsova, G A

    2002-01-01

    The transcendental equation for the complex energy is obtained on the basis of the exactly solvable 3D model of the short-acting potential and the Green time function in the intensive electromagnetic field, constituting the combination of the constant magnetic field and the circular-polarization wave field. The electron quasistationary states parameters in the delta-potential with an account of the action of the intensive external field of complex configuration are calculated. The problem on the possibility of stabilizing the bound states decay of the spinor and scalar particles through the intensive magnetic field is clarified. It is established that the obtained results regime the reexamination of the accepted notion on the stabilizing role of the strong magnetic field by the atoms ionization

  5. 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...... + 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...

  6. Traditional Japanese medicines inhibit compound action potentials in the frog sciatic nerve.

    Science.gov (United States)

    Matsushita, Akitomo; Fujita, Tsugumi; Ohtsubo, Sena; Kumamoto, Eiichi

    2016-02-03

    Traditional Japanese (Kampo) medicines have a variety of clinical effects including pain alleviation, but evidence for a mechanism for their pain relief has not yet been elucidated fully. Considering that Kampo medicine contains many plant-derived chemicals having an ability to inhibit nerve action potential conduction, it is possible that this medicine inhibits nerve conduction. The purpose of the present study was to know how various Kampo medicines affect nerve conduction. We examined the effects of Kampo and crude medicines on compound action potentials (CAPs) recorded from the frog sciatic nerve by using the air-gap method. Daikenchuto, rikkosan, kikyoto, rikkunshito, shakuyakukanzoto and kakkonto concentration-dependently reduced the peak amplitude of the CAP. Among the Kampo medicines, daikenchuto was the most effective in inhibiting CAPs. Daikenchuto is composed of three kinds of crude medicine, Japanese pepper, processed ginger and ginseng radix. When the crude medicines were tested, Japanese pepper and processed ginger reduced CAP peak amplitudes, while ginseng radix hardly affected CAPs. Moreover, there was an interaction between the Japanese pepper and processed ginger activities in such that one medicine at low but not high concentrations increased the extent of the inhibition by the other one that was co-applied. Kampo medicines have an ability to inhibit nerve conduction. This action of daikenchuto is due to Japanese pepper and processed ginger but not ginseng radix, probably through an interaction between Japanese pepper and processed ginger in a manner dependent on their concentrations. Nerve conduction inhibition could contribute to at least a part of Kampo medicine's clinical effects such as pain alleviation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. 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.

  8. Biophysical foundations for the study of the electrical excitability and action potential propagation in myocardium

    International Nuclear Information System (INIS)

    Suarez Antola, R.

    1991-01-01

    The electric current flow in the heterogeneous and anysotropic volume conductor of the myocardium is studied. The equations of bidomain theory are derived using an approach framed in the theory of averaged fields, introducing microscopic, mesoscopic and macroscopic spatial scales. However, the procedure, compatible with the histological and the anatomical details of the organ, is different from the multiple scale asymptotic expansions usually applied in homogeneization problems. A probabilistic approach framed in large numbers theorems is used to derive the equation for membrane ionic current from the stochastic activity of the channels at the microscopic level. An operational procedure suitable to define a sharp bidomain boundary from the fuzzy distribution of structural details and physical properties at the histological level is given. The problem of threshold is studied. The sizes and shapes of critical masses of cardiac cells that must be depolarized above threshold in order to produce a propagated action potential are determined by an approximate analytical procedure. The concept of family of threshold patterns for the emergence of action potentials in the heart is introduced. This concept is applied to discuss the conditions of emergence of ectopic focus. Analytical formulae are derived, for the time constant and the rheobase for electrical stimulation of the myocardium. These formulae are in good agreement with known experimental results. New experiments that could be done to confirm or reject them are suggested

  9. The effect of recording site on extracted features of motor unit action potential.

    Science.gov (United States)

    Artuğ, N Tuğrul; Goker, Imran; Bolat, Bülent; Osman, Onur; Kocasoy Orhan, Elif; Baslo, M Baris

    2016-06-01

    Motor unit action potential (MUAP), which consists of individual muscle fiber action potentials (MFAPs), represents the electrical activity of the motor unit. The values of the MUAP features are changed by denervation and reinnervation in neurogenic involvement as well as muscle fiber loss with increased diameter variability in myopathic diseases. The present study is designed to investigate how increased muscle fiber diameter variability affects MUAP parameters in simulated motor units. In order to detect this variation, simulated MUAPs were calculated both at the innervation zone where the MFAPs are more synchronized, and near the tendon, where they show increased temporal dispersion. Reinnervation in neurogenic state increases MUAP amplitude for the recordings at both the innervation zone and near the tendon. However, MUAP duration and the number of peaks significantly increased in a case of myopathy for recordings near the tendon. Furthermore, of the new features, "number of peaks×spike duration" was found as the strongest indicator of MFAP dispersion in myopathy. MUAPs were also recorded from healthy participants in order to investigate the biological counterpart of the simulation data. MUAPs which were recorded near to tendon revealed significantly prolonged duration and decreased amplitude. Although the number of peaks was increased by moving the needle near to tendon, this was not significant. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

    Science.gov (United States)

    Abouelela, Ahmed; Wieraszko, Andrzej

    2016-01-01

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

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

    Science.gov (United States)

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

    2017-10-01

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

  12. Diuretic response to acute hypertension is blunted during angiotensin II clamp

    DEFF Research Database (Denmark)

    Leong, Patrick K K; Zhang, Yibin; Yang, Li E

    2002-01-01

    and endogenous lithium clearance increased two- and threefold, respectively. We conclude that HOE-140, an inhibitor of the B(2) receptor, potentiates the sensitivity of arterial pressure to ANG II and that clamping systemic ANG II levels during acute hypertension blunts the magnitude of the pressure diuretic...

  13. Patch-clamp recordings of rat neurons from acute brain slices of the somatosensory cortex during magnetic stimulation.

    Science.gov (United States)

    Pashut, Tamar; Magidov, Dafna; Ben-Porat, Hana; Wolfus, Shuki; Friedman, Alex; Perel, Eli; Lavidor, Michal; Bar-Gad, Izhar; Yeshurun, Yosef; Korngreen, Alon

    2014-01-01

    Although transcranial magnetic stimulation (TMS) is a popular tool for both basic research and clinical applications, its actions on nerve cells are only partially understood. We have previously predicted, using compartmental modeling, that magnetic stimulation of central nervous system neurons depolarized the soma followed by initiation of an action potential in the initial segment of the axon. The simulations also predict that neurons with low current threshold are more susceptible to magnetic stimulation. Here we tested these theoretical predictions by combining in vitro patch-clamp recordings from rat brain slices with magnetic stimulation and compartmental modeling. In agreement with the modeling, our recordings demonstrate the dependence of magnetic stimulation-triggered action potentials on the type and state of the neuron and its orientation within the magnetic field. Our results suggest that the observed effects of TMS are deeply rooted in the biophysical properties of single neurons in the central nervous system and provide a framework both for interpreting existing TMS data and developing new simulation-based tools and therapies.

  14. Patch-clamp recordings of rat neurons from acute brain slices of the somatosensory cortex during magnetic stimulation

    Directory of Open Access Journals (Sweden)

    Tamar ePashut

    2014-06-01

    Full Text Available Although transcranial magnetic stimulation (TMS is a popular tool for both basic research and clinical applications, its actions on nerve cells are only partially understood. We have previously predicted, using compartmental modeling, that magnetic stimulation of central nervous system neurons depolarized the soma followed by initiation of an action potential in the initial segment of the axon. The simulations also predict that neurons with low current threshold are more susceptible to magnetic stimulation. Here we tested these theoretical predictions by combining in vitro patch-clamp recordings from rat brain slices with magnetic stimulation and compartmental modeling. In agreement with the modeling, our recordings demonstrate the dependence of magnetic stimulation-triggered action potentials on the type and state of the neuron and its orientation within the magnetic field. Our results suggest that the observed effects of TMS are deeply rooted in the biophysical properties of single neurons in the central nervous system and provide a framework both for interpreting existing TMS data and developing new simulation-based tools and therapies.

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

    Directory of Open Access Journals (Sweden)

    Philip Gemmell

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2003-01-01

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

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

    Science.gov (United States)

    Adult Learning, 2012

    2012-01-01

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

  19. Reducing blood loss during laparoscopic myomectomy by temporary uterine artery clamping using bulldog clamp

    Directory of Open Access Journals (Sweden)

    Kai-Jo Chiang

    2014-01-01

    Full Text Available Uterine myoma is the most common benign gynecologic tumor worldwide. Mini-invasive surgery has become popular for myomectomy, with advantages over laparotomy. However, reducing blood loss during laparoscopic myomectomy is a major concern for the surgeon because of the limitation in making a quick control bleeding during the operation. Several methods have proved to decrease blood flow, but are not always effective or available. We present a case of uterine myoma with the uterine arteries clamped by bulldog clamps during laparoscopic myomectomy. The myoma was removed successfully with minimal blood loss (<50 ml during the operation. This is an effective, safe, and reliable method for reducing bleeding during laparoscopic myomectomy that does not require ligation of the uterine artery.

  20. Electrophysiologic evaluation of lumbosacral single nerve roots using compound muscle action potentials.

    Science.gov (United States)

    Ogura, Taku; Shikata, Hideto; Hase, Hitoshi; Mori, Masaki; Hayashida, Taturo; Osawa, Toru; Mikami, Yasuo; Kubo, Toshikazu

    2003-10-01

    Transcutaneous electrical stimulation applied to the vertebral column produces compound muscle action potentials (CMAPs) from the leg muscles. Using this method, we evaluated the efferent pathways of the lumbosacral nerve roots. The subjects were 26 healthy volunteers and 31 patients with lumbar disc herniation (LDH). CMAP recordings were obtained from the bilateral vastus medialis, tibialis anterior, extensor digitorum brevis, and abductor hallucis muscles using low-output-impedance stimulation. In normal subjects, the CMAP latency increased linearly with the distance between the stimulating electrode and the recording electrode, with little difference in latency between the left and the right sides in each subject. The CMAP amplitude was significantly lower in the patients with LDH, and the latency was also prolonged when the stimulating electrode was placed above the lesion. This technique may thus be a useful noninvasive method for assessing lumbosacral nerve root function in patients with LDH.

  1. Sensory nerve action potentials and sensory perception in women with arthritis of the hand.

    Science.gov (United States)

    Calder, Kristina M; Martin, Alison; Lydiate, Jessica; MacDermid, Joy C; Galea, Victoria; MacIntyre, Norma J

    2012-05-10

    Arthritis of the hand can limit a person's ability to perform daily activities. Whether or not sensory deficits contribute to the disability in this population remains unknown. The primary purpose of this study was to determine if women with osteoarthritis (OA) or rheumatoid arthritis (RA) of the hand have sensory impairments. Sensory function in the dominant hand of women with hand OA or RA and healthy women was evaluated by measuring sensory nerve action potentials (SNAPs) from the median, ulnar and radial nerves, sensory mapping (SM), and vibratory and current perception thresholds (VPT and CPT, respectively) of the second and fifth digits. All SNAP amplitudes were significantly lower for the hand OA and hand RA groups compared with the healthy group (p sensory fibers in the median, ulnar and radial nerves. Less apparent were losses in conduction speed or sensory perception.

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

    Directory of Open Access Journals (Sweden)

    Wentao Li

    2016-08-01

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

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

    CERN Document Server

    Hu, H P

    2004-01-01

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

  4. Sensory action potentials of the maxillary nerve: a methodologic study with clinical implications

    DEFF Research Database (Denmark)

    Thygesen, Torben; Baad-Hansen, Lene; Svensson, Peter

    2009-01-01

    PURPOSE: Recently, recording of sensory nerve action potentials (SNAPs) of the inferior alveolar nerve (IAN) was described and is used as a diagnostic test of traumatic neuropathic trigeminal disorders. The technique is limited to IAN damage; therefore, we adapted the technique to the maxillary...... nerve, which is also frequently injured by either trauma or orthognathic surgery. PATIENTS AND METHODS: Fourteen healthy volunteers participated in this methodologic study in which the infraorbital nerve (ION) was stimulated with 2 needle electrodes. The SNAPs were recorded from the maxillary nerve...... difference. Repeated tests within a session test demonstrated no significant differences in the latency data (ANOVA: P= .225) or amplitude data (ANOVA: P= .44). Stimulus-response curves indicated that the SNAPs saturated at 5.1+/-4.4 mA stimulus intensity. In 1 subject, stimulation of the mental nerve...

  5. In-vitro characterization of a cochlear implant system for recording of evoked compound action potentials

    Science.gov (United States)

    2012-01-01

    Background Modern cochlear implants have integrated recording systems for measuring electrically evoked compound action potentials of the auditory nerve. The characterization of such recording systems is important for establishing a reliable basis for the interpretation of signals acquired in vivo. In this study we investigated the characteristics of the recording system integrated into the MED-EL PULSARCI100 cochlear implant, especially its linearity and resolution, in order to develop a mathematical model describing the recording system. Methods In-vitro setup: The cochlear implant, including all attached electrodes, was fixed in a tank of physiologic saline solution. Sinusoidal signals of the same frequency but with different amplitudes were delivered via a signal generator for measuring and recording on a single electrode. Computer simulations: A basic mathematical model including the main elements of the recording system, i.e. amplification and digitalization stage, was developed. For this, digital output for sinusoidal input signals of different amplitudes were calculated using in-vitro recordings as reference. Results Using an averaging of 100 measurements the recording system behaved linearly down to approximately -60 dB of the input signal range. Using the same method, a system resolution of 10 μV was determined for sinusoidal signals. The simulation results were in very good agreement with the results obtained from in-vitro experiments. Conclusions The recording system implemented in the MED-EL PULSARCI100 cochlear implant for measuring the evoked compound action potential of the auditory nerve operates reliably. The developed mathematical model provides a good approximation of the recording system. PMID:22531599

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

    Directory of Open Access Journals (Sweden)

    Jack Kent

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

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

    Science.gov (United States)

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

    2017-09-27

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

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

    Science.gov (United States)

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

    2018-01-01

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

  9. Evaluation of clamp effects on LMFBR piping systems

    International Nuclear Information System (INIS)

    Jones, G.L.

    1980-01-01

    Loop-type liquid metal breeder reactor plants utilize thin-wall piping to mitigate through-wall thermal gradients due to rapid thermal transients. These piping loops require a support system to carry the combined weight of the pipe, coolant and insulation and to provide attachments for seismic restraints. The support system examined here utilizes an insulated pipe clamp designed to minimize the stresses induced in the piping. To determine the effect of these clamps on the pipe wall a non-linear, two-dimensional, finite element model of the clamp, insulation and pipe wall was used to determine the clamp/pipe interface load distributions which were then applied to a three-dimensional, finite element model of the pipe. The two-dimensional interaction model was also utilized to estimate the combined clamp/pipe stiffness

  10. 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

  11. Action potentials and ion conductances in wild-type and CALHM1-knockout type II taste cells

    Science.gov (United States)

    Saung, Wint Thu; Foskett, J. Kevin

    2017-01-01

    Taste bud type II cells fire action potentials in response to tastants, triggering nonvesicular ATP release to gustatory neurons via voltage-gated CALHM1-associated ion channels. Whereas CALHM1 regulates mouse cortical neuron excitability, its roles in regulating type II cell excitability are unknown. In this study, we compared membrane conductances and action potentials in single identified TRPM5-GFP-expressing circumvallate papillae type II cells acutely isolated from wild-type (WT) and Calhm1 knockout (KO) mice. The activation kinetics of large voltage-gated outward currents were accelerated in cells from Calhm1 KO mice, and their associated nonselective tail currents, previously shown to be highly correlated with ATP release, were completely absent in Calhm1 KO cells, suggesting that CALHM1 contributes to all of these currents. Calhm1 deletion did not significantly alter resting membrane potential or input resistance, the amplitudes and kinetics of Na+ currents either estimated from action potentials or recorded from steady-state voltage pulses, or action potential threshold, overshoot peak, afterhyperpolarization, and firing frequency. However, Calhm1 deletion reduced the half-widths of action potentials and accelerated the deactivation kinetics of transient outward currents, suggesting that the CALHM1-associated conductance becomes activated during the repolarization phase of action potentials. NEW & NOTEWORTHY CALHM1 is an essential ion channel component of the ATP neurotransmitter release mechanism in type II taste bud cells. Its contribution to type II cell resting membrane properties and excitability is unknown. Nonselective voltage-gated currents, previously associated with ATP release, were absent in cells lacking CALHM1. Calhm1 deletion was without effects on resting membrane properties or voltage-gated Na+ and K+ channels but contributed modestly to the kinetics of action potentials. PMID:28202574

  12. A New Class III Antiarrhythmic Drug Niferidil Prolongs Action Potentials in Guinea Pig Atrial Myocardium via Inhibition of Rapid Delayed Rectifier.

    Science.gov (United States)

    Abramochkin, Denis V; Kuzmin, Vladislav S; Rosenshtraukh, Leonid V

    2017-12-01

    A new class III antiarrhythmic drug niferidil (RG-2) has been introduced as a highly effective therapy for cases of persistent atrial fibrillation, but ionic mechanisms of its action are poorly understood. In the present study, the effects of niferidil on action potential (AP) waveform and potassium currents responsible for AP repolarization were investigated in guinea pig atrial myocardium. APs were recorded with sharp glass microelectrodes in multicellular atrial preparations. Whole-cell patch-clamp technique was used to measure K + currents in isolated myocytes. In multicellular atrial preparations, 10 -8  M niferidil effectively prolonged APs by 15.2 ± 2.8% at 90% repolarization level. However, even the highest tested concentrations, 10 -6  M and 10 -5  M failed to prolong APs more than 32.5% of control duration. The estimated concentration of niferedil for half-maximal AP prolongation was 1.13 × 10 -8  M. Among the potassium currents responsible for AP repolarization phase, I K1 was found to be almost insensitive to niferidil. However, another inward rectifier, I KACh , was effectively suppressed by micromolar concentrations of niferidil with IC 50  = 9.2 × 10 -6  M. I KATP was much less sensitive to the drug with IC 50  = 2.26 × 10 -4  M. The slow component of delayed rectifier, I Ks , also demonstrated low sensitivity to niferidil-the highest used concentration, 10 -4  M, decreased peak I Ks density to 46.2 ± 5.5% of control. Unlike I Ks , the rapid component of delayed rectifier, I Kr , appeared to be extremely sensitive to niferidil. The IC 50 was 1.26 × 10 -9  M. I Kr measured in ventricular myocytes was found to be less sensitive to niferidil with IC 50  = 3.82 × 10 -8  M. Niferidil prolongs APs in guinea pig atrial myocardium via inhibition of I Kr .

  13. Glucoregulation after canine islet transplantation : Contribution of insulin secretory capacity, insulin action, and the entero-insular axis

    NARCIS (Netherlands)

    vanderBurg, MPM; van Suylichem, PTR; Guicherit, OR; Frolich, M; Lemkes, HHPJ; Gooszen, HG

    1997-01-01

    The physiological glucoregulatory mechanisms after islet transplantation have been incompletely investigated, We studied the insulin secretory capacity (ISC) by intravenous arginine stimulation during 35-mM glucose clamps, insulin action during hyperinsulinemic euglycemic clamps, and mixed-meal

  14. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    2015-12-01

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

  17. Action without Action Planning: The Potential of the Career Thinking Session in Enabling Transformational Career Learning and Development

    Science.gov (United States)

    Bassot, Barbara

    2017-01-01

    This paper examines the potential of the Career Thinking Session (CTS) model to career guidance and counselling practice with young people. A qualitative research study is presented, focusing on the case study of a client involved in the transition to higher education. The setting for the research is described and the origins of the CTS are…

  18. Cell-Detection Technique for Automated Patch Clamping

    Science.gov (United States)

    McDowell, Mark; Gray, Elizabeth

    2008-01-01

    A unique and customizable machinevision and image-data-processing technique has been developed for use in automated identification of cells that are optimal for patch clamping. [Patch clamping (in which patch electrodes are pressed against cell membranes) is an electrophysiological technique widely applied for the study of ion channels, and of membrane proteins that regulate the flow of ions across the membranes. Patch clamping is used in many biological research fields such as neurobiology, pharmacology, and molecular biology.] While there exist several hardware techniques for automated patch clamping of cells, very few of those techniques incorporate machine vision for locating cells that are ideal subjects for patch clamping. In contrast, the present technique is embodied in a machine-vision algorithm that, in practical application, enables the user to identify good and bad cells for patch clamping in an image captured by a charge-coupled-device (CCD) camera attached to a microscope, within a processing time of one second. Hence, the present technique can save time, thereby increasing efficiency and reducing cost. The present technique involves the utilization of cell-feature metrics to accurately make decisions on the degree to which individual cells are "good" or "bad" candidates for patch clamping. These metrics include position coordinates (x,y) in the image plane, major-axis length, minor-axis length, area, elongation, roundness, smoothness, angle of orientation, and degree of inclusion in the field of view. The present technique does not require any special hardware beyond commercially available, off-the-shelf patch-clamping hardware: A standard patchclamping microscope system with an attached CCD camera, a personal computer with an imagedata- processing board, and some experience in utilizing imagedata- processing software are all that are needed. A cell image is first captured by the microscope CCD camera and image-data-processing board, then the image

  19. Melatonin: Action as antioxidant and potential applications in human disease and aging

    International Nuclear Information System (INIS)

    Bonnefont-Rousselot, Dominique; Collin, Fabrice

    2010-01-01

    This review aims at describing the beneficial properties of melatonin related to its antioxidant effects. Oxidative stress, i.e., an imbalance between the production of reactive oxygen species and antioxidant defences, is involved in several pathological conditions such as cardiovascular or neurological disease, and in aging. Therefore, research for antioxidants has developed. However, classical antioxidants often failed to exhibit beneficial effects, especially in metabolic diseases. Melatonin has been shown as a specific antioxidant due to its amphiphilic feature that allows it to cross physiological barriers, thereby reducing oxidative damage in both lipid and aqueous cell environments. Studies on the antioxidant action of melatonin are reported, with a special mention to water gamma radiolysis as a method to produce oxygen-derived free radicals, and on structure-activity relationships of melatonin derivatives. Mass spectrometry-based techniques have been developed to identify melatonin oxidation products. Besides its ability to scavenge several radical species, melatonin regulates the activity of antioxidant enzymes (indirect antioxidant properties). Efficient detection methods confirmed the presence of melatonin in several plant products. Therapeutic potential of melatonin relies either on increasing melatonin dietary intake or on supplementation with supraphysiological dosages. Clinical trials showed that melatonin could be efficient in preventing cell damage, as well under acute (sepsis, asphyxia in newborns) as under chronic (metabolic and neurodegenerative diseases, cancer, inflammation, aging). Its global action on oxidative stress, together with its rhythmicity that plays a role in several metabolic functions, lead melatonin to be of great interest for future clinical research in order to improve public health.

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  1. Ventricular action potential adaptation to regular exercise: role of β-adrenergic and KATP channel function.

    Science.gov (United States)

    Wang, Xinrui; Fitts, Robert H

    2017-08-01

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

  2. Load-deflection characteristics of small bore insulated pipe clamps

    International Nuclear Information System (INIS)

    Severud, L.K.; Clark, G.L.

    1982-01-01

    High temperature LMFBR piping is subject to rapid temperature changes during transient events. Typically, this pipe is supported by specially designed insulated pipe clamps to prevent excessive thermal stress from developing during these transients. The special insulated clamps used on both FFTF and CRBR piping utilize a Belleville spring arrangement to compensate for pipe thermal expansion. Analysis indicates that this produces a non-linear, directionally sensitive clamp spring rate. Since these spring rates influence the seismic response of a supported piping system, it was deemed necessary to evaluate them further by test. This has been accomplished for the FFTF clamps. A more standard insulated pipe clamp, which does not incorporate Belleville springs to accommodate thermal expansion, was also tested. This type clamp is simple in design, and economically attractive. It may have wide application prospects for use in LMFBR small bore auxiliary piping operating at temperatures below 427 0 C. Load deflection tests were conducted on 2.54 CM and 7.62 CM diameter samples of these commercial clamps

  3. Design and control of a novel gastroscope intervention mechanism with circumferentially pneumatic-driven clamping function.

    Science.gov (United States)

    Li, Yanmin; Liu, Hao; Hao, Siwen; Li, Hongyi; Han, Jianda; Yang, Yunsheng

    2017-03-01

    Robot-assisted manipulation is promising for solving problems such as understaffing and the risk of infection in gastro-intestinal endoscopy. However, the commonly used friction rollers in few existing systems have a potential risk of deforming flexible endoscopes for non-uniform clamping. This paper presents a robotic system for a standard flexible endoscope and focuses on a novel gastroscope intervention mechanism (GIM), which provides circumferentially uniform clamping with an airbag. The GIM works with a relay-on mechanism in a way similar to manual operation. The shear stiffness of airbag and the critical slipping force (CSF) were analysed to determine the parameters of the airbag. A fuzzy PID controller was employed to realize a fast response and high accuracy of pneumatic actuation. Experiments were performed to evaluate the accuracy, stiffness and CSF. In vitro and in vivo animal experiments were also carried out. The GIM realized an accuracy of 0.025 ± 0.2 mm and -0.03 ± 0.25° for push-pull and rotation without delivery resistance. Under polynomial could be used to describe the relationship between the CSF and pneumatic pressure. The novel GIM could effectively deliver gastroscopes. The pneumatic-driven clamping method proposed could protect the gastroscope by circumferentially uniform clamping force and the CSF could be properly controlled to guarantee operating safety. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  4. In vivo patch-clamp analysis of response properties of rat primary somatosensory cortical neurons responding to noxious stimulation of the facial skin

    Directory of Open Access Journals (Sweden)

    Nasu Masanori

    2010-05-01

    Full Text Available Abstract Background Although it has been widely accepted that the primary somatosensory (SI cortex plays an important role in pain perception, it still remains unclear how the nociceptive mechanisms of synaptic transmission occur at the single neuron level. The aim of the present study was to examine whether noxious stimulation applied to the orofacial area evokes the synaptic response of SI neurons in urethane-anesthetized rats using an in vivo patch-clamp technique. Results In vivo whole-cell current-clamp recordings were performed in rat SI neurons (layers III-IV. Twenty-seven out of 63 neurons were identified in the mechanical receptive field of the orofacial area (36 neurons showed no receptive field and they were classified as non-nociceptive (low-threshold mechanoreceptive; 6/27, 22% and nociceptive neurons. Nociceptive neurons were further divided into wide-dynamic range neurons (3/27, 11% and nociceptive-specific neurons (18/27, 67%. In the majority of these neurons, a proportion of the excitatory postsynaptic potentials (EPSPs reached the threshold, and then generated random discharges of action potentials. Noxious mechanical stimuli applied to the receptive field elicited a discharge of action potentials on the barrage of EPSPs. In the case of noxious chemical stimulation applied as mustard oil to the orofacial area, the membrane potential shifted depolarization and the rate of spontaneous discharges gradually increased as did the noxious pinch-evoked discharge rates, which were usually associated with potentiated EPSP amplitudes. Conclusions The present study provides evidence that SI neurons in deep layers III-V respond to the temporal summation of EPSPs due to noxious mechanical and chemical stimulation applied to the orofacial area and that these neurons may contribute to the processing of nociceptive information, including hyperalgesia.

  5. Is "Delayed Umbilical Cord Clamping" Beneficial for Premature Newborns?

    Directory of Open Access Journals (Sweden)

    Amir-Mohammad Armanian

    2017-05-01

    Full Text Available Background: The appropriate moment for clamping the umbilical cord is controversial. Immediate cord clamping (ICC is an item of active management of the third stage of labor (AMTSL. Unclamped umbilical cord may cause inconvenience in preterm neonates because they commonly need some levels of emergent services. Some studies revealed delayed cord clamping (DCC of preterm neonates results in better health conditions like lower rates of respiratory distress syndrome (RDS, less morbidities in labor room and lower risk of postpartum hemorrhage. The aim of the present study was to determine the effect of delayed umbilical cord clamping on premature neonatal outcomes. Materials and Methods: In this single‑center randomized control trial study, sixty premature neonates (gestational age ≤ 34 weeks were randomly assigned to ICC (cord clamped at 5–10 seconds or DCC (30–45 seconds groups and followed up in neonatal intensive care unit (NICU. Primary outcomes were 1st and 5th minute Apgar score, average of level of hematocrit after birth, intra ventricle hemorrhage and need some levels of resuscitation. Results: Differences in demographic characteristics were not statistically significant. After birth, neonates who had delayed clamping had significantly higher mean hematocrit after at 4-hour of birth (49.58+5.15gr/dl vs. 46.58+5.40gr/dlin DCC vs. ICC groups, respectively (P=0.031. Delayed cord clamping reduced the duration of need to nasal continues positive airway pressure (NCPAP (86.7% and 60.0% in ICC and DCC groups, respectively, P= 0.039. Attractively, the results showed lower incidence of clinical sepsis in delayed cord clamping neonates (53.3% vs. 23.3% in ICC and DCC groups, respectively, P=0.033. Conclusion: Prematurity complications might decrease by delay umbilical cord clamping which improve the hematocrit, duration of need to NCPAP and incidence of clinical sepsis. Furthermore, DCC may have no negative impact on neonatal resuscitation.

  6. Frequency decoding of periodically timed action potentials through distinct activity patterns in a random neural network

    International Nuclear Information System (INIS)

    Reichenbach, Tobias; Hudspeth, A J

    2012-01-01

    Frequency discrimination is a fundamental task of the auditory system. The mammalian inner ear, or cochlea, provides a place code in which different frequencies are detected at different spatial locations. However, a temporal code based on spike timing is also available: action potentials evoked in an auditory-nerve fiber by a low-frequency tone occur at a preferred phase of the stimulus—they exhibit phase locking—and thus provide temporal information about the tone's frequency. Humans employ this temporal information for discrimination of low frequencies. How might such temporal information be read out in the brain? Here we employ statistical and numerical methods to demonstrate that recurrent random neural networks in which connections between neurons introduce characteristic time delays, and in which neurons require temporally coinciding inputs for spike initiation, can perform sharp frequency discrimination when stimulated with phase-locked inputs. Although the frequency resolution achieved by such networks is limited by the noise in phase locking, the resolution for realistic values reaches the tiny frequency difference of 0.2% that has been measured in humans. (paper)

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

    Science.gov (United States)

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

    2015-01-01

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

  8. 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.

  9. A novel framework for feature extraction in multi-sensor action potential sorting.

    Science.gov (United States)

    Wu, Shun-Chi; Swindlehurst, A Lee; Nenadic, Zoran

    2015-09-30

    Extracellular recordings of multi-unit neural activity have become indispensable in neuroscience research. The analysis of the recordings begins with the detection of the action potentials (APs), followed by a classification step where each AP is associated with a given neural source. A feature extraction step is required prior to classification in order to reduce the dimensionality of the data and the impact of noise, allowing source clustering algorithms to work more efficiently. In this paper, we propose a novel framework for multi-sensor AP feature extraction based on the so-called Matched Subspace Detector (MSD), which is shown to be a natural generalization of standard single-sensor algorithms. Clustering using both simulated data and real AP recordings taken in the locust antennal lobe demonstrates that the proposed approach yields features that are discriminatory and lead to promising results. Unlike existing methods, the proposed algorithm finds joint spatio-temporal feature vectors that match the dominant subspace observed in the two-dimensional data without needs for a forward propagation model and AP templates. The proposed MSD approach provides more discriminatory features for unsupervised AP sorting applications. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Yoona Kim

    2017-11-01

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

  11. Boron-doped nanocrystalline diamond microelectrode arrays monitor cardiac action potentials.

    Science.gov (United States)

    Maybeck, Vanessa; Edgington, Robert; Bongrain, Alexandre; Welch, Joseph O; Scorsone, Emanuel; Bergonzo, Philippe; Jackman, Richard B; Offenhäusser, Andreas

    2014-02-01

    The expansion of diamond-based electronics in the area of biological interfacing has not been as thoroughly explored as applications in electrochemical sensing. However, the biocompatibility of diamond, large safe electrochemical window, stability, and tunable electronic properties provide opportunities to develop new devices for interfacing with electrogenic cells. Here, the fabrication of microelectrode arrays (MEAs) with boron-doped nanocrystalline diamond (BNCD) electrodes and their interfacing with cardiomyocyte-like HL-1 cells to detect cardiac action potentials are presented. A nonreductive means of structuring doped and undoped diamond on the same substrate is shown. The resulting BNCD electrodes show high stability under mechanical stress generated by the cells. It is shown that by fabricating the entire surface of the MEA with NCD, in patterns of conductive doped, and isolating undoped regions, signal detection may be improved up to four-fold over BNCD electrodes passivated with traditional isolators. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    Directory of Open Access Journals (Sweden)

    Domenico F Galati

    2016-09-01

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

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

    Science.gov (United States)

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

    2015-02-03

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

  14. Action Potential Energy Efficiency Varies Among Neuron Types in Vertebrates and Invertebrates

    Science.gov (United States)

    Sengupta, Biswa; Stemmler, Martin; Laughlin, Simon B.; Niven, Jeremy E.

    2010-01-01

    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. PMID:20617202

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

    Directory of Open Access Journals (Sweden)

    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.

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    M.R. Moreira

    2001-10-01

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

  18. Variations in interpulse interval of double action potentials during propagation in single neurons.

    Science.gov (United States)

    Villagran-Vargas, Edgar; Rodríguez-Sosa, Leonardo; Hustert, Reinhold; Blicher, Andreas; Laub, Katrine; Heimburg, Thomas

    2013-02-01

    In this work, we analyzed the interpulse interval (IPI) of doublets and triplets in single neurons of three biological models. Pulse trains with two or three spikes originate from the process of sensory mechanotransduction in neurons of the locust femoral nerve, as well as through spontaneous activity both in the abdominal motor neurons and the caudal photoreceptor of the crayfish. We show that the IPI for successive low-frequency single action potentials, as recorded with two electrodes at two different points along a nerve axon, remains constant. On the other hand, IPI in doublets either remains constant, increases or decreases by up to about 3 ms as the pair propagates. When IPI increases, the succeeding pulse travels at a slower speed than the preceding one. When IPI is reduced, the succeeding pulse travels faster than the preceding one and may exceed the normal value for the specific neuron. In both cases, IPI increase and reduction, the speed of the preceding pulse differs slightly from the normal value, therefore the two pulses travel at different speeds in the same nerve axon. On the basis of our results, we may state that the effect of attraction or repulsion in doublets suggests a tendency of the spikes to reach a stable configuration. We strongly suggest that the change in IPI during spike propagation of doublets opens up a whole new realm of possibilities for neural coding and may have major implications for understanding information processing in nervous systems. Copyright © 2012 Wiley Periodicals, Inc.

  19. 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.

  20. 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.

  1. Action Potential Shortening and Impairment of Cardiac Function by Ablation of Slc26a6.

    Science.gov (United States)

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

    2017-10-01

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

  2. 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 ...

  3. 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

  4. Associations between motor unit action potential parameters and surface EMG features.

    Science.gov (United States)

    Del Vecchio, Alessandro; Negro, Francesco; Felici, Francesco; Farina, Dario

    2017-10-01

    The surface interference EMG signal provides some information on the neural drive to muscles. However, the association between neural drive to muscle and muscle activation has long been debated with controversial indications due to the unavailability of motor unit population data. In this study, we clarify the potential and limitations of interference EMG analysis to infer motor unit recruitment strategies with an experimental investigation of several concurrently active motor units and of the associated features of the surface EMG. For this purpose, we recorded high-density surface EMG signals during linearly increasing force contractions of the tibialis anterior muscle, up to 70% of maximal force. The recruitment threshold (RT), conduction velocity (MUCV), median frequency (MDF MU ), and amplitude (RMS MU ) of action potentials of 587 motor units from 13 individuals were assessed and associated with features of the interference EMG. MUCV was positively associated with RT ( R 2 = 0.64 ± 0.14), whereas MDF MU and RMS MU showed a weaker relation with RT ( R 2 = 0.11 ± 0.11 and 0.39 ± 0.24, respectively). Moreover, the changes in average conduction velocity estimated from the interference EMG predicted well the changes in MUCV ( R 2 = 0.71), with a strong association to ankle dorsiflexion force ( R 2 = 0.81 ± 0.12). Conversely, both the average EMG MDF and RMS were poorly associated with motor unit recruitment. These results clarify the limitations of EMG spectral and amplitude analysis in inferring the neural strategies of muscle control and indicate that, conversely, the average conduction velocity could provide relevant information on these strategies. NEW & NOTEWORTHY The surface EMG provides information on the neural drive to muscles. However, the associations between EMG features and neural drive have been long debated due to unavailability of motor unit population data. Here, by using novel highly accurate decomposition of the EMG, we related motor unit

  5. Motor Unit Action Potential Clustering—Theoretical Consideration for Muscle Activation during a Motor Task

    Directory of Open Access Journals (Sweden)

    Michael J. Asmussen

    2018-01-01

    Full Text Available During dynamic or sustained isometric contractions, bursts of muscle activity appear in the electromyography (EMG signal. Theoretically, these bursts of activity likely occur because motor units are constrained to fire temporally close to one another and thus the impulses are “clustered” with short delays to elicit bursts of muscle activity. The purpose of this study was to investigate whether a sequence comprised of “clustered” motor unit action potentials (MUAP can explain spectral and amplitude changes of the EMG during a simulated motor task. This question would be difficult to answer experimentally and thus, required a model to study this type of muscle activation pattern. To this end, we modeled two EMG signals, whereby a single MUAP was either convolved with a randomly distributed impulse train (EMG-rand or a “clustered” sequence of impulses (EMG-clust. The clustering occurred in windows lasting 5–100 ms. A final mixed signal of EMG-clust and EMG-rand, with ratios (1:1–1:10, was also modeled. A ratio of 1:1 would indicate that 50% of MUAP were randomly distributed, while 50% of “clustered” MUAP occurred in a given time window (5–100 ms. The results of the model showed that clustering MUAP caused a downshift in the mean power frequency (i.e., ~30 Hz with the largest shift occurring with a cluster window of 10 ms. The mean frequency shift was largest when the ratio of EMG-clust to EMG-rand was high. Further, the clustering of MUAP also caused a substantial increase in the amplitude of the EMG signal. This model potentially explains an activation pattern that changes the EMG spectra during a motor task and thus, a potential activation pattern of muscles observed experimentally. Changes in EMG measurements during fatiguing conditions are typically attributed to slowing of conduction velocity but could, per this model, also result from changes of the clustering of MUAP. From a clinical standpoint, this type of muscle

  6. Facilitating Youth to Take Sustainability Actions: The Potential of Peer Education

    Science.gov (United States)

    de Vreede, Catherine; Warner, Alan; Pitter, Robert

    2014-01-01

    Peer education is an understudied yet valuable strategy for sustainability educators in shifting youth to take action for sustainability. This case study conceptualizes the change process in facilitating youth to take sustainability actions, and explores the benefits, dynamics, and challenges of peer education as a strategy in facilitating change.…

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

    Science.gov (United States)

    Witt, Jessica K

    2017-08-01

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

  8. Lotus birth, a holistic approach on physiological cord clamping.

    Science.gov (United States)

    Zinsser, Laura A

    2018-04-01

    The positive effects of delayed cord clamping (DCC) has been extensively researched. DCC means: waiting at least one minute after birth before clamping and cutting the cord or till the pulsation has stopped. With physiological clamping and cutting (PCC) the clamping and cutting can happen at the earliest after the pulsation has stopped. With a Lotus birth, no clamping and cutting of the cord is done. A woman called Clair Lotus Day imitated the holistic approach of PCC from an anthropoid ape in 1974. The chimpanzee did not separate the placenta from the newborn. The aim of this case report is to discuss and learn a different approach in the third stage of labour. Three cases of Lotus birth by human beings were observed. All three women gave birth in an out-of-hospital setting and had ambulant postnatal care. The placenta was washed, salted and herbs were put on 2-3h post partum. The placenta was wrapped in something that absorbs the moisture. The salting was repeated with a degreasing frequency depending on moistness of the placenta. On life day six all three Lotus babies experiences a natural separation of the cord. All three Lotus birth cases were unproblematic, no special incidence occurred. One should differentiate between early cord clamping (ECC), delayed cord clamping (DCC) and physiological cord clamping (PCC). Lotus birth might lead to an optimisation of the bonding and attachment. Research is needed in the areas of both PCC and Lotus birth. Copyright © 2017 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2018-01-01

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

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

    Science.gov (United States)

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

    2016-06-01

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

  11. Dynamics of action potential backpropagation in basal dendrites of prefrontal cortical pyramidal neurons.

    Science.gov (United States)

    Zhou, Wen-Liang; Yan, Ping; Wuskell, Joseph P; Loew, Leslie M; Antic, Srdjan D

    2008-02-01

    Basal dendrites of neocortical pyramidal neurons are relatively short and directly attached to the cell body. This allows electrical signals arising in basal dendrites to strongly influence the neuronal output. Likewise, somatic action potentials (APs) should readily propagate back into the basilar dendritic tree to influence synaptic plasticity. Two recent studies, however, determined that sodium APs are severely attenuated in basal dendrites of cortical pyramidal cells, so that they completely fail in distal dendritic segments. Here we used the latest improvements in the voltage-sensitive dye imaging technique (Zhou et al., 2007) to study AP backpropagation in basal dendrites of layer 5 pyramidal neurons of the rat prefrontal cortex. With a signal-to-noise ratio of > 15 and minimal temporal averaging (only four sweeps) we were able to sample AP waveforms from the very last segments of individual dendritic branches (dendritic tips). We found that in short- (< 150 microm) and medium (150-200 microm in length)-range basal dendrites APs backpropagated with modest changes in AP half-width or AP rise-time. The lack of substantial changes in AP shape and dynamics of rise is inconsistent with the AP-failure model. The lack of substantial amplitude boosting of the third AP in the high-frequency burst also suggests that in short- and medium-range basal dendrites backpropagating APs were not severely attenuated. Our results show that the AP-failure concept does not apply in all basal dendrites of the rat prefrontal cortex. The majority of synaptic contacts in the basilar dendritic tree actually received significant AP-associated electrical and calcium transients.

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

    Science.gov (United States)

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

    2015-01-15

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

  13. Impedance and electrically evoked compound action potential (ECAP drop within 24 hours after cochlear implantation.

    Directory of Open Access Journals (Sweden)

    Joshua Kuang-Chao Chen

    Full Text Available Previous animal study revealed that post-implantation electrical detection levels significantly declined within days. The impact of cochlear implant (CI insertion on human auditory pathway in terms of impedance and electrically evoked compound action potential (ECAP variation within hours after surgery remains unclear, since at this time frequency mapping can only commence weeks after implantation due to factors associated with wound conditions. The study presented our experiences with regards to initial switch-on within 24 hours, and thus the findings about the milieus inside cochlea within the first few hours after cochlear implantation in terms of impedance/ECAP fluctuations. The charts of fifty-four subjects with profound hearing impairment were studied. A minimal invasive approach was used for cochlear implantation, characterized by a small skin incision (≈ 2.5 cm and soft techniques for cochleostomy. Impedance/ECAP was measured intro-operatively and within 24 hours post-operatively. Initial mapping within 24 hours post-operatively was performed in all patients without major complications. Impedance/ECAP became significantly lower measured within 24 hours post-operatively as compared with intra-operatively (p<0.001. There were no differences between pre-operative and post-operative threshold for air-conduction hearing. A significant drop of impedance/ECAP in one day after cochlear implantation was revealed for the first time in human beings. Mechanisms could be related to the restoration of neuronal sensitivity to the electrical stimulation, and/or the interaction between the matrix enveloping the electrodes and the electrical stimulation of the initial switch-on. Less wound pain/swelling and soft techniques both contributed to the success of immediate initial mapping, which implied a stable micro-environment inside the cochlea despite electrodes insertion. Our research invites further studies to correlate initial impedance/ECAP changes

  14. Recording single neurons' action potentials from freely moving pigeons across three stages of learning.

    Science.gov (United States)

    Starosta, Sarah; Stüttgen, Maik C; Güntürkün, Onur

    2014-06-02

    While the subject of learning has attracted immense interest from both behavioral and neural scientists, only relatively few investigators have observed single-neuron activity while animals are acquiring an operantly conditioned response, or when that response is extinguished. But even in these cases, observation periods usually encompass only a single stage of learning, i.e. acquisition or extinction, but not both (exceptions include protocols employing reversal learning; see Bingman et al.(1) for an example). However, acquisition and extinction entail different learning mechanisms and are therefore expected to be accompanied by different types and/or loci of neural plasticity. Accordingly, we developed a behavioral paradigm which institutes three stages of learning in a single behavioral session and which is well suited for the simultaneous recording of single neurons' action potentials. Animals are trained on a single-interval forced choice task which requires mapping each of two possible choice responses to the presentation of different novel visual stimuli (acquisition). After having reached a predefined performance criterion, one of the two choice responses is no longer reinforced (extinction). Following a certain decrement in performance level, correct responses are reinforced again (reacquisition). By using a new set of stimuli in every session, animals can undergo the acquisition-extinction-reacquisition process repeatedly. Because all three stages of learning occur in a single behavioral session, the paradigm is ideal for the simultaneous observation of the spiking output of multiple single neurons. We use pigeons as model systems, but the task can easily be adapted to any other species capable of conditioned discrimination learning.

  15. 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.

  16. 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.

  17. Inter-subject variability in human atrial action potential in sinus rhythm versus chronic atrial fibrillation.

    Directory of Open Access Journals (Sweden)

    Carlos Sánchez

    Full Text Available Human atrial electrophysiology exhibits high inter-subject variability in both sinus rhythm (SR and chronic atrial fibrillation (cAF patients. Variability is however rarely investigated in experimental and theoretical electrophysiological studies, thus hampering the understanding of its underlying causes but also its implications in explaining differences in the response to disease and treatment. In our study, we aim at investigating the ability of populations of human atrial cell models to capture the inter-subject variability in action potential (AP recorded in 363 patients both under SR and cAF conditions.Human AP recordings in atrial trabeculae (n = 469 from SR and cAF patients were used to calibrate populations of computational SR and cAF atrial AP models. Three populations of over 2000 sampled models were generated, based on three different human atrial AP models. Experimental calibration selected populations of AP models yielding AP with morphology and duration in range with experimental recordings. Populations using the three original models can mimic variability in experimental AP in both SR and cAF, with median conductance values in SR for most ionic currents deviating less than 30% from their original peak values. All cAF populations show similar variations in G(K1, G(Kur and G(to, consistent with AF-related remodeling as reported in experiments. In all SR and cAF model populations, inter-subject variability in I(K1 and I(NaK underlies variability in APD90, variability in I(Kur, I(CaL and I(NaK modulates variability in APD50 and combined variability in Ito and I(Kur determines variability in APD20. The large variability in human atrial AP triangulation is mostly determined by I(K1 and either I(NaK or I(NaCa depending on the model.Experimentally-calibrated human atrial AP models populations mimic AP variability in SR and cAF patient recordings, and identify potential ionic determinants of inter-subject variability in human atrial AP

  18. Synthesis of sulfenamides, derivatives of morpholine, 4-aminomorpholine and thiomorpholine as compounds of potential radioprotective action

    Energy Technology Data Exchange (ETDEWEB)

    Strzelczyk, M.; Kucharski, A. (Wojskowa Akademia Medyczna, Lodz (Poland))

    1979-01-01

    Sulfenamides belong to the group of compounds displaying radioprotective action. Their mechanism of action is based mainly on the protection against oxygenation. Six compounds were synthetized four of which i.e. 3-nitrophenylothiomorpholine, 2,4-dinitrophenylothiomorpholine, 2,4-dinitrophenylothio-4-aminomorpholine and 2,4-dinitrophenylothiothiomorpholine were to date not described in the literature. The structure of the synthetized compounds was confirmed by elementary and infrared spectral analysis.

  19. Ventilation onset prior to umbilical cord clamping (physiological-based cord clamping improves systemic and cerebral oxygenation in preterm lambs.

    Directory of Open Access Journals (Sweden)

    Graeme R Polglase

    Full Text Available As measurement of arterial oxygen saturation (SpO2 is common in the delivery room, target SpO2 ranges allow clinicians to titrate oxygen therapy for preterm infants in order to achieve saturation levels similar to those seen in normal term infants in the first minutes of life. However, the influence of the onset of ventilation and the timing of cord clamping on systemic and cerebral oxygenation is not known.We investigated whether the initiation of ventilation, prior to, or after umbilical cord clamping, altered systemic and cerebral oxygenation in preterm lambs.Systemic and cerebral blood-flows, pressures and peripheral SpO2 and regional cerebral tissue oxygenation (SctO2 were measured continuously in apnoeic preterm lambs (126±1 day gestation. Positive pressure ventilation was initiated either 1 prior to umbilical cord clamping, or 2 after umbilical cord clamping. Lambs were monitored intensively prior to intervention, and for 10 minutes following umbilical cord clamping.Clamping the umbilical cord prior to ventilation resulted in a rapid decrease in SpO2 and SctO2, and an increase in arterial pressure, cerebral blood flow and cerebral oxygen extraction. Ventilation restored oxygenation and haemodynamics by 5-6 minutes. No such disturbances in peripheral or cerebral oxygenation and haemodynamics were observed when ventilation was initiated prior to cord clamping.The establishment of ventilation prior to umbilical cord clamping facilitated a smooth transition to systemic and cerebral oxygenation following birth. SpO2 nomograms may need to be re-evaluated to reflect physiological management of preterm infants in the delivery room.

  20. Acute effects of ethanol on action potential and intracellular Ca2+ transient in cardiac ventricular cells: a simulation study

    Czech Academy of Sciences Publication Activity Database

    Pásek, Michal; Bébarová, M.; Christé, G.; Šimurdová, M.; Šimurda, J.

    2016-01-01

    Roč. 54, č. 5 (2016), s. 753-762 ISSN 0140-0118 Institutional support: RVO:61388998 Keywords : ethanol * cardiomyocyte * action potential * rat ventricular cell model * human ventricular cell model Subject RIV: BO - Biophysics Impact factor: 1.916, year: 2016

  1. 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 ...

  2. Analysis of electrically evoked compound action potential of the auditory nerve in children with bilateral cochlear implants.

    Science.gov (United States)

    Caldas, Fernanda Ferreira; Cardoso, Carolina Costa; Barreto, Monique Antunes de Souza Chelminski; Teixeira, Marina Santos; Hilgenberg, Anacléia Melo da Silva; Serra, Lucieny Silva Martins; Bahmad Junior, Fayez

    2016-01-01

    The cochlear implant device has the capacity to measure the electrically evoked compound action potential of the auditory nerve. The neural response telemetry is used in order to measure the electrically evoked compound action potential of the auditory nerve. To analyze the electrically evoked compound action potential, through the neural response telemetry, in children with bilateral cochlear implants. This is an analytical, prospective, longitudinal, historical cohort study. Six children, aged 1-4 years, with bilateral cochlear implant were assessed at five different intervals during their first year of cochlear implant use. There were significant differences in follow-up time (p=0.0082) and electrode position (p=0.0019) in the T-NRT measure. There was a significant difference in the interaction between time of follow-up and electrode position (p=0.0143) when measuring the N1-P1 wave amplitude between the three electrodes at each time of follow-up. The electrically evoked compound action potential measurement using neural response telemetry in children with bilateral cochlear implants during the first year of follow-up was effective in demonstrating the synchronized bilateral development of the peripheral auditory pathways in the studied population. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  3. Nanoelectronics-biology frontier: From nanoscopic probes for action potential recording in live cells to three-dimensional cyborg tissues

    OpenAIRE

    Duan, Xiaojie; Fu, Tian-Ming; Liu, Jia; Lieber, Charles M.

    2013-01-01

    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 signa...

  4. Meju, unsalted soybeans fermented with Bacillus subtilis and Aspergilus oryzae, potentiates insulinotropic actions and improves hepatic insulin sensitivity in diabetic rats

    Directory of Open Access Journals (Sweden)

    Yang Hye

    2012-05-01

    Full Text Available Abstract Background Although soybeans have the ability to attenuate insulin resistance, it is insufficient to alleviate type 2 diabetic symptoms and different types of fermented soybeans may have even better anti-diabetic effects. Meju, unsalted fermented soybeans exhibited better insulin sensitizing and insulinotropic actions than unfermented cooked soybeans (CSB. We investigated whether meju fermented in the traditional (TMS manner for 60 days and meju fermented in the standardized (MMS method inoculating Bacillus subtilis and Aspergillus oryzae for 6 days modulated insulin resistance, insulin secretion, and pancreatic β-cell growth and survival in 90% pancreatectomized (Px diabetic rats, a moderate and non-obese type 2 diabetic animal model. Methods Diabetic rats were divided into 3 groups: 1 TMS (n = 20, 2 MMS (n = 20 or 3 casein (control; n = 20. Rats were provided with a high fat diet (40 energy % fat containing assigned 10% meju for 8 weeks. At the end of experiment insulin resistance and insulin secretion capacity were measured by euglycemic hyperinsulinemic clamp and by hyperglycemic clamp, respectively. Additionally, β-cell mass and islet morphohometry were determined by immunohistochemistry and insulin signaling in the liver was measured by western blot. Results TMS and MMS increased isoflavonoid aglycones much more than CSB. CSB and TMS/MMS improved glucose tolerance in diabetic rats but the mechanism was different between treatments (P Conclusions The anti-diabetic action of MMS, especially when fermented with Bacillus subtilis and Aspergillus oryzae, was superior to CSB by increasing isoflavonoid aglycones and small peptides with regard to type 2 diabetic rats.

  5. Governance issues, potentials and failures of participative collective action in the Kafue Flats, Zambia

    Directory of Open Access Journals (Sweden)

    Harry Nixon Chabwela

    2010-09-01

    2004 for creating by-laws based on initiatives of local staff of the Department of Fisheries, local interest groups and researchers. A broad local debate on how to manage the fisheries in a sustainable way and develop locally based by-laws for joint management of fisheries gives good potential for success and appears promising for the future of fisheries in Kafue Flats. Despite many difficulties it is an example of local collective action in order to scale up governance of common-pool resources.

  6. A new clamp method for firing bricks | Obeng | Journal of Applied ...

    African Journals Online (AJOL)

    A new clamp method for firing bricks. ... Journal of Applied Science and Technology ... To overcome this operational deficiencies, a new method of firing bricks that uses brick clamp technique that incorporates a clamp wall of 60 cm thickness, a six tier approach of sealing the top of the clamp (by combination of green bricks) ...

  7. Axially Modulated Clamped-Guided Arch Resonator for Memory and Logic Applications

    KAUST Repository

    Hafiz, Md Abdullah Al; Tella, Sherif Adekunle; Alcheikh, Nouha; Fariborzi, Hossein; Younis, Mohammad I.

    2017-01-01

    We experimentally demonstrate memory and logic devices based on an axially modulated clamped-guided arch resonator. The device are electrostatically actuated and capacitively sensed, while the resonance frequency modulation is achieved through an axial electrostatic force from the guided side of the clamped-guided arch microbeam. We present two case studies: first, a dynamic memory based on the nonlinear frequency response of the resonator, and second, a reprogrammable two-input logic gate based on the linear frequency modulation of the resonator. These devices show energy cost per memory/logic operation in pJ, are fully compatible with CMOS fabrication processes, have the potential for on-chip system integration, and operate at room temperature.

  8. Axially Modulated Clamped-Guided Arch Resonator for Memory and Logic Applications

    KAUST Repository

    Hafiz, Md Abdullah Al

    2017-11-03

    We experimentally demonstrate memory and logic devices based on an axially modulated clamped-guided arch resonator. The device are electrostatically actuated and capacitively sensed, while the resonance frequency modulation is achieved through an axial electrostatic force from the guided side of the clamped-guided arch microbeam. We present two case studies: first, a dynamic memory based on the nonlinear frequency response of the resonator, and second, a reprogrammable two-input logic gate based on the linear frequency modulation of the resonator. These devices show energy cost per memory/logic operation in pJ, are fully compatible with CMOS fabrication processes, have the potential for on-chip system integration, and operate at room temperature.

  9. An accurate online calibration system based on combined clamp-shape coil for high voltage electronic current transformers.

    Science.gov (United States)

    Li, Zhen-hua; Li, Hong-bin; Zhang, Zhi

    2013-07-01

    Electronic transformers are widely used in power systems because of their wide bandwidth and good transient performance. However, as an emerging technology, the failure rate of electronic transformers is higher than that of traditional transformers. As a result, the calibration period needs to be shortened. Traditional calibration methods require the power of transmission line be cut off, which results in complicated operation and power off loss. This paper proposes an online calibration system which can calibrate electronic current transformers without power off. In this work, the high accuracy standard current transformer and online operation method are the key techniques. Based on the clamp-shape iron-core coil and clamp-shape air-core coil, a combined clamp-shape coil is designed as the standard current transformer. By analyzing the output characteristics of the two coils, the combined clamp-shape coil can achieve verification of the accuracy. So the accuracy of the online calibration system can be guaranteed. Moreover, by employing the earth potential working method and using two insulating rods to connect the combined clamp-shape coil to the high voltage bus, the operation becomes simple and safe. Tests in China National Center for High Voltage Measurement and field experiments show that the proposed system has a high accuracy of up to 0.05 class.

  10. An accurate online calibration system based on combined clamp-shape coil for high voltage electronic current transformers

    International Nuclear Information System (INIS)

    Li, Zhen-hua; Li, Hong-bin; Zhang, Zhi

    2013-01-01

    Electronic transformers are widely used in power systems because of their wide bandwidth and good transient performance. However, as an emerging technology, the failure rate of electronic transformers is higher than that of traditional transformers. As a result, the calibration period needs to be shortened. Traditional calibration methods require the power of transmission line be cut off, which results in complicated operation and power off loss. This paper proposes an online calibration system which can calibrate electronic current transformers without power off. In this work, the high accuracy standard current transformer and online operation method are the key techniques. Based on the clamp-shape iron-core coil and clamp-shape air-core coil, a combined clamp-shape coil is designed as the standard current transformer. By analyzing the output characteristics of the two coils, the combined clamp-shape coil can achieve verification of the accuracy. So the accuracy of the online calibration system can be guaranteed. Moreover, by employing the earth potential working method and using two insulating rods to connect the combined clamp-shape coil to the high voltage bus, the operation becomes simple and safe. Tests in China National Center for High Voltage Measurement and field experiments show that the proposed system has a high accuracy of up to 0.05 class

  11. Applications of Dynamic Clamp to Cardiac Arrhythmia Research: Role in Drug Target Discovery and Safety Pharmacology Testing

    Directory of Open Access Journals (Sweden)

    Francis A. Ortega

    2018-01-01

    Full Text Available Dynamic clamp, a hybrid-computational-experimental technique that has been used to elucidate ionic mechanisms underlying cardiac electrophysiology, is emerging as a promising tool in the discovery of potential anti-arrhythmic targets and in pharmacological safety testing. Through the injection of computationally simulated conductances into isolated cardiomyocytes in a real-time continuous loop, dynamic clamp has greatly expanded the capabilities of patch clamp outside traditional static voltage and current protocols. Recent applications include fine manipulation of injected artificial conductances to identify promising drug targets in the prevention of arrhythmia and the direct testing of model-based hypotheses. Furthermore, dynamic clamp has been used to enhance existing experimental models by addressing their intrinsic limitations, which increased predictive power in identifying pro-arrhythmic pharmacological compounds. Here, we review the recent advances of the dynamic clamp technique in cardiac electrophysiology with a focus on its future role in the development of safety testing and discovery of anti-arrhythmic drugs.

  12. The Potential of General Classroom Observation: Turkish EFL Teachers' Perceptions, Sentiments, and Readiness for Action

    Science.gov (United States)

    Merç, Ali

    2015-01-01

    The purpose of this study was to determine Turkish EFL teachers' attitudes towards classroom observation. 204 teachers from different school settings responded to an online questionnaire. Data were analyzed according to three types of attitudes towards classroom observation: perceptions, sentiments, and readiness for action. The findings revealed…

  13. 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

  14. 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.

  15. Motivations and possible actions of potential criminal adversaries of US nuclear programs

    International Nuclear Information System (INIS)

    Bass, G.; Jenkins, B.; Kellen, K.; Krofcheek, J.; Petty, G.; Reinstedt, R.; Ronfeldt, D.

    1981-01-01

    The motivations that might impel individuals or groups to undertake criminal actions against US nuclear facilities or programs are explored in the report (R and R-2554-SL) from which this note is taken. The analysis involves examination of the motivations behind nuclear-related crimes that have already occurred and of those behind analogous nonnuclear crimes

  16. On the Potentials for Synergy Between COST Action TU1406 and the JCSS

    DEFF Research Database (Denmark)

    Nielsen, Michael Havbro Faber

    On of the main challenges of COST Action TU1406 is to identify, categorize and to the extent possible represent performance indicators of roadway bridges in a manner supporting decision making for their service life integrity management. This calls for an information consistent approach accounting...

  17. Preparing Social Justice Oriented Teachers: The Potential Role of Action Research in the PDS

    Science.gov (United States)

    Dodman, Stephanie L.; Lai, Kerri; Campet, Melissa; Cavallero-Lotocki, Renee; Hopkins, Aaron; Onidi, Christine

    2014-01-01

    Deliberate investigation into practice is an essential of the National Association for Professional Development Schools' defining elements of a Professional Development School (PDS). This article reports on the pilot efforts of one PDS as it initiated deliberate investigation through action research with a small group of teacher candidates. The…

  18. From Fiction to Fact to Potential Action: Generating Prosocial Attitudes and Behaviors Using Young Adult Literature

    Science.gov (United States)

    Hays, Alice

    2017-01-01

    This dissertation investigates the impact reading Young Adult Literature (YAL) has on students' empathetic responses as well as their capacity to take action regarding a social justice issue chosen by the student. Drawing on data from a 10th grade honors classroom at a Title 1 school in the Southwest, this ethnographic case study investigates how…

  19. New Sides of Aldosterone Action in Cardiovascular System as Potential Targets for Therapeutic Intervention.

    Science.gov (United States)

    Kolodziejczyk, Patrycjusz; Gromotowicz-Poplawska, Anna; Aleksiejczuk, Michal; Chabielska, Ewa; Tutka, Piotr; Miltyk, Wojciech

    2018-03-26

    Aldosterone, the main mineralocorticoid hormone, plays a crucial role in the regulation of electrolyte homeostasis and blood pressure. Although, this role is undoubtedly important, it is not a hormonal action that attracts the most attention. Aldosterone seems to be very important important as a local messenger in the pathology of cardiovascular diseases (CVD). In the last few years, the attention was focused on the correlation between raised aldosterone level and increased risk of cardiovascular events. It has been demonstrated that aldosterone contributes to fibrosis, inflammation, endothelial dysfunction, fibrinolytic disordes, and oxidative stress leading to CVD development and progression. It used to be thought that the effects of aldosterone are mediated via classic nuclear receptors - mineralocorticoid receptors (MR). Now we know that the mechanism of aldosterone action in cardiovascular system is much more complex, since experimental and clinical studies indicate that MR blockade may be not sufficient to abolish aldosterone-incuced harmful effects in the cardiovascular system. Therefore, the involvement of some other than MR, receptors and factors is suggested. Moreover, in addition to the generally known genomic action of aldosterone, which involves MR activation, the nongenomic pathways are postulated in the mode of hormone action. More and more attention is focused on the membrane-coupled receptors, which mediate the rapid effects of aldosterone and have been already confirmed in different cells and tissues of a cardiovascular system. The confirmation of multiple mechanisms of aldosterone action opens a new perspective for more effective therapeutic intervention in aldosterone-related CVD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Real time estimation of generation, extinction and flow of muscle fibre action potentials in high density surface EMG.

    Science.gov (United States)

    Mesin, Luca

    2015-02-01

    Developing a real time method to estimate generation, extinction and propagation of muscle fibre action potentials from bi-dimensional and high density surface electromyogram (EMG). A multi-frame generalization of an optical flow technique including a source term is considered. A model describing generation, extinction and propagation of action potentials is fit to epochs of surface EMG. The algorithm is tested on simulations of high density surface EMG (inter-electrode distance equal to 5mm) from finite length fibres generated using a multi-layer volume conductor model. The flow and source term estimated from interference EMG reflect the anatomy of the muscle, i.e. the direction of the fibres (2° of average estimation error) and the positions of innervation zone and tendons under the electrode grid (mean errors of about 1 and 2mm, respectively). The global conduction velocity of the action potentials from motor units under the detection system is also obtained from the estimated flow. The processing time is about 1 ms per channel for an epoch of EMG of duration 150 ms. A new real time image processing algorithm is proposed to investigate muscle anatomy and activity. Potential applications are proposed in prosthesis control, automatic detection of optimal channels for EMG index extraction and biofeedback. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Feature-Specific Event-Related Potential Effects to Action- and Sound-Related Verbs during Visual Word Recognition.

    Science.gov (United States)

    Popp, Margot; Trumpp, Natalie M; Kiefer, Markus

    2016-01-01

    Grounded cognition theories suggest that conceptual representations essentially depend on modality-specific sensory and motor systems. Feature-specific brain activation across different feature types such as action or audition has been intensively investigated in nouns, while feature-specific conceptual category differences in verbs mainly focused on body part specific effects. The present work aimed at assessing whether feature-specific event-related potential (ERP) differences between action and sound concepts, as previously observed in nouns, can also be found within the word class of verbs. In Experiment 1, participants were visually presented with carefully matched sound and action verbs within a lexical decision task, which provides implicit access to word meaning and minimizes strategic access to semantic word features. Experiment 2 tested whether pre-activating the verb concept in a context phase, in which the verb is presented with a related context noun, modulates subsequent feature-specific action vs. sound verb processing within the lexical decision task. In Experiment 1, ERP analyses revealed a differential ERP polarity pattern for action and sound verbs at parietal and central electrodes similar to previous results in nouns. Pre-activation of the meaning of verbs in the preceding context phase in Experiment 2 resulted in a polarity-reversal of feature-specific ERP effects in the lexical decision task compared with Experiment 1. This parallels analogous earlier findings for primed action and sound related nouns. In line with grounded cognitions theories, our ERP study provides evidence for a differential processing of action and sound verbs similar to earlier observation for concrete nouns. Although the localizational value of ERPs must be viewed with caution, our results indicate that the meaning of verbs is linked to different neural circuits depending on conceptual feature relevance.

  2. The potential for multi-disciplinary primary health care services to take action on the social determinants of health: actions and constraints.

    Science.gov (United States)

    Baum, Frances E; Legge, David G; Freeman, Toby; Lawless, Angela; Labonté, Ronald; Jolley, Gwyneth M

    2013-05-10

    The Commission on the Social Determinants of Health and the World Health Organization have called for action to address the social determinants of health. This paper considers the extent to which primary health care services in Australia are able to respond to this call. We report on interview data from an empirical study of primary health care centres in Adelaide and Alice Springs, Australia. Sixty-eight interviews were held with staff and managers at six case study primary health care services, regional health executives, and departmental funders to explore how their work responded to the social determinants of health and the dilemmas in doing so. The six case study sites included an Aboriginal Community Controlled Organisation, a sexual health non-government organisation, and four services funded and managed by the South Australian government. While respondents varied in the extent to which they exhibited an understanding of social determinants most were reflexive about the constraints on their ability to take action. Services' responses to social determinants included delivering services in a way that takes account of the limitations individuals face from their life circumstances, and physical spaces in the primary health care services being designed to do more than simply deliver services to individuals. The services also undertake advocacy for policies that create healthier communities but note barriers to them doing this work. Our findings suggest that primary health care workers are required to transverse "dilemmatic space" in their work. The absence of systematic supportive policy, frameworks and structure means that it is hard for PHC services to act on the Commission on the Social Determinants of Health's recommendations. Our study does, however, provide evidence of the potential for PHC services to be more responsive to social determinants given more support and by building alliances with communities and social movements. Further research on the value

  3. Microelectrode array measurement of potassium ion channel remodeling on the field action potential duration in rapid atrial pacing rabbits model.

    Science.gov (United States)

    Sun, Juan; Yan, Huang; Wugeti, Najina; Guo, Yujun; Zhang, Ling; Ma, Mei; Guo, Xingui; Jiao, Changan; Xu, Wenli; Li, Tianqi

    2015-01-01

    Atrial fibrillation (AF) arises from abnormalities in atrial structure and electrical activity. Microelectrode arrays (MEA) is a real-time, nondestructive measurement of the resting and action potential signal, from myocardial cells, to the peripheral circuit of electrophysiological activity. This study examined the field action potential duration (fAPD) of the right atrial appendage (RAA) by MEA in rapid atrial pacing (RAP) in the right atrium of rabbits. In addition, this study also investigated the effect of potassium ion channel blockers on fAPD. 40 New Zealand white rabbits of either sex were randomly divided into 3 groups: 1) the control, 2) potassium ion channel blocker (TEA, 4-Ap and BaCl2), and 3) amiodarone groups. The hearts were quickly removed and right atrial appendage sectioned (slice thickness 500 μm). Each slice was perfused with Tyrode's solution and continuously stimulated for 30 minutes. Sections from the control group were superfused with Tyrode's solution for 10 minutes, while the blocker groups and amiodarone were both treated with their respective compounds for 10 minutes each. The fAPD of RAA and action field action potential morphology were measured using MEA. In non-pace (control) groups, fAPD was 188.33 ± 18.29 ms after Tyrode's solution superfusion, and 173.91 ± 6.83 ms after RAP. In pace/potassium ion channel groups, TEA and BaCl2 superfusion prolonged atrial field action potential (fAPD) (control vs blocker: 176.67 ± 8.66 ms vs 196.11 ± 10.76 ms, 182.22 ± 12.87 ms vs 191.11 ± 13.09 ms with TEA and BaCl2 superfusion, respectively, P action potential in animal heart slices. After superfusing potassium ion channel blockers, fAPD was prolonged. These results suggest that Ito, IKur and IK1 remodel and mediate RAP-induced atrial electrical remodeling. Amiodarone alter potassium ion channel activity (Ito, IKur, IK1 and IKs), shortening fAPD.

  4. Assessing transformational change potential: the case of the Tunisian cement Nationally Appropriate Mitigation Action (NAMA)

    DEFF Research Database (Denmark)

    Boodoo, Zyaad; Olsen, Karen Holm

    2018-01-01

    and documentation gathered during field work in Tunisia 2014–2015. The study finds that the NAMA design is not likely to lead to transformational change of the cement sector, since underlying factors accounting for lock-in are not properly tackled. Although the NAMA has enabled new and promising sectoral......To effectively address the root causes of carbon lock-in across developing countries, Nationally Appropriate Mitigation Actions (NAMAs) with transformational change characteristics are being supported by donors and finance mechanisms as a means to achieve ambitious nationally determined...... contributions (NDCs). However, there is still a scarcity of empirical studies on how transformational change policies and actions are designed and supported in practice. This article addresses such a gap in knowledge by combining theoretical insights from the multi-level perspective and transitions management...

  5. Biosynthesis of silver nanoparticles using Sida acuta extract for antimicrobial actions and corrosion inhibition potential.

    Science.gov (United States)

    Idrees, Muhammad; Batool, Saima; Kalsoom, Tanzila; Raina, Sadaf; Sharif, Hafiz Muhammad Adeel; Yasmeen, Summera

    2018-02-12

    Nanotechnology exhibits a multidisciplinary area and gained interests for researchers. Nanoparticles produced via physical and chemical methods affects ecosystem drastically. Green synthesis is the charming technique that is inexpensive and safe for the environment. This study aimed to explore the antibacterial actions of as-synthesized silver nanoparticles (Ag-NPs) against Escherichia coli, Staphylococcus aureus and Streptococcus faecalis. Also, the anti-corrosion actions confirmed that the Ag-NPs proved as good inhibitors. In this way, Ag-NPs were prepared via biosynthesis technique by consuming the ground leaves and stem of 'Sida acuta' as a capping agent. The Ag-NPs were formed by irradiation of the aqueous solution of silver nitrate (AgNO 3 ) with extract of S. acuta stem and leaves. The as-synthesized reaction mixture of Ag-NPs was found to exhibit an absorbance band at 446-447 nm, by an UV/VIS spectrophotometer, which is a characteristic of Ag-NPs due to the surface plasmon resonance absorption band. The X-ray diffraction and transmission electron microscopy (TEM) were used for the confirmation of Ag-NPs' variety dimension, morphology and dispersion. The infrared spectra confirmed the bio-fabrication of the Ag-NPs displayed the existence of conceivable functional groups responsible for the bio-reduction and capping. The antimicrobial actions were measured and the zone of inhibition was compared with standard antibiotics.

  6. Diosgenin, 4-hydroxyisoleucine, and fiber from fenugreek: mechanisms of actions and potential effects on metabolic syndrome.

    Science.gov (United States)

    Fuller, Scott; Stephens, Jacqueline M

    2015-03-01

    Metabolic syndrome and its complications continue to rise in prevalence and show no signs of abating in the immediate future. Therefore, the search for effective treatments is a high priority in biomedical research. Products derived from botanicals have a time-honored history of use in the treatment of metabolic diseases including type 2 diabetes. Trigonella foenum-graecum, commonly known as fenugreek, is an annual herbaceous plant that has been a staple of traditional herbal medicine in many cultures. Although fenugreek has been studied in both clinical and basic research settings, questions remain about its efficacy and biologic mechanisms of action. Diosgenin, 4-hydroxyisoleucine, and the fiber component of the plant are the most intensively studied bioactive constituents present in fenugreek. These compounds have been demonstrated to exert beneficial effects on several physiologic markers including glucose tolerance, inflammation, insulin action, liver function, blood lipids, and cardiovascular health. Although insights into the molecular mechanisms underlying the favorable effects of fenugreek have been gained, we still do not have definitive evidence establishing its role as a therapeutic agent in metabolic disease. This review aims to summarize the currently available evidence on the physiologic effects of the 3 best-characterized bioactive compounds of fenugreek, with particular emphasis on biologic mechanisms of action relevant in the context of metabolic syndrome. © 2015 American Society for Nutrition.

  7. A multiscale approach to modelling electrochemical processes occurring across the cell membrane with application to transmission of action potentials.

    Science.gov (United States)

    Richardson, G

    2009-09-01

    By application of matched asymptotic expansions, a simplified partial differential equation (PDE) model for the dynamic electrochemical processes occurring in the vicinity of a membrane, as ions selectively permeate across it, is formally derived from the Poisson-Nernst-Planck equations of electrochemistry. It is demonstrated that this simplified model reduces itself, in the limit of a long thin axon, to the cable equation used by Hodgkin and Huxley to describe the propagation of action potentials in the unmyelinated squid giant axon. The asymptotic reduction from the simplified PDE model to the cable equation leads to insights that are not otherwise apparent; these include an explanation of why the squid giant axon attains a diameter in the region of 1 mm. The simplified PDE model has more general application than the Hodgkin-Huxley cable equation and can, e.g. be used to describe action potential propagation in myelinated axons and neuronal cell bodies.

  8. [Hardware Implementation of Numerical Simulation Function of Hodgkin-Huxley Model Neurons Action Potential Based on Field Programmable Gate Array].

    Science.gov (United States)

    Wang, Jinlong; Lu, Mai; Hu, Yanwen; Chen, Xiaoqiang; Pan, Qiangqiang

    2015-12-01

    Neuron is the basic unit of the biological neural system. The Hodgkin-Huxley (HH) model is one of the most realistic neuron models on the electrophysiological characteristic description of neuron. Hardware implementation of neuron could provide new research ideas to clinical treatment of spinal cord injury, bionics and artificial intelligence. Based on the HH model neuron and the DSP Builder technology, in the present study, a single HH model neuron hardware implementation was completed in Field Programmable Gate Array (FPGA). The neuron implemented in FPGA was stimulated by different types of current, the action potential response characteristics were analyzed, and the correlation coefficient between numerical simulation result and hardware implementation result were calculated. The results showed that neuronal action potential response of FPGA was highly consistent with numerical simulation result. This work lays the foundation for hardware implementation of neural network.

  9. Dynamic characteristics of rotating pretwisted clamped-clamped beam under thermal stress

    International Nuclear Information System (INIS)

    Zhang, Bo; Li, Yueming; Lu, Wei Zhen

    2016-01-01

    Effects of thermal stress on the vibration characteristics, buckling limit and critical speed of a rotating pretwisted beam clamped to rigid hub at a stagger angle were investigated. By considering the work done by thermal stress, the thermal influence on stiffness matrix was introduced in the dynamic model. The motion equations were derived based on Lagrange equation by employing three pure Cartesian deformation variables combined with nonlinear von Karman strain formula. Numerical investigations studied the modal characteristics of the beam. Numerical results calculated from a commercial finite element code and obtained with the present modeling method were in good agreement with the previous results reported in the literature. The combined softening effects due to the thermal stress and the rotation motion were observed. Furthermore, it is shown that the inclusion of thermal stress is necessary for blades operating under a high temperature field. Buckling thermal loads and the critical rotating speed were calculated through solving the corresponding nonlinear equations numerically, and some pertinent conclusions are outlined. It is also found that the peak value position of the first mode shape approaches to the tip of blade with the increment of rotating speed and hub radius. However, the variation in the environment temperature causes only a slight alteration in the mode shape

  10. Dynamic characteristics of rotating pretwisted clamped-clamped beam under thermal stress

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Bo; Li, Yueming [State Key Laboratory for Strength and Vibration of Mechanical Structures, Shaanxi Key Laboratory of Environment and Control for Flight Vehicle, School of Aerospace, Xi' an Jiaotong UniversityXi' an (China); Lu, Wei Zhen [Dept. of Civil and Architectural Engineering, City University of Hong Kong, Hong Kong (China)

    2016-09-15

    Effects of thermal stress on the vibration characteristics, buckling limit and critical speed of a rotating pretwisted beam clamped to rigid hub at a stagger angle were investigated. By considering the work done by thermal stress, the thermal influence on stiffness matrix was introduced in the dynamic model. The motion equations were derived based on Lagrange equation by employing three pure Cartesian deformation variables combined with nonlinear von Karman strain formula. Numerical investigations studied the modal characteristics of the beam. Numerical results calculated from a commercial finite element code and obtained with the present modeling method were in good agreement with the previous results reported in the literature. The combined softening effects due to the thermal stress and the rotation motion were observed. Furthermore, it is shown that the inclusion of thermal stress is necessary for blades operating under a high temperature field. Buckling thermal loads and the critical rotating speed were calculated through solving the corresponding nonlinear equations numerically, and some pertinent conclusions are outlined. It is also found that the peak value position of the first mode shape approaches to the tip of blade with the increment of rotating speed and hub radius. However, the variation in the environment temperature causes only a slight alteration in the mode shape.

  11. Natural Vibration Analysis of Clamped Rectangular Orthotropic Plates

    Science.gov (United States)

    dalaei, m.; kerr, a. d.

    The natural vibrations of clamped rectangular orthotropic plates are analyzed using the extended Kantorovich method. The developed iterative scheme converges very rapidly to the final result. The obtained natural frequencies are evaluated for a square plate made of Kevlar 49 Epoxy and the obtained results are compared with those published by Kanazawa and Kawai, and by Leissa. The agreement was found to be very close. As there are no exact analytical solutions for clamped rectangular plates, the generated closed form expression for the natural modes, and the corresponding natural frequencies, are very suitable for use in engineering analyses.

  12. Improved DNA clamps by stacking to adjacent nucleobases

    DEFF Research Database (Denmark)

    Fatthalla, M.I.; Pedersen, Erik Bjerregaard

    2012-01-01

    Three or four aromatic rings interconnected by acetylene bridges form a stiff conjugated system with sufficient conformational freedom to make it useful to link together the two strands of a DNA clamp. Upon targeting a ssDNA, the conformational flexibility allows better stacking of the linker...... to the underlying non-planar base triplet in the formed triplex. This type of triplexes has a substantially higher thermal melting temperature which can be further improved by inserting locked nucleic acids (LNAs) in the Hoogsteen part of the clamp. An extremely high sensitivity to mismatches is observed...

  13. 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.

  14. Robotic multi-well planar patch-clamp for native and primary mammalian cells

    Science.gov (United States)

    Milligan, Carol J; Li, Jing; Sukumar, Piruthivi; Majeed, Yasser; Dallas, Mark L; English, Anne; Emery, Paul; Porter, Karen E; Smith, Andrew M; McFadzean, Ian; Beccano-Kelly, Dayne; Bahnasi, Yahya; Cheong, Alex; Naylor, Jacqueline; Zeng, Fanning; Liu, Xing; Gamper, Nikita; Jiang, Lin-Hua; Pearson, Hugh A; Peers, Chris; Robertson, Brian; Beech, David J

    2009-01-01

    Multi-well robotic planar patch-clamp has become common in drug development and safety programmes because it enables efficient and systematic testing of compounds against ion channels during voltage-clamp. It has not, however, been adopted significantly in other important areas of ion channel research, where conventional patch-clamp remains the favoured method. Here we show the wider potential of the multi-well approach with the capability for efficient intracellular solution exchange, describing protocols and success rates for recording from a range of native and primary mammalian cells derived from blood vessels, arthritic joints, and the immune and central nervous systems. The protocol involves preparing a suspension of single cells to be dispensed robotically into 4-8 microfluidic chambers each containing a glass chip with a small aperture. Under automated control, giga-seals and whole-cell access are achieved followed by pre-programmed routines of voltage paradigms and fast extracellular or intracellular solution exchange. Recording from 48 chambers usually takes 1-6 hr depending on the experimental design and yields 16-33 cell recordings. PMID:19197268

  15. A simulation of T-wave alternans vectocardiographic representation performed by changing the ventricular heart cells action potential duration.

    Science.gov (United States)

    Janusek, D; Kania, M; Zaczek, R; Zavala-Fernandez, H; Maniewski, R

    2014-04-01

    The presence of T wave alternans (TWA) in the surface ECG signals has been recognized as a marker of electrical instability, and is hypothesized to be related to patients at increased risk for ventricular arrhythmias. In this paper we present a TWA simulation study. The TWA phenomenon was simulated by changing the duration of the ventricular heart cells action potential. The magnitude was calculated in the surface ECG with the use of the time domain method. The spatially concordant TWA, where during one heart beat all ventricular cells display a short-duration action potential and during the next beat they exhibit a long-duration action potential, as well as the discordant TWA, where at least one region is out of phase, was simulated. The vectocardiographic representation was employed. The obtained results showed a high level of T-loop pattern and location disturbances connected to the discordant TWA simulation in contrast to the concordant one. This result may be explained by the spatial heterogeneity of the ventricular repolarization process, which could be higher for the discordant TWA than for the concordant TWA. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Coupled iterated map models of action potential dynamics in a one-dimensional cable of cardiac cells

    International Nuclear Information System (INIS)

    Wang Shihong; Xie Yuanfang; Qu Zhilin

    2008-01-01

    Low-dimensional iterated map models have been widely used to study action potential dynamics in isolated cardiac cells. Coupled iterated map models have also been widely used to investigate action potential propagation dynamics in one-dimensional (1D) coupled cardiac cells, however, these models are usually empirical and not carefully validated. In this study, we first developed two coupled iterated map models which are the standard forms of diffusively coupled maps and overcome the limitations of the previous models. We then determined the coupling strength and space constant by quantitatively comparing the 1D action potential duration profile from the coupled cardiac cell model described by differential equations with that of the coupled iterated map models. To further validate the coupled iterated map models, we compared the stability conditions of the spatially uniform state of the coupled iterated maps and those of the 1D ionic model and showed that the coupled iterated map model could well recapitulate the stability conditions, i.e. the spatially uniform state is stable unless the state is chaotic. Finally, we combined conduction into the developed coupled iterated map model to study the effects of coupling strength on wave stabilities and showed that the diffusive coupling between cardiac cells tends to suppress instabilities during reentry in a 1D ring and the onset of discordant alternans in a periodically paced 1D cable

  17. Small-conductance calcium-activated potassium (SK) channels contribute to action potential repolarization in human atria

    DEFF Research Database (Denmark)

    Skibsbye, Lasse; Poulet, Claire; Diness, Jonas Goldin

    2014-01-01

    (+) currents by ∼15% and prolonged action potential duration (APD), but no effect was observed in myocytes from AF patients. In trabeculae muscle strips from right atrial appendages of SR patients, both compounds increased APD and effective refractory period, and depolarized the resting membrane potential......, while only NS8593 induced these effects in tissue from AF patients. SK channel inhibition did not alter any electrophysiological parameter in human interventricular septum tissue. CONCLUSIONS: SK channels are present in human atria where they participate in repolarization. SK2 and SK3 were down...

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

    Science.gov (United States)

    Berg, Rune W.; Stauning, Marius Tving; Sørensen, Jakob Balslev; Jahnsen, Henrik

    2017-04-01

    The action potential (AP) is an electrical impulse elicited by depolarization of the neuronal membrane from the resting membrane potential (around -70 mV ). It propagates along the axon, allowing for rapid and distant communication. Recently, it was claimed that two APs traveling in opposite direction will pass unhindered through each other (penetrate) upon collision [Gonzalez-Perez et al.Phys. Rev. X 4, 031047 (2014), 10.1103/PhysRevX.4.031047]. We tested this claim under carefully controlled conditions and found that we cannot reproduce penetration. Instead, APs consistently annihilated upon collision. This is consistent with a vast body of literature.

  19. Conservation laws of wave action and potential enstrophy for Rossby waves in a stratified atmosphere

    Science.gov (United States)

    Straus, D. M.

    1983-01-01

    The evolution of wave energy, enstrophy, and wave motion for atmospheric Rossby waves in a variable mean flow are discussed from a theoretical and pedagogic standpoint. In the absence of mean flow gradients, the wave energy density satisfies a local conservation law, with the appropriate flow velocity being the group velocity. In the presence of mean flow variations, wave energy is not conserved, but wave action is, provided the mean flow is independent of longitude. Wave enstrophy is conserved for arbitrary variations of the mean flow. Connections with Eliassen-Palm flux are also discussed.

  20. 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...

  1. Potentiation of E-4031-induced torsade de pointes by HMR1556 or ATX-II is not predicted by action potential short-term variability or triangulation.

    Science.gov (United States)

    Michael, G; Dempster, J; Kane, K A; Coker, S J

    2007-12-01

    Torsade de pointes (TdP) can be induced by a reduction in cardiac repolarizing capacity. The aim of this study was to assess whether IKs blockade or enhancement of INa could potentiate TdP induced by IKr blockade and to investigate whether short-term variability (STV) or triangulation of action potentials preceded TdP. Experiments were performed in open-chest, pentobarbital-anaesthetized, alpha 1-adrenoceptor-stimulated, male New Zealand White rabbits, which received three consecutive i.v. infusions of either the IKr blocker E-4031 (1, 3 and 10 nmol kg(-1) min(-1)), the IKs blocker HMR1556 (25, 75 and 250 nmol kg(-1) min(-1)) or E-4031 and HMR1556 combined. In a second study rabbits received either the same doses of E-4031, the INa enhancer, ATX-II (0.4, 1.2 and 4.0 nmol kg(-1)) or both of these drugs. ECGs and epicardial monophasic action potentials were recorded. HMR1556 alone did not cause TdP but increased E-4031-induced TdP from 25 to 80%. ATX-II alone caused TdP in 38% of rabbits, as did E-4031; 75% of rabbits receiving both drugs had TdP. QT intervals were prolonged by all drugs but the extent of QT prolongation was not related to the occurrence of TdP. No changes in STV were detected and triangulation was only increased after TdP occurred. Giving modulators of ion channels in combination substantially increased TdP but, in this model, neither STV nor triangulation of action potentials could predict TdP.

  2. Anaesthetics stop diverse plant organ movements, affect endocytic vesicle recycling and ROS homeostasis, and block action potentials in Venus flytraps.

    Science.gov (United States)

    Yokawa, K; Kagenishi, T; Pavlovic, A; Gall, S; Weiland, M; Mancuso, S; Baluška, F

    2017-12-11

    Anaesthesia for medical purposes was introduced in the 19th century. However, the physiological mode of anaesthetic drug actions on the nervous system remains unclear. One of the remaining questions is how these different compounds, with no structural similarities and even chemically inert elements such as the noble gas xenon, act as anaesthetic agents inducing loss of consciousness. The main goal here was to determine if anaesthetics affect the same or similar processes in plants as in animals and humans. A single-lens reflex camera was used to follow organ movements in plants before, during and after recovery from exposure to diverse anaesthetics. Confocal microscopy was used to analyse endocytic vesicle trafficking. Electrical signals were recorded using a surface AgCl electrode. Mimosa leaves, pea tendrils, Venus flytraps and sundew traps all lost both their autonomous and touch-induced movements after exposure to anaesthetics. In Venus flytrap, this was shown to be due to the loss of action potentials under diethyl ether anaesthesia. The same concentration of diethyl ether immobilized pea tendrils. Anaesthetics also impeded seed germination and chlorophyll accumulation in cress seedlings. Endocytic vesicle recycling and reactive oxygen species (ROS) balance, as observed in intact Arabidopsis root apex cells, were also affected by all anaesthetics tested. Plants are sensitive to several anaesthetics that have no structural similarities. As in animals and humans, anaesthetics used at appropriate concentrations block action potentials and immobilize organs via effects on action potentials, endocytic vesicle recycling and ROS homeostasis. Plants emerge as ideal model objects to study general questions related to anaesthesia, as well as to serve as a suitable test system for human anaesthesia. © The Authors 2017. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. 21 CFR 882.5175 - Carotid artery clamp.

    Science.gov (United States)

    2010-04-01

    ... (the principal artery in the neck that supplies blood to the brain) and has a removable adjusting mechanism that protrudes through the skin of the patient's neck. The clamp is used to occlude the patient's... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...

  4. Estimates for lower order eigenvalues of a clamped plate problem

    OpenAIRE

    Cheng, Qing-Ming; Huang, Guangyue; Wei, Guoxin

    2009-01-01

    For a bounded domain $\\Omega$ in a complete Riemannian manifold $M^n$, we study estimates for lower order eigenvalues of a clamped plate problem. We obtain universal inequalities for lower order eigenvalues. We would like to remark that our results are sharp.

  5. 33 CFR 183.532 - Clips, straps, and hose clamps.

    Science.gov (United States)

    2010-07-01

    ... resistant material; and (2) Not cut or abrade the fuel line. (b) If tested in accordance with the fire test under § 183.590, a hose clamp installed on a fuel line system requiring metallic fuel lines or “USCG... (CONTINUED) BOATING SAFETY BOATS AND ASSOCIATED EQUIPMENT Fuel Systems Equipment Standards § 183.532 Clips...

  6. Euglycemic clamp insulin sensitivity and longitudinal systolic blood pressure

    DEFF Research Database (Denmark)

    Petrie, John R; Malik, Muhammad Omar; Balkau, Beverley

    2013-01-01

    and Cardiovascular disease (RISC) study, we measured insulin sensitivity (M/I) using the euglycemic clamp technique in 1073 healthy European adults (587 women, 486 men) aged 30 to 60 years followed up 3 years later. Systolic BP (SBP) at baseline was higher in insulin-resistant women (ie, those in the low sex...

  7. Biphasic response of action potential duration to metabolic inhibition in rabbit and human ventricular myocytes: role of transient outward current and ATP-regulated potassium current

    NARCIS (Netherlands)

    Verkerk, A. O.; Veldkamp, M. W.; van Ginneken, A. C.; Bouman, L. N.

    1996-01-01

    Inhibition of cell metabolism is associated with significant changes in action potential duration. The aim of this study was to investigate the time course of the changes in action potential duration during metabolic inhibition and to determine what changes in membrane currents are responsible. The

  8. Matrix metalloproteinase-13 downregulation and potential cartilage protective action of the Korean Red Ginseng preparation

    Directory of Open Access Journals (Sweden)

    Je Hyeong Lee

    2015-01-01

    Conclusion: Some preparations from Korean Red Ginseng and ginseng leaves, particularly GDF/F4, may possess the protective activity against cartilage degradation in joint disorders, and may have potential as new therapeutic agents.

  9. Assessing potential targets of calcium action in light-modulated gravitropism

    Science.gov (United States)

    Roux, S. J.

    1995-01-01

    Light, through the mediation of the pigment phytochrome, modulates the gravitropic response of the shoots and roots of many plants. The transduction of both light and gravity stimuli appears to involve Ca(2+)-regulated steps, one or more of which may represent points of intersection between the two transduction chains. To be confident that Ca2+ plays a critical role in stimulus-response coupling for gravitropism, it will be important to identify specific targets of Ca2+ action whose function can be clearly linked to the regulation of growth. Calcium typically exerts its influence on cell metabolism through binding to and activating key regulatory proteins. The three best characterized of these proteins in plants are the calmodulins, calcium-dependent protein kinases, and annexins. In this review we summarize what is known about the structure and function of these proteins and speculate on how their activation by Ca2+ could influence the differential growth response of gravitropism.

  10. Methodological considerations for characterizing potential antioxidant actions of bioactive components in plant foods.

    Science.gov (United States)

    Aruoma, Okezie I

    2003-01-01

    The study of free radicals and antioxidants in biology is producing medical revolution that promises a new age of health and disease management. From prevention of the oxidative reactions in foods, pharmaceuticals and cosmetics to the role of reactive oxygen species (ROS) in chronic degenerative diseases including cancer, autoimmune, inflammatory, cardiovascular and neurodegenerative (e.g. Alzheimer's disease, Parkinson's disease, multiple sclerosis, Downs syndrome) and aging challenges continue to emerge from difficulties associated with methods used in evaluating antioxidant actions in vivo. Our interest presently is focused on development of neurodegeneration models based on the integrity of neuronal cells in the central nervous system and how they are protected by antioxidants when challenged by neurotoxins as well as Fenton chemistry models based on the profile of polyunsaturated fatty acids (PUFAs) for the assessment of antioxidant actions in vivo. Use continues to be made of several in vitro analytical tools to characterise the antioxidant propensity of bioactive compounds in plant foods and supplements. For example, the oxygen radical absorbance capacity (ORAC), ferric reducing antioxidant power (FRAP), total oxidant scavenging capacity (TOSC), the deoxyribose assay, assays involving oxidative DNA damage, assays involving reactive nitrogen intermediates (e.g. ONOO(-)), Trolox equivalent antioxidant capacity (TEAC) and the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. There is need to agree governance on in vitro antioxidant methods based on an understanding of the mechanisms involved. Because some of the assays are done in non-physiological pH values, it is impossible to extrapolate the results to physiological environment. The consensus of opinion is that a mix of these tools should be used in assessing the antioxidant activities in vitro. The proof of bio-efficacy must emanate from application of reliable in vivo models where markers of baseline oxidative

  11. HMGB1 Inhibition During Zymosan-Induced Inflammation: The Potential Therapeutic Action of Riboflavin.

    Science.gov (United States)

    Mazur-Bialy, Agnieszka Irena; Pocheć, Ewa

    2016-04-01

    Sepsis, also known as systemic inflammatory response syndrome, is a life-threatening condition caused by a pathogenic agent and leading to multiple organ dysfunction syndrome. One of the factors responsible for the excessive intensification of the inflammatory response in the course of inflammation is high-mobility group protein B1 (HMGB1). HMG-1 is a nuclear protein which, after being released to the intercellular space, has a highly pro-inflammatory effect and acts as a late mediator of lethal damage. The purpose of this study was to examine whether the anti-inflammatory action of riboflavin is accompanied by inhibition of HMGB1 release during peritoneal inflammation and zymosan stimulation of macrophages. Peritonitis was induced in male BALB/c and C57BL/6J mice via intraperitoneal injection of zymosan (40 mg/kg). RAW 264.7 macrophages were activated with zymosan (250 µg/ml). Riboflavin (mice, 50 mg/kg; RAW 264.7, 25 µg/ml) was administered 30 min before zymosan, simultaneously with, or 2, 4, 6 h after zymosan. Additionally, mRNA expression of HMGB1 and its intracellular and serum levels were evaluated. The research showed that riboflavin significantly reduces both the expression and the release of HMGB1; however, the effect of riboflavin was time-dependent. The greatest efficacy was found when riboflavin was given 30 min prior to zymosan, and also 2 and 4 h (C57BL/6J; RAW 264.7) or 4 and 6 h (BALB/c) after zymosan. Research showed that riboflavin influences the level of HMGB1 released in the course of inflammation; however, further study is necessary to determine its mechanisms of action.

  12. Pathological prolongation of action potential duration as a cause of the reduced alpha-adrenoceptor-mediated negative inotropy in streptozotocin-induced diabetic mice myocardium.

    Science.gov (United States)

    Kanae, Haruna; Hamaguchi, Shogo; Wakasugi, Yumi; Kusakabe, Taichi; Kato, Keisuke; Namekata, Iyuki; Tanaka, Hikaru

    2017-11-01

    Effect of pathological prolongation of action potential duration on the α-adrenoceptor-mediated negative inotropy was studied in streptozotocin-induced diabetic mice myocardium. In streptozotocin-treated mouse ventricular myocardium, which had longer duration of action potential than that in control mice, the negative inotropic response induced by phenylephrine was smaller than that in control mice. 4-Aminopyridine prolonged the action potential duration and decreased the negative inotropy in control mice. Cromakalim shortened the action potential duration and increased the negative inotropy in streptozotocin-treated mice. These results suggest that the reduced α-adrenoceptor-mediated inotropy in the diabetic mouse myocardium is partly due to its prolonged action potential. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  13. Potential Molecular Mechanisms on the Role of the Sigma-1 Receptor in the Action of Cocaine and Methamphetamine

    Science.gov (United States)

    Yasui, Yuko; Su, Tsung-Ping

    2016-01-01

    The sigma-1 receptor (Sig-1R) is an endoplasmic reticulum membrane protein that involves a wide range of physiological functions. The Sig-1R has been shown to bind psychostimulants including cocaine and methamphetamine (METH) and thus has been implicated in the actions of those psychostimulants. For example, it has been demonstrated that the Sig-1R antagonists mitigate certain behavioral and cellular effects of psychostimulants including hyperactivity and neurotoxicity. Thus, the Sig-1R has become a potential therapeutic target of medication development against drug abuse that differs from traditional monoamine-related strategies. In this review, we will focus on the molecular mechanisms of the Sig-1R and discuss in such a manner with a hope to further understand or unveil unexplored relations between the Sig-1R and the actions of cocaine and METH, particularly in the context of cellular biological relevance. PMID:27088037

  14. The actions of mdivi-1, an inhibitor of mitochondrial fission, on rapidly activating delayed-rectifier K⁺ current and membrane potential in HL-1 murine atrial cardiomyocytes.

    Science.gov (United States)

    So, Edmund Cheung; Hsing, Chung-Hsi; Liang, Chia-Hua; Wu, Sheng-Nan

    2012-05-15

    Mdivi-1 is an inhibitor of dynamin related protein 1- (drp1)-mediated mitochondrial fission. However, the mechanisms through which this compound interacts directly with ion currents in heart cells remain unknown. In this study, its effects on ion currents and membrane potential in murine HL-1 cardiomyocytes were investigated. In whole-cell recordings, the addition of mdivi-1 decreased the amplitude of tail current (I(tail)) for the rapidly activating delayed-rectifier K⁺ current (I(Kr)) in a concentration-dependent manner with an IC₅₀ value at 11.6 μM, a value that resembles the inhibition requirement for mitochondrial division. It shifted the activation curve of I(tail) to depolarized voltages with no change in the gating charge. However, mdivi-1 did not alter the rate of recovery from current inactivation. In cell-attached configuration, mdivi-1 inside the pipette suppressed the activity of acetylcholine-activated K⁺ channels without modifying the single-channel conductance. Mdivi-1 (30 μM) slightly depressed the peak amplitude of Na⁺ current with no change in the overall current-voltage relationship. Under current-clamp recordings, addition of mdivi-1 resulted in prolongation for the duration of action potentials (APs) and to increase the firing of spontaneous APs in HL-1 cells. Similarly, in pituitary GH₃ cells, mdivi-1 was effective in directly suppressing the amplitude of ether-à-go-go-related gene-mediated K⁺ current. Therefore, the lengthening of AP duration and increased firing of APs caused by mdivi-1 can be primarily explained by its inhibition of these K⁺ channels enriched in heart cells. The observed effects of mdivi-1 on ion currents were direct and not associated with its inhibition of mitochondrial division. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Metabotropic action of postsynaptic kainate receptors triggers hippocampal long-term potentiation

    Czech Academy of Sciences Publication Activity Database

    Petrovič, Miloš; da Silva, S. V.; Clement, J. P.; Vyklický ml., Ladislav; Mulle, C.; González-González, I. M.; Henley, J. M.

    2017-01-01

    Roč. 20, č. 4 (2017), s. 529-539 ISSN 1097-6256 R&D Projects: GA ČR(CZ) GA17-02300S Institutional support: RVO:67985823 Keywords : hippocampus * long-term potentiation * membrane proteins Subject RIV: FH - Neurology OBOR OECD: Neuroscience s (including psychophysiology Impact factor: 17.839, year: 2016

  16. Virtual Burglary: Exploring the Potential of Virtual Reality to Study Burglary in Action

    NARCIS (Netherlands)

    van Sintemaartensdijk, I.; van Prooijen, J-W.; van Gelder, J-L.; Otte, M.; Nee, Claire; Demetriou, Andrew

    2016-01-01

    Objectives: This article explores the potential of virtual reality (VR) to study burglary by measuring user responses on the subjective, physiological, and behavioral levels. Furthermore, it examines the influence of individual dispositions, such as sensation seeking and self-control, on behavior

  17. Monoamine Oxidase-A Inhibition and Associated Antioxidant Activity in Plant Extracts with Potential Antidepressant Actions

    Directory of Open Access Journals (Sweden)

    Tomás Herraiz

    2018-01-01

    Full Text Available Monoamine oxidase (MAO catalyzes the oxidative deamination of amines and neurotransmitters and is involved in mood disorders, depression, oxidative stress, and adverse pharmacological reactions. This work studies the inhibition of human MAO-A by Hypericum perforatum, Peganum harmala, and Lepidium meyenii, which are reported to improve and affect mood and mental conditions. Subsequently, the antioxidant activity associated with the inhibition of MAO is determined in plant extracts for the first time. H. perforatum inhibited human MAO-A, and extracts from flowers gave the highest inhibition (IC50 of 63.6 μg/mL. Plant extracts were analyzed by HPLC-DAD-MS and contained pseudohypericin, hypericin, hyperforin, adhyperforin, hyperfirin, and flavonoids. Hyperforin did not inhibit human MAO-A and hypericin was a poor inhibitor of this isoenzyme. Quercetin and flavonoids significantly contributed to MAO-A inhibition. P. harmala seed extracts highly inhibited MAO-A (IC50 of 49.9 μg/L, being a thousand times more potent than H. perforatum extracts owing to its content of β-carboline alkaloids (harmaline and harmine. L. meyenii root (maca extracts did not inhibit MAO-A. These plants may exert protective actions related to antioxidant effects. Results in this work show that P. harmala and H. perforatum extracts exhibit antioxidant activity associated with the inhibition of MAO (i.e., lower production of H2O2.

  18. 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.

  19. Barriers, facilitators, and potential strategies for increasing HPV vaccination: A statewide assessment to inform action

    Directory of Open Access Journals (Sweden)

    Kathleen B. Cartmell

    2018-06-01

    Full Text Available Objective: The objective was to investigate how state level strategies in South Carolina could maximize HPV vaccine uptake. Design: An environmental scan identified barriers, facilitators, and strategies for improving HPV vaccination in South Carolina. Interviews were conducted with state leaders from relevant organizations such as public health agencies, medical associations, K-12 schools, universities, insurers, and cancer advocacy organizations. A thematic content analysis design was used. Digital interview files were transcribed, a data dictionary was created and data were coded using the data dictionary. Results: Thirty four interviews were conducted with state leaders. Barriers to HPV vaccination included lack of HPV awareness, lack of provider recommendation, HPV vaccine concerns, lack of access and practice-level barriers. Facilitators included momentum for improving HPV vaccination, school-entry Tdap requirement, pharmacy-based HPV vaccination, state immunization registry, HEDIS measures and HPV vaccine funding. Strategies for improving HPV vaccination fell into three categories: 1 addressing lack of awareness about the importance of HPV vaccination among the public and providers; 2 advocating for policy changes around HPV vaccine coverage, vaccine education, and pharmacy-based vaccination; and 3 coordination of efforts. Discussion: A statewide environmental scan generated a blueprint for action to be used to improve HPV vaccination in the state. Keywords: HPV, HPV vaccines, Cervical cancer, Prevention, Health systems, Barriers, Facilitators, Strategies, South Carolina

  20. Novel experimental results in human cardiac electrophysiology: measurement of the Purkinje fibre action potential from the undiseased human heart.

    Science.gov (United States)

    Nagy, Norbert; Szél, Tamás; Jost, Norbert; Tóth, András; Gy Papp, Julius; Varró, András

    2015-09-01

    Data obtained from canine cardiac electrophysiology studies are often extrapolated to the human heart. However, it has been previously demonstrated that because of the lower density of its K(+) currents, the human ventricular action potential has a less extensive repolarization reserve. Since the relevance of canine data to the human heart has not yet been fully clarified, the aim of the present study was to determine for the first time the action potentials of undiseased human Purkinje fibres (PFs) and to compare them directly with those of dog PFs. All measurements were performed at 37 °C using the conventional microelectrode technique. At a stimulation rate of 1 Hz, the plateau potential of human PFs is more positive (8.0 ± 1.8 vs 8.6 ± 3.4 mV, n = 7), while the amplitude of the spike is less pronounced. The maximal rate of depolarization is significantly lower in human PKs than in canine PFs (406.7 ± 62 vs 643 ± 36 V/s, respectively, n = 7). We assume that the appreciable difference in the protein expression profiles of the 2 species may underlie these important disparities. Therefore, caution is advised when canine PF data are extrapolated to humans, and further experiments are required to investigate the characteristics of human PF repolarization and its possible role in arrhythmogenesis.

  1. Loss of Local Astrocyte Support Disrupts Action Potential Propagation and Glutamate Release Synchrony from Unmyelinated Hippocampal Axon Terminals In Vitro.

    Science.gov (United States)

    Sobieski, Courtney; Jiang, Xiaoping; Crawford, Devon C; Mennerick, Steven

    2015-08-05

    Neuron-astrocyte interactions are critical for proper CNS development and function. Astrocytes secrete factors that are pivotal for synaptic development and function, neuronal metabolism, and neuronal survival. Our understanding of this relationship, however, remains incomplete due to technical hurdles that have prevented the removal of astrocytes from neuronal circuits without changing other important conditions. Here we overcame this obstacle by growing solitary rat hippocampal neurons on microcultures that were comprised of either an astrocyte bed (+astrocyte) or a collagen bed (-astrocyte) within the same culture dish. -Astrocyte autaptic evoked EPSCs, but not IPSCs, displayed an altered temporal profile, which included increased synaptic delay, increased time to peak, and severe glutamate release asynchrony, distinct from previously described quantal asynchrony. Although we observed minimal alteration of the somatically recorded action potential waveform, action potential propagation was altered. We observed a longer latency between somatic initiation and arrival at distal locations, which likely explains asynchronous EPSC peaks, and we observed broadening of the axonal spike, which likely underlies changes to evoked EPSC onset. No apparent changes in axon structure were observed, suggesting altered axonal excitability. In conclusion, we propose that local astrocyte support has an unappreciated role in maintaining glutamate release synchrony by disturbing axonal signal propagation. Certain glial cell types (oligodendrocytes, Schwann cells) facilitate the propagation of neuronal electrical signals, but a role for astrocytes has not been identified despite many other functions of astrocytes in supporting and modulating neuronal signaling. Under identical global conditions, we cultured neurons with or without local astrocyte support. Without local astrocytes, glutamate transmission was desynchronized by an alteration of the waveform and arrival time of axonal

  2. Directed fusion of cardiac spheroids into larger heterocellular microtissues enables investigation of cardiac action potential propagation via cardiac fibroblasts

    Science.gov (United States)

    Markes, Alexander R.; Okundaye, Amenawon O.; Qu, Zhilin; Mende, Ulrike; Choi, Bum-Rak

    2018-01-01

    Multicellular spheroids generated through cellular self-assembly provide cytoarchitectural complexities of native tissue including three-dimensionality, extensive cell-cell contacts, and appropriate cell-extracellular matrix interactions. They are increasingly suggested as building blocks for larger engineered tissues to achieve shapes, organization, heterogeneity, and other biomimetic complexities. Application of these tissue culture platforms is of particular importance in cardiac research as the myocardium is comprised of distinct but intermingled cell types. Here, we generated scaffold-free 3D cardiac microtissue spheroids comprised of cardiac myocytes (CMs) and/or cardiac fibroblasts (CFs) and used them as building blocks to form larger microtissues with different spatial distributions of CMs and CFs. Characterization of fusing homotypic and heterotypic spheroid pairs revealed an important influence of CFs on fusion kinetics, but most strikingly showed rapid fusion kinetics between heterotypic pairs consisting of one CF and one CM spheroid, indicating that CMs and CFs self-sort in vitro into the intermixed morphology found in the healthy myocardium. We then examined electrophysiological integration of fused homotypic and heterotypic microtissues by mapping action potential propagation. Heterocellular elongated microtissues which recapitulate the disproportionate CF spatial distribution seen in the infarcted myocardium showed that action potentials propagate through CF volumes albeit with significant delay. Complementary computational modeling revealed an important role of CF sodium currents and the spatial distribution of the CM-CF boundary in action potential conduction through CF volumes. Taken together, this study provides useful insights for the development of complex, heterocellular engineered 3D tissue constructs and their engraftment via tissue fusion and has implications for arrhythmogenesis in cardiac disease and repair. PMID:29715271

  3. Directed fusion of cardiac spheroids into larger heterocellular microtissues enables investigation of cardiac action potential propagation via cardiac fibroblasts.

    Directory of Open Access Journals (Sweden)

    Tae Yun Kim

    Full Text Available Multicellular spheroids generated through cellular self-assembly provide cytoarchitectural complexities of native tissue including three-dimensionality, extensive cell-cell contacts, and appropriate cell-extracellular matrix interactions. They are increasingly suggested as building blocks for larger engineered tissues to achieve shapes, organization, heterogeneity, and other biomimetic complexities. Application of these tissue culture platforms is of particular importance in cardiac research as the myocardium is comprised of distinct but intermingled cell types. Here, we generated scaffold-free 3D cardiac microtissue spheroids comprised of cardiac myocytes (CMs and/or cardiac fibroblasts (CFs and used them as building blocks to form larger microtissues with different spatial distributions of CMs and CFs. Characterization of fusing homotypic and heterotypic spheroid pairs revealed an important influence of CFs on fusion kinetics, but most strikingly showed rapid fusion kinetics between heterotypic pairs consisting of one CF and one CM spheroid, indicating that CMs and CFs self-sort in vitro into the intermixed morphology found in the healthy myocardium. We then examined electrophysiological integration of fused homotypic and heterotypic microtissues by mapping action potential propagation. Heterocellular elongated microtissues which recapitulate the disproportionate CF spatial distribution seen in the infarcted myocardium showed that action potentials propagate through CF volumes albeit with significant delay. Complementary computational modeling revealed an important role of CF sodium currents and the spatial distribution of the CM-CF boundary in action potential conduction through CF volumes. Taken together, this study provides useful insights for the development of complex, heterocellular engineered 3D tissue constructs and their engraftment via tissue fusion and has implications for arrhythmogenesis in cardiac disease and repair.

  4. A code to compute the action-angle transformation for a particle in an abritrary potential well

    International Nuclear Information System (INIS)

    Berg, J.S.; Warnock, R.L.

    1995-01-01

    For a Vlasov treatment of longitudinal stability under an arbitrary wake field, with the solution of the Haiessinski equation as the unperturbed distribution, it is important to have the action-angle transformation for the distorted potential well in a convenient form. The authors have written a code that gives the transformation q,p → J, φ, with q(J,φ) as a Fourier series in φ, the Fourier coefficients and the Hamiltonian H(J) being spline functions of J in C 2 (having continuous second derivatives)

  5. Potential need for re-definition of the highest priority recovery action in the Krsko SAG-1

    International Nuclear Information System (INIS)

    Bilic Zabric, T.; Basic, I.

    2005-01-01

    Replacement of old SG (Steam Generators) [7] and the characteristic of new ones throws the question of proper accident management strategy, which leans on philosophy that repair and recovery actions have first priority. In the current NPP Krsko SAMGs (Severe Accident Management Guidelines), water supply to the SG has priority over re-injection water into the core. NPP Krsko reconsidered the highest priority of SAG-1 (inject water to the SG), against the WOG (Westinghouse Owners Group) generic approach (inject water into the core) and potential revision of Severe Accident Phenomenology Evaluations using MAAP (Modular accident Analysis Program) 4.0.5 code. (author)

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

    DEFF Research Database (Denmark)

    Liu, Xiaowen; Murali, Sangita G; Holst, Jens J

    2009-01-01

    protein component, casein, soy, or whey protein, potentiates the intestinal growth response to GLP-2 in rats with PN-induced mucosal hypoplasia. Rats received PN and continuous intravenous infusion of GLP-2 (100 microg/kg/day) for 7 days. Six EN groups received PN+GLP-2 for days 1-3 and partial PN+GLP-2...... plus EN for days 4-7. EN was provided by ad libitum intake of a semielemental liquid diet with different protein sources: casein, hydrolyzed soy, whey protein concentrate (WPC), and hydrolyzed WPC+casein. Controls received PN+GLP-2 alone. EN induced significantly greater jejunal sucrase activity...... whey protein, and not casein or soy, potentiated the ability of GLP-2 to reverse PN-induced mucosal hypoplasia and further increase ileal villus height, crypt depth, and mucosa cellularity compared with PN+GLP-2 alone, P whey protein to induce greater mucosal surface area...

  7. Navy Ship Maintenance: Action Needed to Maximize New Contracting Strategys Potential Benefits

    Science.gov (United States)

    2016-11-01

    implementation of the new strategy, the Navy conducted market research and pilot-tested attributes of the strategy with pilot maintenance periods for a...readiness strategy and, in 2015, introduction of a new contracting strategy for ship repair, referred to as MAC-MO. House Report 114-102 accompanying the...Maintenance Letter 1 Background 3 Market Research and Piloting Helped Inform Roll-out of MAC-MO Strategy, Which Offers Potential Benefits

  8. Exact effective action for (1+1)-dimensional fermions in an Abelian background at finite temperature and chemical potential

    International Nuclear Information System (INIS)

    Maciel, Soraya G.; Perez, Silvana

    2008-01-01

    In this paper we study the effects of a nonzero chemical potential in (1+1)-dimensional quantum field models at finite temperature. We particularly consider massless fermions in an Abelian gauge field background and calculate the effective action by evaluating the n-point functions. We find that the structure of the amplitudes corresponds to a generalization of the structure noted earlier in a calculation without a chemical potential (the associated integrals carry the dependence on the chemical potential). Our calculation shows that the chiral anomaly is unaffected by the presence of a chemical potential at finite temperature. However, unlike in the absence of a chemical potential, odd point functions do not vanish. We trace this to the fact that in the presence of a chemical potential the generalized charge conjugation symmetry of the theory allows for such amplitudes. In fact, we find that all the even point functions are even functions of μ, while the odd point functions are odd functions of μ which is consistent with this generalized charge conjugation symmetry. We show that the origin of the structure of the amplitudes is best seen from a formulation of the theory in terms of left- and right-handed spinors. The calculations are also much simpler in this formulation and it clarifies many other aspects of the theory.

  9. Four- year thyroidectomy procedures: Ligasure Vs. clamp & tie

    Directory of Open Access Journals (Sweden)

    Pazoki AR

    2010-01-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: The electrothermal bipolar vessel sealing system is an adjunct to the hemostatic technique, which has been successfully used in many abdominal operation, recently made available to thyroid surgery. The purpose of this was compare the outcomes of new hemostatic technique with traditional method of clamp and tie."n"nMethods: In this retrospective cross-sectional study has been done in surgery's wards of Milad & Rasul- Akram hospitals in Tehran, Iran. During three- year period between 2005-2008 all patients with different kind of pathology that need operation were assessed. Time duration of surgery and hospital stay and post surgery complication in two group, ligasure (n=45 and clamp & tie (n=145 were compared with each others."n"nResults: No difference was seen between two groups in time duration of surgery. Significant difference was seen in hospital stay and complications of surgery. Time of operation in Ligasure group was 132/22 minute and in clamp and tie group was 130/10 minute. There was found significant difference in duration of hospital stay and postoperative complication. Hypocalcemia were seen in two and 24 cases in Ligasure and Clamp & Tie group, respectively (p<0.05. Hospital stay was 2

  10. The potential role of cotinine in the cognitive and neuroprotective actions of nicotine.

    Science.gov (United States)

    Buccafusco, Jerry J; Terry, Alvin V

    2003-05-16

    Cotinine is a primary metabolite of nicotine that has been suggested in many studies in animals and in humans to exert measurable effects on aspects of on-going behavior or on cognitive function. Much of the interest in cotinine derives from its long pharmacological half-life (15-19 hours) relative to nicotine (2-3 hours). Despite decades of study focusing on nicotine as the predominant behaviorally active component of tobacco, there continue to be aspects of the pharmacology of the drug that have yet to be explained. For example, nicotine can evoke a protracted behavioral response, i.e., in great excess of the presence of the drug in the plasma. Also, there is often a striking differential between the potency for nicotine-induced behavioral responses in humans and animals, and its potency as a cholinergic agonist, neurochemically. One possibility that may explain one or more of these properties of nicotine is the presence of a long-lived bioactive metabolite or breakdown product of nicotine such as cotinine. Preliminary data in support of this hypothesis are consistent with the ability of cotinine to improve performance accuracy on delayed matching task by macaque monkeys, and in reversing apomorphine-induced deficits in prepulse inhibition of acoustic startle in rats. The drug also was shown to be as potent as nicotine in the ability to act as a cytoprotective agent in cells that express a neuronal cholinergic phenotype. This new appreciation for the role of cotinine in nicotine's actions, and as a pharmacological agent in its own right, particularly in aspects of cognitive function and for neuroprotection, ultimately may be applied towards the treatment of Alzheimer's disease and related disorders, and for various psychiatric syndromes.

  11. Ameliorating treatment-refractory depression with intranasal ketamine: potential NMDA receptor actions in the pain circuitry representing mental anguish.

    Science.gov (United States)

    Opler, Lewis A; Opler, Mark G A; Arnsten, Amy F T

    2016-02-01

    This article reviews the antidepressant actions of ketamine, an N-methyl-D-aspartame glutamate receptor (NMDAR) antagonist, and offers a potential neural mechanism for intranasal ketamine's ultra-rapid actions based on the key role of NMDAR in the nonhuman primate prefrontal cortex (PFC). Although intravenous ketamine infusions can lift mood within hours, the current review describes how intranasal ketamine administration can have ultra-rapid antidepressant effects, beginning within minutes (5-40 minutes) and lasting hours, but with repeated treatments needed for sustained antidepressant actions. Research in rodents suggests that increased synaptogenesis in PFC may contribute to the prolonged benefit of ketamine administration, beginning hours after administration. However, these data cannot explain the relief that occurs within minutes of intranasal ketamine delivery. We hypothesize that the ultra-rapid effects of intranasal administration in humans may be due to ketamine blocking the NMDAR circuits that generate the emotional representations of pain (eg, Brodmann Areas 24 and 25, insular cortex), cortical areas that can be overactive in depression and which sit above the nasal epithelium. In contrast, NMDAR blockade in the dorsolateral PFC following systemic administration of ketamine may contribute to cognitive deficits. This novel view may help to explain how intravenous ketamine can treat the symptoms of depression yet worsen the symptoms of schizophrenia.

  12. AMELIORATING TREATMENT-REFRACTORY DEPRESSION WITH INTRANASAL KETAMINE: POTENTIAL NMDA RECEPTOR ACTIONS IN THE PAIN CIRCUITRY REPRESENTING MENTAL ANGUISH

    Science.gov (United States)

    Opler, Lewis A.; Opler, Mark G.; Arnsten, Amy F.T.

    2014-01-01

    This paper reviews the anti-depressant actions of the N-methyl-D-aspartame glutamate receptor (NMDAR) antagonist, ketamine, and offers a potential neural mechanism for intranasal ketamine’s ultra-rapid actions based on the key role of NMDAR in the nonhuman primate prefrontal cortex (PFC). Although intravenous ketamine infusions can lift mood within hours, the current review describes how intranasal ketamine administration can have ultra-rapid antidepressant effects, beginning within minutes (5–40 minutes) and lasting hours, but with repeated treatments needed for sustained antidepressant actions. Research in rodents suggests that increased synaptogenesis in PFC may contribute to the prolonged benefit of ketamine administration, beginning hours after administration. However, these data cannot explain the relief that occurs within minutes of intranasal ketamine delivery. We hypothesize that the ultra-rapid effects of intranasal administration in humans may be due to ketamine blocking the NMDAR circuits that generate the emotional representations of pain (e.g. Brodmann Areas 24 and 25, insular cortex), cortical areas that can be overactive in depression and which sit above the nasal epithelium. In contrast, NMDAR blockade in the dorsolateral PFC following systemic administration of ketamine may contribute to cognitive deficits. This novel view may help to explain how intravenous ketamine can treat the symptoms of depression yet worsen the symptoms of schizophrenia. PMID:25619798

  13. 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.

  14. Higher order modes excitation of electrostatically actuated clamped–clamped microbeams: experimental and analytical investigation

    KAUST Repository

    Jaber, Nizar; Ramini, Abdallah; Carreno, Armando Arpys Arevalo; Younis, Mohammad I.

    2016-01-01

    © 2016 IOP Publishing Ltd. In this study, we demonstrate analytically and experimentally the excitations of the higher order modes of vibrations in electrostatically actuated clamped-clamped microbeam resonators. The concept is based on using

  15. Active energy recovery clamping circuit to improve the performance of power converters

    Science.gov (United States)

    Whitaker, Bret; Barkley, Adam

    2017-05-09

    A regenerative clamping circuit for a power converter using clamping diodes to transfer charge to a clamping capacitor and a regenerative converter to transfer charge out of the clamping capacitor back to the power supply input connection. The regenerative converter uses a switch connected to the midpoint of a series connected inductor and capacitor. The ends of the inductor and capacitor series are connected across the terminals of the power supply to be in parallel with the power supply.

  16. In situ vitrification - A potential remedial action technique for hazardous wastes

    International Nuclear Information System (INIS)

    Fitzpatrick, V.F.; Buelt, J.L.; Oma, K.H.; Timmerman, C.L.

    1984-01-01

    In situ vitrification (ISV) is an innovative technology being developed as a potential method for stabilizing transuranic (TRU) contaminated wastes in place. Although the process is being developed for TRU contaminated wastes, it is envisioned that the process could also be applied to hazardous chemical wastes. In situ vitrification (ISV) is the conversion of contaminated soil into a durable glass and crystalline wastes form through melting by joule heating. The technology for in situ vitrification is based upon electric melter technology developed at the Pacific Northwest Laboratory (PNL) for the immobilization of high-level nuclear waste. In situ vitrification was initially tested by researchers at PNL in August, 1980 (U.S. Patent 4,376,598). Since then, ISV has grown from a concept to an emerging technology through a series of 21 engineering-scale (laboratory) tests and 7 pilot-scale (field) tests. A large-scale system is currently being fabricated for testing. The program has been sponsored by the U.S. Department of Energy's (DOE) Richland Operations Office for potential application to Hanford TRU contaminated soil sites. A more detailed description outlining the power system design and the off-gas treatment system follows

  17. The energy cost of action potential propagation in dopamine neurons: clues to susceptibility in Parkinson's disease.

    Science.gov (United States)

    Pissadaki, Eleftheria K; Bolam, J Paul

    2013-01-01

    Dopamine neurons of the substantia nigra pars compacta (SNc) are uniquely sensitive to degeneration in Parkinson's disease (PD) and its models. Although a variety of molecular characteristics have been proposed to underlie this sensitivity, one possible contributory factor is their massive, unmyelinated axonal arbor that is orders of magnitude larger than other neuronal types. We suggest that this puts them under such a high energy demand that any stressor that perturbs energy production leads to energy demand exceeding supply and subsequent cell death. One prediction of this hypothesis is that those dopamine neurons that are selectively vulnerable in PD will have a higher energy cost than those that are less vulnerable. We show here, through the use of a biology-based computational model of the axons of individual dopamine neurons, that the energy cost of axon potential propagation and recovery of the membrane potential increases with the size and complexity of the axonal arbor according to a power law. Thus SNc dopamine neurons, particularly in humans, whose axons we estimate to give rise to more than 1 million synapses and have a total length exceeding 4 m, are at a distinct disadvantage with respect to energy balance which may be a factor in their selective vulnerability in PD.

  18. An evaluation of the utility and limitations of counting motor unit action potentials in the surface electromyogram

    Science.gov (United States)

    Zhou, Ping; Zev Rymer, William

    2004-12-01

    The number of motor unit action potentials (MUAPs) appearing in the surface electromyogram (EMG) signal is directly related to motor unit recruitment and firing rates and therefore offers potentially valuable information about the level of activation of the motoneuron pool. In this paper, based on morphological features of the surface MUAPs, we try to estimate the number of MUAPs present in the surface EMG by counting the negative peaks in the signal. Several signal processing procedures are applied to the surface EMG to facilitate this peak counting process. The MUAP number estimation performance by this approach is first illustrated using the surface EMG simulations. Then, by evaluating the peak counting results from the EMG records detected by a very selective surface electrode, at different contraction levels of the first dorsal interosseous (FDI) muscles, the utility and limitations of such direct peak counts for MUAP number estimation in surface EMG are further explored.

  19. Gigaseal formation in patch clamping with applications of nanotechnology

    CERN Document Server

    Malboubi, Majid

    2014-01-01

    This book presents an investigation of gigaseal formation using micro/nanotechnology. The aims of the book are twofold. First, it explains the mechanisms of gigaseal formation using the latest discoveries. Second, it provides practical techniques for frequent formation of high resistance seals. The formation of a high-resistance electrical seal, also known as a gigaseal, between a cell membrane and a glass micropipette tip is essential in patch-clamp experiments. Even though four decades have passed since the introduction of the patch-clamping technique by Neher and Sakmann, gigaseal formation remains an obstacle in developing the high-throughput ion channel screening systems required by the pharmaceutical industry. Here the authors share their latest methods for achieving gigaseal formation and describe techniques that are highly desirable at both research and industrial levels. Nanotechnology has been found to be a powerful tool for studying and modifying glass micropipettes and in tackling the problem of g...

  20. Intraoperative observation of changes in cochlear nerve action potentials during exposure to electromagnetic fields generated by mobile phones.

    Science.gov (United States)

    Colletti, Vittorio; Mandalà, Marco; Manganotti, Paolo; Ramat, Stefano; Sacchetto, Luca; Colletti, Liliana

    2011-07-01

    The rapid spread of devices generating electromagnetic fields (EMF) has raised concerns as to the possible effects of this technology on humans. The auditory system is the neural organ most frequently and directly exposed to electromagnetic activity owing to the daily use of mobile phones. In recent publications, a possible correlation between mobile phone usage and central nervous system tumours has been detected. Very recently a deterioration in otoacoustic emissions and in the auditory middle latency responses after intensive and long-term magnetic field exposure in humans has been demonstrated. To determine with objective observations if exposure to mobile phone EMF affects acoustically evoked cochlear nerve compound action potentials, seven patients suffering from Ménière's disease and undergoing retrosigmoid vestibular neurectomy were exposed to the effects of mobile phone placed over the craniotomy for 5 min. All patients showed a substantial decrease in amplitude and a significant increase in latency of cochlear nerve compound action potentials during the 5 min of exposure to EMF. These changes lasted for a period of around 5 min after exposure. The possibility that EMF can produce relatively long-lasting effects on cochlear nerve conduction is discussed and analysed in light of contrasting previous literature obtained under non-surgical conditions. Limitations of this novel approach, including the effects of the anaesthetics, craniotomy and surgical procedure, are presented in detail.

  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. Period doubling cascades of limit cycles in cardiac action potential models as precursors to chaotic early Afterdepolarizations.

    Science.gov (United States)

    Kügler, Philipp; Bulelzai, M A K; Erhardt, André H

    2017-04-04

    Early afterdepolarizations (EADs) are pathological voltage oscillations during the repolarization phase of cardiac action potentials (APs). EADs are caused by drugs, oxidative stress or ion channel disease, and they are considered as potential precursors to cardiac arrhythmias in recent attempts to redefine the cardiac drug safety paradigm. The irregular behaviour of EADs observed in experiments has been previously attributed to chaotic EAD dynamics under periodic pacing, made possible by a homoclinic bifurcation in the fast subsystem of the deterministic AP system of differential equations. In this article we demonstrate that a homoclinic bifurcation in the fast subsystem of the action potential model is neither a necessary nor a sufficient condition for the genesis of chaotic EADs. We rather argue that a cascade of period doubling (PD) bifurcations of limit cycles in the full AP system paves the way to chaotic EAD dynamics across a variety of models including a) periodically paced and spontaneously active cardiomyocytes, b) periodically paced and non-active cardiomyocytes as well as c) unpaced and spontaneously active cardiomyocytes. Furthermore, our bifurcation analysis reveals that chaotic EAD dynamics may coexist in a stable manner with fully regular AP dynamics, where only the initial conditions decide which type of dynamics is displayed. EADs are a potential source of cardiac arrhythmias and hence are of relevance both from the viewpoint of drug cardiotoxicity testing and the treatment of cardiomyopathies. The model-independent association of chaotic EADs with period doubling cascades of limit cycles introduced in this article opens novel opportunities to study chaotic EADs by means of bifurcation control theory and inverse bifurcation analysis. Furthermore, our results may shed new light on the synchronization and propagation of chaotic EADs in homogeneous and heterogeneous multicellular and cardiac tissue preparations.

  3. Exploring potential mechanisms of action of natalizumab in secondary progressive multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, Finn; Cadavid, Diego; Steiner, Deborah

    2016-01-01

    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......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......, 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...

  4. 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...

  5. Analysis of whole-cell currents by patch clamp of guinea-pig myenteric neurones in intact ganglia

    Science.gov (United States)

    Rugiero, François; Gola, Maurice; Kunze, Wolf A A; Reynaud, Jean-Claude; Furness, John B; Clerc, Nadine

    2002-01-01

    Whole-cell patch-clamp recordings taken from guinea-pig duodenal myenteric neurones within intact ganglia were used to determine the properties of S and AH neurones. Major currents that determine the states of AH neurones were identified and quantified. S neurones had resting potentials of −47 ± 6 mV and input resistances (Rin) of 713 ± 49 MΩ at voltages ranging from −90 to −40 mV. At more negative levels, activation of a time-independent, caesium-sensitive, inward-rectifier current (IKir) decreased Rin to 103 ± 10 MΩ. AH neurones had resting potentials of −57 ± 4 mV and Rin was 502 ± 27 MΩ. Rin fell to 194 ± 16 MΩ upon hyperpolarization. This decrease was attributable mainly to the activation of a cationic h current, Ih, and to IKir. Resting potential and Rin exhibited a low sensitivity to changes in [K+]o in both AH and S neurones. This indicates that both cells have a low background K+ permeability. The cationic current, Ih, contributed about 20 % to the resting conductance of AH neurones. It had a half-activation voltage of −72 ± 2 mV, and a voltage sensitivity of 8.2 ± 0.7 mV per e-fold change. Ih has relatively fast, voltage-dependent kinetics, with on and off time constants in the range of 50–350 ms. AH neurones had a previously undescribed, low threshold, slowly inactivating, sodium-dependent current that was poorly sensitive to TTX. In AH neurones, the post-action-potential slow hyperpolarizing current, IAHP, displayed large variation from cell to cell. IAHP appeared to be highly Ca2+ sensitive, since its activation with either membrane depolarization or caffeine (1 mm) was not prevented by perfusing the cell with 10 mm BAPTA. We determined the identity of the Ca2+ channels linked to IAHP. Action potentials of AH neurones that were elongated by TEA (10 mm) were similarly shortened and IAHP was suppressed with each of the three Ω-conotoxins GVIA, MVIIA and MVIIC (0.3–0.5 μm), but not with Ω-agatoxin IVA (0.2 μm). There was no

  6. Analyzing the greenhouse gas impact potential of smallholder development actions across a global food security program

    Science.gov (United States)

    Grewer, Uwe; Nash, Julie; Gurwick, Noel; Bockel, Louis; Galford, Gillian; Richards, Meryl; Costa Junior, Ciniro; White, Julianna; Pirolli, Gillian; Wollenberg, Eva

    2018-04-01

    This article analyses the greenhouse gas (GHG) impact potential of improved management practices and technologies for smallholder agriculture promoted under a global food security development program. Under ‘business-as-usual’ development, global studies on the future of agriculture to 2050 project considerable increases in total food production and cultivated area. Conventional cropland intensification and conversion of natural vegetation typically result in increased GHG emissions and loss of carbon stocks. There is a strong need to understand the potential greenhouse gas impacts of agricultural development programs intended to achieve large-scale change, and to identify pathways of smallholder agricultural development that can achieve food security and agricultural production growth without drastic increases in GHG emissions. In an analysis of 134 crop and livestock production systems in 15 countries with reported impacts on 4.8 million ha, improved management practices and technologies by smallholder farmers significantly reduce GHG emission intensity of agricultural production, increase yields and reduce post-harvest losses, while either decreasing or only moderately increasing net GHG emissions per area. Investments in both production and post-harvest stages meaningfully reduced GHG emission intensity, contributing to low emission development. We present average impacts on net GHG emissions per hectare and GHG emission intensity, while not providing detailed statistics of GHG impacts at scale that are associated to additional uncertainties. While reported improvements in smallholder systems effectively reduce future GHG emissions compared to business-as-usual development, these contributions are insufficient to significantly reduce net GHG emission in agriculture beyond current levels, particularly if future agricultural production grows at projected rates.

  7. Dipeptidyl peptidase IV as a potential target for selective prodrug activation and chemotherapeutic action in cancers.

    Science.gov (United States)

    Dahan, Arik; Wolk, Omri; Yang, Peihua; Mittal, Sachin; Wu, Zhiqian; Landowski, Christopher P; Amidon, Gordon L

    2014-12-01

    The efficacy of chemotherapeutic drugs is often offset by severe side effects attributable to poor selectivity and toxicity to normal cells. Recently, the enzyme dipeptidyl peptidase IV (DPPIV) was considered as a potential target for the delivery of chemotherapeutic drugs. The purpose of this study was to investigate the feasibility of targeting chemotherapeutic drugs to DPPIV as a strategy to enhance their specificity. The expression profile of DPPIV was obtained for seven cancer cell lines using DNA microarray data from the DTP database, and was validated by RT-PCR. A prodrug was then synthesized by linking the cytotoxic drug melphalan to a proline-glycine dipeptide moiety, followed by hydrolysis studies in the seven cell lines with a standard substrate, as well as the glycyl-prolyl-melphalan (GP-Mel). Lastly, cell proliferation studies were carried out to demonstrate enzyme-dependent activation of the candidate prodrug. The relative RT-PCR expression levels of DPPIV in the cancer cell lines exhibited linear correlation with U95Av2 Affymetrix data (r(2) = 0.94), and with specific activity of a standard substrate, glycine-proline-p-nitroanilide (r(2) = 0.96). The significantly higher antiproliferative activity of GP-Mel in Caco-2 cells (GI₅₀ = 261 μM) compared to that in SK-MEL-5 cells (GI₅₀ = 807 μM) was consistent with the 9-fold higher specific activity of the prodrug in Caco-2 cells (5.14 pmol/min/μg protein) compared to SK-MEL-5 cells (0.68 pmol/min/μg protein) and with DPPIV expression levels in these cells. Our results demonstrate the great potential to exploit DPPIV as a prodrug activating enzyme for efficient chemotherapeutic drug targeting.

  8. Analysis of the Pallet Clamping Conditions in Work Positioning

    OpenAIRE

    L. A. Kolesnikov

    2016-01-01

    Pallets of automatic transfer lines serve as the technological and work-transfer equipment. However, their design is based on the general principles of designing machine accessories. Calculation of the basic design parameters of work based on their functioning features is fairly relevant.In pallet transfer movement over work positioning there is a mismatch between axes of the basic bushing of a pallet and the clamping locks of positioning. The paper identifies the factors influencing it, and ...

  9. Constant-frequency, clamped-mode resonant converters

    Science.gov (United States)

    Tsai, Fu-Sheng; Materu, Peter; Lee, Fred C.

    1987-01-01

    Two novel clamped-mode resonant converters are proposed which operate at a constant frequency while retaining many desired features of conventional series- and parallel-resonant converters. State-plane analysis techniques are used to identify all possible operating modes and define their mode boundaries. Control-to-output characteristics are derived that specify the regions for natural and forced commutation. The predicted operating modes are verified using a prototype circuit.

  10. Voltage Balancing Control of Diode-Clamped Multilevel Inverter

    Directory of Open Access Journals (Sweden)

    ŞCHIOP Adrian

    2013-10-01

    Full Text Available In this paper is developed a control scheme for mono-phase diode clamped inverter to achieve balancing voltages on inverter capacitors. First, it develops a control scheme without taking into account the need to balance voltage on two capacitors. It examines the effects on the output voltage inverter, and then it realizes two control schemes that will balance the voltages. The simulations of control schemes were performed in OrCAD Pspice.

  11. File list: Oth.ALL.50.Clamp.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.ALL.50.Clamp.AllCell dm3 TFs and others Clamp All cell types SRX159172,SRX15917...0,SRX159174,SRX159166,SRX159173 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/Oth.ALL.50.Clamp.AllCell.bed ...

  12. File list: Oth.CeL.50.Clamp.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.CeL.50.Clamp.AllCell dm3 TFs and others Clamp Cell line SRX159172,SRX159170,SRX...159174,SRX159166,SRX159173 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/Oth.CeL.50.Clamp.AllCell.bed ...

  13. File list: Oth.CeL.05.Clamp.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.CeL.05.Clamp.AllCell dm3 TFs and others Clamp Cell line SRX159172,SRX159170,SRX...159174,SRX159166,SRX159173 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/Oth.CeL.05.Clamp.AllCell.bed ...

  14. Role of the Checkpoint Clamp in DNA Damage Response

    Directory of Open Access Journals (Sweden)

    Mihoko Kai

    2013-01-01

    Full Text Available DNA damage occurs during DNA replication, spontaneous chemical reactions, and assaults by external or metabolism-derived agents. Therefore, all living cells must constantly contend with DNA damage. Cells protect themselves from these genotoxic stresses by activating the DNA damage checkpoint and DNA repair pathways. Coordination of these pathways requires tight regulation in order to prevent genomic instability. The checkpoint clamp complex consists of Rad9, Rad1 and Hus1 proteins, and is often called the 9-1-1 complex. This PCNA (proliferating cell nuclear antigen-like donut-shaped protein complex is a checkpoint sensor protein that is recruited to DNA damage sites during the early stage of the response, and is required for checkpoint activation. As PCNA is required for multiple pathways of DNA metabolism, the checkpoint clamp has also been implicated in direct roles in DNA repair, as well as in coordination of the pathways. Here we discuss roles of the checkpoint clamp in DNA damage response (DDR.

  15. Current Government Actions and Potential Policy Options for Reducing Obesity in Queensland Schools

    Directory of Open Access Journals (Sweden)

    Naser A. Alsharairi

    2018-01-01

    Full Text Available School nutrition policies provide promising avenues towards the improvement of children’s eating habits and the prevention of obesity. Childhood obesity rates and related chronic diseases are increasing in Queensland, in part as a result of unhealthy eating habits and lack of physical activity. There is a very high investment by the Queensland government in maintaining healthy weight and promoting nutrition and physical activity among schoolchildren through delivering a range of initiatives across the state. However, there is a lack of evidence concerning the effectiveness of nutrition/physical education and parental involvement programs addressing obesity delivered in Queensland schools. This paper can be used to guide government and policy-makers regarding the most effective policy options that will promote healthy eating and physical activity among Queensland schoolchildren. The aim of this paper is to: (i summarize current evidence on Queensland government responses to obesity; and (ii discuss potential policy options that could support healthy eating and regular physical activity, and examine the evidence base for each option and suggest new areas for future research.

  16. 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, pindica 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.

  17. When syntax meets action: Brain potential evidence of overlapping between language and motor sequencing.

    Science.gov (United States)

    Casado, Pilar; Martín-Loeches, Manuel; León, Inmaculada; Hernández-Gutiérrez, David; Espuny, Javier; Muñoz, Francisco; Jiménez-Ortega, Laura; Fondevila, Sabela; de Vega, Manuel

    2018-03-01

    This study aims to extend the embodied cognition approach to syntactic processing. The hypothesis is that the brain resources to plan and perform motor sequences are also involved in syntactic processing. To test this hypothesis, Event-Related brain Potentials (ERPs) were recorded while participants read sentences with embedded relative clauses, judging for their acceptability (half of the sentences contained a subject-verb morphosyntactic disagreement). The sentences, previously divided into three segments, were self-administered segment-by-segment in two different sequential manners: linear or non-linear. Linear self-administration consisted of successively pressing three buttons with three consecutive fingers in the right hand, while non-linear self-administration implied the substitution of the finger in the middle position by the right foot. Our aim was to test whether syntactic processing could be affected by the manner the sentences were self-administered. Main results revealed that the ERPs LAN component vanished whereas the P600 component increased in response to incorrect verbs, for non-linear relative to linear self-administration. The LAN and P600 components reflect early and late syntactic processing, respectively. Our results convey evidence that language syntactic processing and performing non-linguistic motor sequences may share resources in the human brain. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Phytochemistry and potential therapeutic actions of Boswellic acids: A mini-review

    Directory of Open Access Journals (Sweden)

    Farah Iram

    2017-06-01

    Full Text Available The pentacyclic triterpenic acids isolated from the oleo gum resin of various Boswellia species are collectively called as Boswellic acids (BA. The oleo gum resin obtained from Indian variety i.e. Boswellia serrata (Family – Burseraceae is commonly known as Salai guggal. The resin fraction of Salai guggal is rich in Boswellic acids and its essential oil is composed of a mixture of mono, di and sesquiterpenes while gum fraction chiefly contains pentose and hexose sugars. This oleo-gum resin is quite popular among traditional practitioners of traditional Chinese and Indian Systems of medicine owing to their wide range of useful biological properties such as anti-inflammatory, anti-arthritic, anti-rheumatic, anti-diarrheal, anti-hyperlipidemic, anti-asthmatic, anti-cancer, anti-microbial anti-fungal, anti-complementary and analgesic activity, etc. It has been used as a herbal medicine since the prehistoric time to cure acute and chronic ailments including inflammatory diseases. Phytochemical investigation of this herbal medicine lead to identification of Boswellic acids which are found to be novel, potent, specific anti-inflammatory agents due to non-redox inhibition of 5-lipoxygenase (5-LO enzyme. However, the other important targets of Boswellic acids also include topoisomerases, angiogenesis, and cytochrome p450 enzymes. This review is a sincere attempt to discuss and present the current status of therapeutic potential, phytochemical as well as pharmacological profile of Boswellic acids primarily obtained from B. serrata.

  19. Efficacy of Morin as a Potential Therapeutic Phytocomponent: Insights into the Mechanism of Action

    Directory of Open Access Journals (Sweden)

    Amarendranath Choudhury

    2017-11-01

    Full Text Available Morin (3,5,7,29,49-pentahydroxyflavone is a yellow colour natural bioflavonoid abundantly available in different species of Moraceae family. Besides this, Morin is also harvested from several other sources like tea, coffee, cereals, fruits and red wine. Anti-oxidant, anti-inflammatory, and antiproliferative potency of Morin is well established in both in vivo and in vitro experiments. Among all major sources of Morin, Almond (Prunus dulcis, Fig (Chlorophora tinctoria, and Indian guava (Psidium guajava contains high quantity of it. Easy availability, less side effects and robust functional properties have encouraged the use of these plants in the traditional herbal medicine. In last few decades, the studies on Morin have opened up a whole new era in the therapeutic medicine. Besides anti-oxidant, anti-inflammatory, and antiproliferative activity, Morin has also been reported as a potential neuroprotective agent against many neurological diseases including Alzheimer’s disease, Parkinson’s disease, and cerebral ischemia. According to published reports, the underlying neuroprotective mechanism of Morin is focused mainly on its capacity to inhibit oxidative stress in brain. However, recent data also supports its efficacy in neuroprotection by effectively interacting in the β‒amyloid pathways, inflammatory pathways, and apoptotic pathways. In the present review, we have accumulated all the protective contributions of Morin and intended to drag a mechanistic pathway containing the molecular events leading to the protection against various anomalies.

  20. Quantitative motor unit action potential analysis of supraspinatus, infraspinatus, deltoideus and biceps femoris muscles in adult Royal Dutch sport horses.

    Science.gov (United States)

    Jose-Cunilleras, E; Wijnberg, I D

    2016-03-01

    Reference values for quantitative electromyography (QEMG) in shoulder and hindlimb muscles of horses are limited. To determine normative data on QEMG analysis of supraspinatus (SS), infraspinatus (IS), deltoideus (DT) and biceps femoris (BF) muscles. Experimental observational study and retrospective case series. Seven adult healthy Royal Dutch sport horses underwent quantitative motor unit action potential analysis of each muscle using commercial electromyography equipment. Measurements were made according to published methods. One-way ANOVA was used to compare quantitative motor unit action potential variables between muscles, with post hoc testing according to Bonferroni, with significance set at Paction potential were 8.7-10.4 ms, 651-867 μV, 3.2-3.7, 3.7-4.7, 1054-1457 μV·ms and 1.1-1.5 for SS, 9.6-11.0 ms, 779-1082 μV, 3.3-3.7, 3.8-4.7, 1349-2204 μV·ms and 1.4-1.9 for IS, 6.0-9.1 ms, 370-691 μV, 2.9-3.7, 2.8-4.5, 380-1374 μV·ms and 0.3-1.3 for DT and 5.7-7.8 ms, 265-385 μV, 2.7-3.2, 2.6-3.1, 296-484 μV·ms and 0.2-0.5 for BF, respectively. Mean duration, amplitude, number of phases and turns, area and size index were significantly (P15% polyphasic motor unit action potentials in SS and IS muscles. Differences between muscles should be taken into account when performing QEMG in order to be able to distinguish normal horses from horses with suspected neurogenic or myogenic disorders. These normal data provide the basis for objective QEMG assessment of shoulder and hindlimb muscles. Quantitative electromyography appears to be helpful in diagnosing neuropathies and discriminating these from myopathies. © 2015 EVJ Ltd.

  1. Investigation of the Dynamics of a Clamped-Clamped Microbeam Near the Third Mode Using a Partial Electrode

    KAUST Repository

    Masri, Karim M.

    2014-08-17

    We present an investigation of the dynamics of a clamped-clamped microbeam excited electrostatically near its third mode. To maximize the response at the third mode, a partial electrode configuration is utilized. A multi-mode Galerkin method is used to develop a reduced order model (ROM) of the beam. A shooting method to find the periodic motion is utilized to generate frequency response curves. The curves show hardenining behavior and dynamic pull-in. We show that the dynamic amplitude of the partial configuration is higher than that of a full electrode configuration. These results are promising for the use of higher-order modes for mass detection and for ultra sensitive resonant sensors.

  2. Investigation of the Dynamics of a Clamped-Clamped Microbeam Near the Third Mode Using a Partial Electrode

    KAUST Repository

    Masri, Karim M.; Younis, Mohammad I.

    2014-01-01

    We present an investigation of the dynamics of a clamped-clamped microbeam excited electrostatically near its third mode. To maximize the response at the third mode, a partial electrode configuration is utilized. A multi-mode Galerkin method is used to develop a reduced order model (ROM) of the beam. A shooting method to find the periodic motion is utilized to generate frequency response curves. The curves show hardenining behavior and dynamic pull-in. We show that the dynamic amplitude of the partial configuration is higher than that of a full electrode configuration. These results are promising for the use of higher-order modes for mass detection and for ultra sensitive resonant sensors.

  3. 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.

  4. Defining the action spectrum of potential PGC-1α activators on a mitochondrial and cellular level in vivo.

    Science.gov (United States)

    Hofer, Annette; Noe, Natalie; Tischner, Christin; Kladt, Nikolay; Lellek, Veronika; Schauß, Astrid; Wenz, Tina

    2014-05-01

    Previous studies have demonstrated a therapeutic benefit of pharmaceutical PGC-1α activation in cellular and murine model of disorders linked to mitochondrial dysfunction. While in some cases, this effect seems to be clearly associated with boosting of mitochondrial function, additional alterations as well as tissue- and cell-type-specific effects might play an important role. We initiated a comprehensive analysis of the effects of potential PGC-1α-activating drugs and pharmaceutically targeted the PPAR (bezafibrate, rosiglitazone), AMPK (AICAR, metformin) and Sirt1 (resveratrol) pathways in HeLa cells, neuronal cells and PGC-1α-deficient MEFs to get insight into cell type specificity and PGC-1α dependence of their working action. We used bezafibrate as a model drug to assess the effect on a tissue-specific level in a murine model. Not all analyzed drugs activate the PGC pathway or alter mitochondrial protein levels. However, they all affect supramolecular assembly of OXPHOS complexes and OXPHOS protein stability. In addition, a clear drug- and cell-type-specific influence on several cellular stress pathways as well as on post-translational modifications could be demonstrated, which might be relevant to fully understand the action of the analyzed drugs in the disease state. Importantly, the effect on the activation of mitochondrial biogenesis and stress response program upon drug treatment is PGC-1α dependent in MEFs demonstrating not only the pleiotropic effects of this molecule but points also to the working mechanism of the analyzed drugs. The definition of the action spectrum of the different drugs forms the basis for a defect-specific compensation strategy and a future personalized therapeutic approach.

  5. Potential Causes of Significant Inventory Differences at Bulk Handling Facilities and the Importance of Inventory Difference Action Levels

    International Nuclear Information System (INIS)

    Homer, Alan; O’Hagan, Brendan

    2015-01-01

    Accountancy for nuclear material can be split into two categories. Firstly, where possible, accountancy should be in terms of items that can be transferred as discrete packages and their contents fixed at the time of their creation. All items must remain accounted for at all times, and a single missing item is considered significant. Secondly, where nuclear material is unconstrained, for example in a reprocessing plant where it can change form, there is an uncertainty that relates to the amount of material present in any location. Cumulatively, these uncertainties can be summed and provide a context for any estimate of material in a process. Any apparent loss or gain between what has been physically measured within a facility during its physical inventory take and what is reported within its nuclear material accounts is known as an inventory difference. The cumulative measurement uncertainties can be used to set an action level for the inventory difference so that if an inventory difference is observed outside of such action levels, the difference is classified as significant and an investigation to find the root cause(s) is required. The purpose of this paper is to explore the potential causes of significant inventory differences and to provide a framework within which an inventory difference investigation can be carried out.

  6. An update on potential molecular mechanisms underlying the actions of snake venom L-amino acid oxidases (LAAOs).

    Science.gov (United States)

    Paloschi, Mauro Valentino; Pontes, Adriana Silva; Soares, Andreimar Martins; Zuliani, Juliana Pavan

    2017-11-08

    LAAOs (EC 1.4.3.2) are found in concentrations that vary according to each species of snakes; Viperidae, Crotalidae and Elapidae contain 1-9% of this enzyme in their venoms. This review focuses on an update on molecular mechanisms, platelet activities, antimicrobial, antiprotozoal, induction of apoptosis and inflammatory potential underlying the actions of SV-LAAOs. Snake venom LAAOs (SV-LAAOs) have become an interesting subject for pharmacological, structural and molecular studies. Although the mechanisms of action of these enzymes are not well understood they are a subject of a variety of studies, because LAAOs are multifunctional enzymes exhibiting a wide range of pharmacological effects, including the inhibition or induction of platelet aggregation, hemolysis and hemorrhage, in addition to the stimulation of apoptosis, the activation of leukocytes and the formation of edema. Moreover, SV-LAAOs play an important role in bactericidal, cytotoxic, anti-parasitic, anti-tumor, and antiviral activities. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Effect of DSPE-PEG on compound action potential, injury potential and ion concentration following compression in ex vivo spinal cord.

    Science.gov (United States)

    Wang, Aihua; Huo, Xiaolin; Zhang, Guanghao; Wang, Xiaochen; Zhang, Cheng; Wu, Changzhe; Rong, Wei; Xu, Jing; Song, Tao

    2016-05-04

    It has been shown that polyethylene glycol (PEG) can reseal membrane disruption on the spinal cord, but only high concentrations of PEG have been shown to have this effect. Therefore, the effect of PEG is somewhat limited, and it is necessary to investigate a new approach to repair spinal cord injury. This study assesses the ability of 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(poly (ethylene glycol)) 2000] (DSPE-PEG) to recover physiological function and attenuate the injury-induced influx of extracellular ions in ex vivo spinal cord injury. Isolated spinal cords were subjected to compression injury and treated with PEG or DSPE-PEG immediately after injury. The compound action potential (CAP) was recorded before and after injury to assess the functional recovery. Furthermore, injury potential, the difference in gap potentials before and after compression, and the concentration of intracellular ions were used to evaluate the effect of DSPE-PEG on reducing ion influx. Data showed that the injury potential and ion concentration of the untreated, PEG and DSPE-PEG group, without significant difference among them, are remarkably higher than those of the intact group. Moreover, the CAP recovery of the DSPE-PEG and PEG treated spinal cords was significantly greater than that of the untreated spinal cords. The level of CAP recovery in the DSPE-PEG and PEG treated groups was the same, but the concentration of DSPE-PEG used was much lower than the concentration of PEG. These results suggest that instant application of DSPE-PEG could effectively repair functional disturbance in SCI at a much lower concentration than PEG. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. 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.

  9. [Value of condensation and rarefaction click evoked action potential latency difference in the diagnosis of Meniere's disease].

    Science.gov (United States)

    Wang, Z; Shao, X; Yan, W; Lin, H

    2000-06-01

    To study the value of condensation and rarefaction clicks evoked action potential (AP) latency difference (LD) in diagnosis of Meniere's disease. AP was recorded with ECochG in controls (50 ears) and patients with Meniere's disease(90 ears) and sensorineural hearing loss(SNHL) of other origins(60 ears). LD was calculated and analyzed. LD in patients with Meniere's disease was (0.30 +/- 0.15) ms, which was significantly larger than that of controls(0.18 +/- 0.07) ms and of patients with SNHL of other origins(0.20 +/- 0.10) ms (P curve was larger than those with flat auditory sensation curve(P rarefaction click evoked AP latency difference can be an objective parameter in diagnosis of Meniere's disease.

  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. Changes in contractile properties and action potentials of motor units in the rat medial gastrocnemius muscle during maturation.

    Science.gov (United States)

    Dobrzynska, Z; Celichowski, J

    2016-02-01

    The early phase of development of muscles stops following the disappearance of embryonic and neonatal myosin and the elimination of polyneuronal innervation of muscle fibres with the formation of motor units (MUs), but later the muscle mass still considerably increases. It is unknown whether the three types are visible among newly formed MUs soon after the early postnatal period and whether their proportion is similar to that in adult muscle. Moreover, the processes responsible for MU-force regulation by changes in motoneuronal firing rate as well as properties of motor unit action potentials (MUAPs) during maturation are unknown. Three groups of Wistar rats were investigated - 1 month old, 2 months old and the adult, 9 months old. The basic contractile properties and action potentials of MUs in the medial gastrocnemius (MG) muscle were analysed. The three types of MUs were distinguishable in all age groups, but higher proportion of slow MUs was noticed in young rats (29%, 18% and 11% in 1, 2 and 9 months rats, respectively). The fatigue index for fast fatigable MUs in 1 month old rats was about 2 times higher than in 9 months old rats. The twitch time parameters of fast MUs were shortened during the maturation; for these units, the force-frequency curves in young rats were shifted towards lower frequencies, which suggested that fast motoneurons of young animals generate lower firing rates. Higher twitch-to-tetanus ratios noted for the three MU types in young rats suggested the smaller role of rate coding in force regulation processes, and the higher role of MU recruitment in young rats. No significant differences in MUAP parameters between two groups of young and adult animals were observed. Concluding, the maturation process evokes deeper changes in fast MUs than in slow ones.

  12. 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

  13. Cannabinoid actions at TRPV channels: effects on TRPV3 and TRPV4 and their potential relevance to gastrointestinal inflammation.

    Science.gov (United States)

    De Petrocellis, L; Orlando, P; Moriello, A Schiano; Aviello, G; Stott, C; Izzo, A A; Di Marzo, V

    2012-02-01

    Plant cannabinoids, like Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD), activate/desensitize thermosensitive transient receptor potential (TRP) channels of vanilloid type-1 or -2 (TRPV1 or TRPV2). We investigated whether cannabinoids also activate/desensitize two other 'thermo-TRP's', the TRP channels of vanilloid type-3 or -4 (TRPV3 or TRPV4), and if the TRPV-inactive cannabichromene (CBC) modifies the expression of TRPV1-4 channels in the gastrointestinal tract. TRP activity was assessed by evaluating elevation of [Ca(2+)](i) in rat recombinant TRPV3- and TRPV4-expressing HEK-293 cells. TRP channel mRNA expression was measured by quantitative RT-PCR in the jejunum and ileum of mice treated with vehicle or the pro-inflammatory agent croton oil. (i) CBD and tetrahydrocannabivarin (THCV) stimulated TRPV3-mediated [Ca(2+)](i) with high efficacy (50-70% of the effect of ionomycin) and potency (EC(50∼) 3.7 μm), whereas cannabigerovarin (CBGV) and cannabigerolic acid (CBGA) were significantly more efficacious at desensitizing this channel to the action of carvacrol than at activating it; (ii) cannabidivarin and THCV stimulated TRPV4-mediated [Ca(2+)](i) with moderate-high efficacy (30-60% of the effect of ionomycin) and potency (EC(50) 0.9-6.4 μm), whereas CBGA, CBGV, cannabinol and cannabigerol were significantly more efficacious at desensitizing this channel to the action of 4-α-phorbol 12,13-didecanoate (4α-PDD) than at activating it; (iii) CBC reduced TRPV1β, TRPV3 and TRPV4 mRNA in the jejunum, and TRPV3 and TRPV4 mRNA in the ileum of croton oil-treated mice. Cannabinoids can affect both the activity and the expression of TRPV1-4 channels, with various potential therapeutic applications, including in the gastrointestinal tract. © 2011 The Authors. Acta Physiologica © 2011 Scandinavian Physiological Society.

  14. Effect of acute stretch injury on action potential and network activity of rat neocortical neurons in culture.

    Science.gov (United States)

    Magou, George C; Pfister, Bryan J; Berlin, Joshua R

    2015-10-22

    The basis for acute seizures following traumatic brain injury (TBI) remains unclear. Animal models of TBI have revealed acute hyperexcitablility in cortical neurons that could underlie seizure activity, but studying initiating events causing hyperexcitability is difficult in these models. In vitro models of stretch injury with cultured cortical neurons, a surrogate for TBI, allow facile investigation of cellular changes after injury but they have only demonstrated post-injury hypoexcitability. The goal of this study was to determine if neuronal hyperexcitability could be triggered by in vitro stretch injury. Controlled uniaxial stretch injury was delivered to a spatially delimited region of a spontaneously active network of cultured rat cortical neurons, yielding a region of stretch-injured neurons and adjacent regions of non-stretched neurons that did not directly experience stretch injury. Spontaneous electrical activity was measured in non-stretched and stretch-injured neurons, and in control neuronal networks not subjected to stretch injury. Non-stretched neurons in stretch-injured cultures displayed a three-fold increase in action potential firing rate and bursting activity 30-60 min post-injury. Stretch-injured neurons, however, displayed dramatically lower rates of action potential firing and bursting. These results demonstrate that acute hyperexcitability can be observed in non-stretched neurons located in regions adjacent to the site of stretch injury, consistent with reports that seizure activity can arise from regions surrounding the site of localized brain injury. Thus, this in vitro procedure for localized neuronal stretch injury may provide a model to study the earliest cellular changes in neuronal function associated with acute post-traumatic seizures. Copyright © 2015. Published by Elsevier B.V.

  15. A second-generation computational modeling of cardiac electrophysiology: response of action potential to ionic concentration changes and metabolic inhibition.

    Science.gov (United States)

    Alaa, Nour Eddine; Lefraich, Hamid; El Malki, Imane

    2014-10-21

    Cardiac arrhythmias are becoming one of the major health care problem in the world, causing numerous serious disease conditions including stroke and sudden cardiac death. Furthermore, cardiac arrhythmias are intimately related to the signaling ability of cardiac cells, and are caused by signaling defects. Consequently, modeling the electrical activity of the heart, and the complex signaling models that subtend dangerous arrhythmias such as tachycardia and fibrillation, necessitates a quantitative model of action potential (AP) propagation. Yet, many electrophysiological models, which accurately reproduce dynamical characteristic of the action potential in cells, have been introduced. However, these models are very complex and are very time consuming computationally. Consequently, a large amount of research is consecrated to design models with less computational complexity. This paper is presenting a new model for analyzing the propagation of ionic concentrations and electrical potential in space and time. In this model, the transport of ions is governed by Nernst-Planck flux equation (NP), and the electrical interaction of the species is described by a new cable equation. These set of equations form a system of coupled partial nonlinear differential equations that is solved numerically. In the first we describe the mathematical model. To realize the numerical simulation of our model, we proceed by a finite element discretization and then we choose an appropriate resolution algorithm. We give numerical simulations obtained for different input scenarios in the case of suicide substrate reaction which were compared to those obtained in literature. These input scenarios have been chosen so as to provide an intuitive understanding of dynamics of the model. By accessing time and space domains, it is shown that interpreting the electrical potential of cell membrane at steady state is incorrect. This model is general and applies to ions of any charge in space and time

  16. Insulin action in human thighs after one-legged immobilization

    DEFF Research Database (Denmark)

    Richter, Erik; Kiens, Bente; Mizuno, M.

    1989-01-01

    Insulin action was assessed in thighs of five healthy young males who had one knee immobilized for 7 days by a splint. The splint was not worn in bed. Subjects also used crutches to prevent weight bearing of the immobilized leg. Immobilization decreased the activity of citrate synthase and 3-OH......-acyl-CoA-dehydrogenase in the vastus lateralis muscle by 9 and 14%, respectively, and thigh volume by 5%. After 7 days of immobilization, a two-step euglycemic hyperinsulinemic clamp procedure combined with arterial and bilateral femoral venous catheterization was performed. Insulin action on glucose uptake and tyrosine release...... of the thighs at mean plasma insulin concentrations of 67 (clamp step I) and 447 microU/ml (clamp step II) was decreased by immobilization, whereas immobilization did not affect insulin action on thigh exchange of free fatty acids, glycerol, O2, or potassium. Before and during the clamp step I, lactate release...

  17. Clamped seismic metamaterials: ultra-low frequency stop bands

    International Nuclear Information System (INIS)

    Achaoui, Y; Enoch, S; Guenneau, S; Antonakakis, T; Brûlé, S; Craster, R V

    2017-01-01

    The regularity of earthquakes, their destructive power, and the nuisance of ground vibration in urban environments, all motivate designs of defence structures to lessen the impact of seismic and ground vibration waves on buildings. Low frequency waves, in the range 1–10 Hz for earthquakes and up to a few tens of Hz for vibrations generated by human activities, cause a large amount of damage, or inconvenience; depending on the geological conditions they can travel considerable distances and may match the resonant fundamental frequency of buildings. The ultimate aim of any seismic metamaterial, or any other seismic shield, is to protect over this entire range of frequencies; the long wavelengths involved, and low frequency, have meant this has been unachievable to date. Notably this is scalable and the effects also hold for smaller devices in ultrasonics. There are three approaches to obtaining shielding effects: bragg scattering, locally resonant sub-wavelength inclusions and zero-frequency stop-band media. The former two have been explored, but the latter has not and is examined here. Elastic flexural waves, applicable in the mechanical vibrations of thin elastic plates, can be designed to have a broad zero-frequency stop-band using a periodic array of very small clamped circles. Inspired by this experimental and theoretical observation, all be it in a situation far removed from seismic waves, we demonstrate that it is possible to achieve elastic surface (Rayleigh) wave reflectors at very large wavelengths in structured soils modelled as a fully elastic layer periodically clamped to bedrock. We identify zero frequency stop-bands that only exist in the limit of columns of concrete clamped at their base to the bedrock. In a realistic configuration of a sedimentary basin 15 m deep we observe a zero frequency stop-band covering a broad frequency range of 0–30 Hz. (paper)

  18. The activity of spontaneous action potentials in developing hair cells is regulated by Ca(2+-dependence of a transient K+ current.

    Directory of Open Access Journals (Sweden)

    Snezana Levic

    Full Text Available Spontaneous action potentials have been described in developing sensory systems. These rhythmic activities may have instructional roles for the functional development of synaptic connections. The importance of spontaneous action potentials in the developing auditory system is underpinned by the stark correlation between the time of auditory system functional maturity, and the cessation of spontaneous action potentials. A prominent K(+ current that regulates patterning of action potentials is I(A. This current undergoes marked changes in expression during chicken hair cell development. Although the properties of I(A are not normally classified as Ca(2+-dependent, we demonstrate that throughout the development of chicken hair cells, I(A is greatly reduced by acute alterations of intracellular Ca(2+. As determinants of spike timing and firing frequency, intracellular Ca(2+ buffers shift the activation and inactivation properties of the current to more positive potentials. Our findings provide evidence to demonstrate that the kinetics and functional expression of I(A are tightly regulated by intracellular Ca(2+. Such feedback mechanism between the functional expression of I(A and intracellular Ca(2+ may shape the activity of spontaneous action potentials, thus potentially sculpting synaptic connections in an activity-dependent manner in the developing cochlea.

  19. [Time of cord clamping and neonatal complications, a prospective study].

    Science.gov (United States)

    Rincón, D; Foguet, A; Rojas, M; Segarra, E; Sacristán, E; Teixidor, R; Ortega, A

    2014-09-01

    To assess the effects of early or late clamping of the umbilical cord in term newborns, assessing the levels of hemoglobin, hematocrit, and ferritin, and their correlation with some of the complications. A prospective study of healthy newborns at term or born by dystotic or eutocic delivery in our hospital between May 2009 until May 2010. Patients were assigned according to the time of clamping, group 1 (<60 seconds), group 2 (1 to<2 minutes), and group 3 (2 to 3 minutes). Laboratory tests were performed at birth and at 48 hours of life, assessing the levels of hemoglobin, hematocrit, ferritin, and bilirubin. The risk of polycythemia, respiratory distress syndrome, neonatal phototherapy or admission to the Intensive Care Unit and the hospital stay, were evaluated. A total of 242 patients were included: group 1 (g1=80), group 2 (g2=31) y group 3 (g3=131). The background maternal and neonatal characteristics were similar in all sets. The first test showed significant differences in ferritin levels in those infants with delayed clamping (g1: 111 mg/dl, g2: 125 mg/dl, g3: 173 mg/dl; p<0.01). In the second analysis the values of hemoglobin (g1: 17.3 g/dl, g2: 18.9 g/dl, g3: 19.2 g/dl; p<0.01), hematocrit (g1: 53.4%, g2: 58%, g3: 59%; p<0.01) and ferritin (g1: 254 mg/dl, g2: 254.7 mg/dl, g3: 313 mg/dl; p = 0.008) were statistically higher in this group. As regards complications, a significant increase was observed in the number of cases of polycythemia symptoms in group 3. The late cord clamping is associated with an increase in hematocrit, hemoglobin and ferritin at 48 hours of life, as well as an increased risk of polycythemia present with symptoms. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  20. A new configuration for multilevel converters with diode clamped topology

    DEFF Research Database (Denmark)

    Nami, A.; Zare, F.; Ledwich, G.

    2008-01-01

    Due to the increased use of renewable energy and power elctronic applications, more multilevel converters (MLC) are developed. A Neutral Point Clamped (NPC) inverter is one of the most used multilevel topologies for wind turbine (WT) and photovoltaic (PV) applications. One of the most crucial...... of load changes which can avoid neutral point balancing problem in such converters. In addition, the presented topology is suitable for renewable energy systems to boost the low rectified output-voltage. In order to verify the proposed topology, steady state analysis, modelling and simulations are carried...

  1. Five-level Z-source diode-clamped inverter

    DEFF Research Database (Denmark)

    Gao, F.; Loh, Poh Chiang; Blaabjerg, Frede

    2010-01-01

    This study proposes a five-level Z-source diode-clamped inverter designed with two intermediate Z-source networks connected between the dc input sources and rear-end inverter circuitry. By partially shorting the Z-source networks, new operating states not previously reported for two-level Z......-source inverter are introduced here for operating the proposed inverter with voltage buck–boost energy conversion ability and five-level phase voltage switching. These characteristic features are in fact always ensured at the inverter terminal output by simply adopting a properly designed carrier modulation...

  2. Potassium Chloride Versus Voltage Clamp Contractures in Ventricular Muscle

    Science.gov (United States)

    Morad, M.; Reeck, S.; Rao, M.

    1981-01-01

    In frog ventricle, developed tension was markedly larger in response to depolarization caused by a voltage clamp step than to depolarization induced by high concentrations of potassium chloride. Measurement of extracellular potassium activity at the surface and at the depth of muscle during the development of contractures showed that the diffusion of potassium is much slower than the spread of depolarization through the cross section of muscle. These two observations suggest that competition between the depolarizing and the negative inotropic effects of an increase in the extracellular potassium ion concentration may determine the time course and magnitude of contractile tension in heart muscle.

  3. Equivalent circuit of frog atrial tissue as determined by voltage clamp-unclamp experiments.

    Science.gov (United States)

    Tarr, M; Trank, J

    1971-11-01

    The equivalent circuit that has been used in the analysis of nerve voltage-clamp data is that of the membrane capacity in parallel with the membrane resistance. Voltage-clamp experiments on frog atrial tissue indicate that this circuit will not suffice for this cardiac tissue. The change in membrane current associated with a step change in membrane potential does not show a rapid spike of capacitive current as would be expected for the simple parallel resistance-capacitance network. Rather, there is a step change in current followed by an exponential decay in current with a time constant of about 1 msec. This relatively slow capacitive charging current suggests that there is a resistance in series with the membrane capacity. A possible equivalent circuit is that of a series resistance external to the parallel resistance-capacitance network of the cell membranes. Another possible circuit assumes that the series resistance is an integral part of the cell membrane. The data presented in this paper demonstrate that the equivalent circuit of a bundle of frog atrial muscle is that of an external resistance in series with the cell membranes.

  4. Planar Diamond-Based Multiarrays to Monitor Neurotransmitter Release and Action Potential Firing: New Perspectives in Cellular Neuroscience.

    Science.gov (United States)

    Carabelli, Valentina; Marcantoni, Andrea; Picollo, Federico; Battiato, Alfio; Bernardi, Ettore; Pasquarelli, Alberto; Olivero, Paolo; Carbone, Emilio

    2017-02-15

    High biocompatibility, outstanding electrochemical responsiveness, inertness, and transparency make diamond-based multiarrays (DBMs) first-rate biosensors for in vitro detection of electrochemical and electrical signals from excitable cells together, with potential for in vivo applications as neural interfaces and prostheses. Here, we will review the electrochemical and physical properties of various DBMs and how these devices have been employed for recording released neurotransmitter molecules and all-or-none action potentials from living cells. Specifically, we will overview how DBMs can resolve localized exocytotic events from subcellular compartments using high-density microelectrode arrays (MEAs), or monitoring oxidizable neurotransmitter release from populations of cells in culture and tissue slices using low-density MEAs. Interfacing DBMs with excitable cells is currently leading to the promising opportunity of recording electrical signals as well as creating neuronal interfaces through the same device. Given the recent increasingly growing development of newly available DBMs of various geometries to monitor electrical activity and neurotransmitter release in a variety of excitable and neuronal tissues, the discussion will be limited to planar DBMs.

  5. Effect of microbial action on the corrosion potential of austenitic alloy containers for high-level nuclear waste

    International Nuclear Information System (INIS)

    Angell, P.; Dunn, D.S.; Cragnolino, G.A.

    1996-01-01

    The safe disposal of high-level nuclear waste (HLW) entails the ability to ensure the integrity of waste containers for prolonged time periods. It is generally accepted that under certain conditions, microbial action may change local benign environments to those in which localized corrosion can be actively promoted. The use of repassivation potential (E rp ) in relation to the value of the corrosion potential (E corr ) has been proposed as a means of assessing the propensity of a metallic material to localized corrosion. Microbial activity is known to influence E corr however, the precise mechanism is unresolved. Shewanella putrefaciens, a bacteria with many of the characteristics of sulfate-reducing bacteria (SRB), are being grown under controlled conditions on 316L stainless steel (SS) surfaces to understand the relationship between E corr and metabolic activity. It has been observed that the growth of the bacteria under aerobic conditions, without the production of metabolic sulfide, leads to only minor variation in E corr . These changes possibly correlate to the periods of active bacterial growth

  6. 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.

  7. 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

  8. Assessing the Electrode-Neuron Interface with the Electrically Evoked Compound Action Potential, Electrode Position, and Behavioral Thresholds.

    Science.gov (United States)

    DeVries, Lindsay; Scheperle, Rachel; Bierer, Julie Arenberg

    2016-06-01

    Variability in speech perception scores among cochlear implant listeners may largely reflect the variable efficacy of implant electrodes to convey stimulus information to the auditory nerve. In the present study, three metrics were applied to assess the quality of the electrode-neuron interface of individual cochlear implant channels: the electrically evoked compound action potential (ECAP), the estimation of electrode position using computerized tomography (CT), and behavioral thresholds using focused stimulation. The primary motivation of this approach is to evaluate the ECAP as a site-specific measure of the electrode-neuron interface in the context of two peripheral factors that likely contribute to degraded perception: large electrode-to-modiolus distance and reduced neural density. Ten unilaterally implanted adults with Advanced Bionics HiRes90k devices participated. ECAPs were elicited with monopolar stimulation within a forward-masking paradigm to construct channel interaction functions (CIF), behavioral thresholds were obtained with quadrupolar (sQP) stimulation, and data from imaging provided estimates of electrode-to-modiolus distance and scalar location (scala tympani (ST), intermediate, or scala vestibuli (SV)) for each electrode. The width of the ECAP CIF was positively correlated with electrode-to-modiolus distance; both of these measures were also influenced by scalar position. The ECAP peak amplitude was negatively correlated with behavioral thresholds. Moreover, subjects with low behavioral thresholds and large ECAP amplitudes, averaged across electrodes, tended to have higher speech perception scores. These results suggest a potential clinical role for the ECAP in the objective assessment of individual cochlear implant channels, with the potential to improve speech perception outcomes.

  9. Small Molecules for Early Endosome-Specific Patch Clamping.

    Science.gov (United States)

    Chen, Cheng-Chang; Butz, Elisabeth S; Chao, Yu-Kai; Grishchuk, Yulia; Becker, Lars; Heller, Stefan; Slaugenhaupt, Susan A; Biel, Martin; Wahl-Schott, Christian; Grimm, Christian

    2017-07-20

    To resolve the subcellular distribution of endolysosomal ion channels, we have established a novel experimental approach to selectively patch clamp Rab5 positive early endosomes (EE) versus Rab7/LAMP1-positive late endosomes/lysosomes (LE/LY). To functionally characterize ion channels in endolysosomal membranes with the patch-clamp technique, it is important to develop techniques to selectively enlarge the respective organelles. We found here that two small molecules, wortmannin and latrunculin B, enlarge Rab5-positive EE when combined but not Rab7-, LAMP1-, or Rab11 (RE)-positive vesicles. The two compounds act rapidly, specifically, and are readily applicable in contrast to genetic approaches or previously used compounds such as vacuolin, which enlarges EE, RE, and LE/LY. We apply this approach here to measure currents mediated by TRPML channels, in particular TRPML3, which we found to be functionally active in both EE and LE/LY in overexpressing cells as well as in endogenously expressing CD11b+ lung-tissue macrophages. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Investigating ion channel conformational changes using voltage clamp fluorometry.

    Science.gov (United States)

    Talwar, Sahil; Lynch, Joseph W

    2015-11-01

    Ion channels are membrane proteins whose functions are governed by conformational changes. The widespread distribution of ion channels, coupled with their involvement in most physiological and pathological processes and their importance as therapeutic targets, renders the elucidation of these conformational mechanisms highly compelling from a drug discovery perspective. Thanks to recent advances in structural biology techniques, we now have high-resolution static molecular structures for members of the major ion channel families. However, major questions remain to be resolved about the conformational states that ion channels adopt during activation, drug modulation and desensitization. Patch-clamp electrophysiology has long been used to define ion channel conformational states based on functional criteria. It achieves this by monitoring conformational changes at the channel gate and cannot detect conformational changes occurring in regions distant from the gate. Voltage clamp fluorometry involves labelling cysteines introduced into domains of interest with environmentally sensitive fluorophores and inferring structural rearrangements from voltage or ligand-induced fluorescence changes. Ion channel currents are monitored simultaneously to verify the conformational status. By defining real time conformational changes in domains distant from the gate, this technique provides unexpected new insights into ion channel structure and function. This review aims to summarise the methodology and highlight recent innovative applications of this powerful technique. This article is part of the Special Issue entitled 'Fluorescent Tools in Neuropharmacology'. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Failure of action potential propagation in sensory neurons: mechanisms and loss of afferent filtering in C-type units after painful nerve injury

    NARCIS (Netherlands)

    Gemes, Geza; Koopmeiners, Andrew; Rigaud, Marcel; Lirk, Philipp; Sapunar, Damir; Bangaru, Madhavi Latha; Vilceanu, Daniel; Garrison, Sheldon R.; Ljubkovic, Marko; Mueller, Samantha J.; Stucky, Cheryl L.; Hogan, Quinn H.

    2013-01-01

    The T-junction of sensory neurons in the dorsal root ganglion (DRG) is a potential impediment to action potential (AP) propagation towards the CNS. Using intracellular recordings from rat DRG neuronal somata during stimulation of the dorsal root, we determined that the maximal rate at which all of

  12. Impact of sarcoplasmic reticulum calcium release on calcium dynamics and action potential morphology in human atrial myocytes: a computational study.

    Directory of Open Access Journals (Sweden)

    Jussi T Koivumäki

    Full Text Available Electrophysiological studies of the human heart face the fundamental challenge that experimental data can be acquired only from patients with underlying heart disease. Regarding human atria, there exist sizable gaps in the understanding of the functional role of cellular Ca²+ dynamics, which differ crucially from that of ventricular cells, in the modulation of excitation-contraction coupling. Accordingly, the objective of this study was to develop a mathematical model of the human atrial myocyte that, in addition to the sarcolemmal (SL ion currents, accounts for the heterogeneity of intracellular Ca²+ dynamics emerging from a structurally detailed sarcoplasmic reticulum (SR. Based on the simulation results, our model convincingly reproduces the principal characteristics of Ca²+ dynamics: 1 the biphasic increment during the upstroke of the Ca²+ transient resulting from the delay between the peripheral and central SR Ca²+ release, and 2 the relative contribution of SL Ca²+ current and SR Ca²+ release to the Ca²+ transient. In line with experimental findings, the model also replicates the strong impact of intracellular Ca²+ dynamics on the shape of the action potential. The simulation results suggest that the peripheral SR Ca²+ release sites define the interface between Ca²+ and AP, whereas the central release sites are important for the fire-diffuse-fire propagation of Ca²+ diffusion. Furthermore, our analysis predicts that the modulation of the action potential duration due to increasing heart rate is largely mediated by changes in the intracellular Na+ concentration. Finally, the results indicate that the SR Ca²+ release is a strong modulator of AP duration and, consequently, myocyte refractoriness/excitability. We conclude that the developed model is robust and reproduces many fundamental aspects of the tight coupling between SL ion currents and intracellular Ca²+ signaling. Thus, the model provides a useful framework for future

  13. Study of crotoxin mechanism of action to mammary carcinomas and evaluation of its potential as a radiopharmaceutical

    International Nuclear Information System (INIS)

    Silveira, Marina Bicalho

    2010-01-01

    Crotoxin, the main component of Crotalus durissus terrificus snake venom, has been studied since 1938. It is a natural polypeptidic complex with pharmacological potential because of its antitumoral properties which has attracted great interest for diagnosis and therapy of oncological diseases. However, Crotoxin mechanism of action and sites of specific interaction on tumor cells are still misunderstood. Breast cancer is the second most frequent type in the world and the most common cancer in women. About 30 to 60% of mammary tumors overexpress epidermal growth factor receptor (EGFR), a transmembrane protein related to cell proliferation. Since literature has reported that Crotoxin antitumoral effect is more potent on cells with EGFR overexpression the objectives of this work were to evaluate Crotoxin cytotoxic effects on mammary tumor cells human breast carcinoma (MCF-7) and Ehrlich tumor cells (murine ascitics carcinoma), and to investigate the specific molecular interaction of Crotoxin on Ehrlich tumor cells. Initially, Crotoxin was radiolabelled with iodine-125 ( 125 I-Crotoxin) and iodine-131 ( 131 I-Crotoxin). Saturation and competition assay were carried out to characterize Crotoxin in vitro interaction; Crotoxin biodistribution studies and singlephoton emission computed tomography (SPECT) of mice bearing Ehrlich tumor have been evaluated to describe in vivo interaction. Our results showed that Crotoxin presented cytotoxic effect against Ehrlich with DL 50 in vitro (concentration of compound which is lethal for 50% of cells) of about one micromolar, but did not present significant effect against MCF-7. Morphological alterations characteristic of apoptosis suggests programmed cell death. 125 I-Crotoxin interaction with Ehrlich tumor cells was saturable with approximately 70% specificity, and presented K d =24.98 nmol/L and B max =16,570 sites/cell for low affinity binding sites and K d =0.06 nmol/L and B max =210 sites/cell high affinity binding sites

  14. Contribution of two-pore K+ channels to cardiac ventricular action potential revealed using human iPSC-derived cardiomyocytes.

    Science.gov (United States)

    Chai, Sam; Wan, Xiaoping; Nassal, Drew M; Liu, Haiyan; Moravec, Christine S; Ramirez-Navarro, Angelina; Deschênes, Isabelle

    2017-06-01

    Two-pore K + (K 2p ) channels have been described in modulating background conductance as leak channels in different physiological systems. In the heart, the expression of K 2p channels is heterogeneous with equivocation regarding their functional role. Our objective was to determine the K 2p expression profile and their physiological and pathophysiological contribution to cardiac electrophysiology. Induced pluripotent stem cells (iPSCs) generated from humans were differentiated into cardiomyocytes (iPSC-CMs). mRNA was isolated from these cells, commercial iPSC-CM (iCells), control human heart ventricular tissue (cHVT), and ischemic (iHF) and nonischemic heart failure tissues (niHF). We detected 10 K 2p channels in the heart. Comparing quantitative PCR expression of K 2p channels between human heart tissue and iPSC-CMs revealed K 2p 1.1, K 2p 2.1, K 2p 5.1, and K 2p 17.1 to be higher expressed in cHVT, whereas K 2p 3.1 and K 2p 13.1 were higher in iPSC-CMs. Notably, K 2p 17.1 was significantly lower in niHF tissues compared with cHVT. Action potential recordings in iCells after K 2p small interfering RNA knockdown revealed prolongations in action potential depolarization at 90% repolarization for K 2p 2.1, K 2p 3.1, K 2p 6.1, and K 2p 17.1. Here, we report the expression level of 10 human K 2p channels in iPSC-CMs and how they compared with cHVT. Importantly, our functional electrophysiological data in human iPSC-CMs revealed a prominent role in cardiac ventricular repolarization for four of these channels. Finally, we also identified K 2p 17.1 as significantly reduced in niHF tissues and K 2p 4.1 as reduced in niHF compared with iHF. Thus, we advance the notion that K 2p channels are emerging as novel players in cardiac ventricular electrophysiology that could also be remodeled in cardiac pathology and therefore contribute to arrhythmias. NEW & NOTEWORTHY Two-pore K + (K 2p ) channels are traditionally regarded as merely background leak channels in myriad

  15. 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…

  16. Loss Distribution Analysis of Three-Level Active Neutral-Point-Clamped (3L-ANPC) Converter with Different PWM Strategies

    DEFF Research Database (Denmark)

    Zhang, Gang; Yang, Yongheng; Iannuzzo, Francesco

    2016-01-01

    The three-level (3L) Active Neutral-Point-Clamped (ANPC) topology has been introduced to resolve the uneven loss distribution issue in the classical 3L Neutral-Point-Clamped (NPC) topology. This Pulse-Width-Modulation (PWM) strategy is then an important means to fully explore the potential benefits...... are separated in order to improve the loss distribution among the power devices. A comparison between the proposed strategy and other major PWM strategies for the loss distribution is also carried out in this paper. Benchmarking results show that the proposed strategy has effective and superior performance...

  17. Load-deflection characteristics of small-bore insulated-pipe clamps

    International Nuclear Information System (INIS)

    Severud, L.K.; Clark, G.L.

    1981-12-01

    The special insulated clamps used on both FFTF and CRBR piping utilize a Belleville spring arrangement to compensate for pipe thermal expansion. Analysis indicates that this produces a non-linear, directionally sensitive clamp spring rate. Since these spring rates influence the seismic response of a supported piping system, it was deemed necessary to evaluate them further by test. This has been accomplished for the FFTF clamps. A more standard insulated pipe clamp, which does not incorporate Belleville springs to accommodate thermal expansion, was also tested. This type clamp is simple in design, and economically attractive. It may have wide application prospects for use in LMFBR small bore auxiliary piping operating at temperatures below 427 0 C. Load deflection tests were conducted on 2.54 CM and 7.62 CM diameter samples of these commercial clamps

  18. Anticancer potential and mechanism of action of mango ginger (Curcuma amada Roxb.) supercritical CO₂ extract in human glioblastoma cells.

    Science.gov (United States)

    Ramachandran, Cheppail; Lollett, Ivonne V; Escalon, Enrique; Quirin, Karl-Werner; Melnick, Steven J

    2015-04-01

    Mango ginger (Curcuma amada Roxb.) is among the less-investigated species of Curcuma for anticancer properties. We have investigated the anticancer potential and the mechanism of action of a supercritical CO2 extract of mango ginger (CA) in the U-87MG human glioblastoma cell line. CA demonstrated higher cytotoxicity than temozolomide, etoposide, curcumin, and turmeric force with IC50, IC75, and IC90 values of 4.92 μg/mL, 12.87 μg/mL, and 21.30 μg/mL, respectively. Inhibitory concentration values of CA for normal embryonic mouse hypothalamus cell line (mHypoE-N1) is significantly higher than glioblastoma cell line, indicating the specificity of CA against brain tumor cells. CompuSyn analysis indicates that CA acts synergistically with temozolomide and etoposide for the cytotoxicity with combination index values of <1. CA treatment also induces apoptosis in glioblastoma cells in a dose-dependent manner and downregulates genes associated with apoptosis, cell proliferation, telomerase activity, oncogenesis, and drug resistance in glioblastoma cells. © The Author(s) 2014.

  19. Acute Elevated Glucose Promotes Abnormal Action Potential-Induced Ca2+ Transients in Cultured Skeletal Muscle Fibers

    Directory of Open Access Journals (Sweden)

    Erick O. Hernández-Ochoa

    2017-01-01

    Full Text Available A common comorbidity of diabetes is skeletal muscle dysfunction, which leads to compromised physical function. Previous studies of diabetes in skeletal muscle have shown alterations in excitation-contraction coupling (ECC—the sequential link between action potentials (AP, intracellular Ca2+ release, and the contractile machinery. Yet, little is known about the impact of acute elevated glucose on the temporal properties of AP-induced Ca2+ transients and ionic underlying mechanisms that lead to muscle dysfunction. Here, we used high-speed confocal Ca2+ imaging to investigate the temporal properties of AP-induced Ca2+ transients, an intermediate step of ECC, using an acute in cellulo model of uncontrolled hyperglycemia (25 mM, 48 h.. Control and elevated glucose-exposed muscle fibers cultured for five days displayed four distinct patterns of AP-induced Ca2+ transients (phasic, biphasic, phasic-delayed, and phasic-slow decay; most control muscle fibers show phasic AP-induced Ca2+ transients, while most fibers exposed to elevated D-glucose displayed biphasic Ca2+ transients upon single field stimulation. We hypothesize that these changes in the temporal profile of the AP-induced Ca2+ transients are due to changes in the intrinsic excitable properties of the muscle fibers. We propose that these changes accompany early stages of diabetic myopathy.

  20. The taurine transporter substrate guanidinoethyl sulfonate mimics the action of taurine on long-term synaptic potentiation.

    Science.gov (United States)

    Suárez, Luz M; Muñoz, María-Dolores; González, José C; Bustamante, Julián; Del Río, Rafael Martín; Solís, José M

    2016-11-01

    Taurine is especially abundant in rodent brain where it appears to be involved in osmoregulation and synaptic plasticity mechanisms. The demonstration of a physiological role for taurine has been hampered by the difficulty in modifying taurine levels in most tissues, including the brain. We used an experimental strategy to reduce taurine levels, involving treatment with guanidinoethyl sulfonate (GES), a structural analogue of taurine that, among other properties, acts as a competitive inhibitor of taurine transport. GES delivered in the drinking water of rats for 1 month effectively reduced taurine levels in brain structures (hippocampus, cerebellum and cortex) and outside the brain (heart, muscle, kidney, liver and plasma) by between 50 and 80 %, depending on the tissue. This partial taurine depletion did not affect either basal synaptic transmission or the late phase of long-term potentiation (late-LTP) in hippocampal slices. In vivo microdialysis studies in the hippocampus revealed that GES treatment reduced extracellular taurine levels and the magnitude of taurine released in response to the application of either N-methyl-D-aspartate (NMDA) or a hypoosmotic solution, without affecting release mechanisms. Finally, we demonstrated in hippocampal slices that a brief GES application can mimic taurine action on the conversion of a decremental LTP into a perdurable late-LTP, concluding that GES might replace taurine function in some mechanisms such as those implicated in synaptic plasticity.

  1. Establishment of alternative potency test for botulinum toxin type A using compound muscle action potential (CMAP) in rats.

    Science.gov (United States)

    Torii, Yasushi; Goto, Yoshitaka; Nakahira, Shinji; Ginnaga, Akihiro

    2014-11-01

    The biological activity of botulinum toxin type A has been evaluated using the mouse intraperitoneal (ip) LD50 test. This method requires a large number of mice to precisely determine toxin activity, and, as such, poses problems with regard to animal welfare. We previously developed a compound muscle action potential (CMAP) assay using rats as an alternative method to the mouse ip LD50 test. In this study, to evaluate this quantitative method of measuring toxin activity using CMAP, we assessed the parameters necessary for quantitative tests according to ICH Q2 (R1). This assay could be used to evaluate the activity of the toxin, even when inactive toxin was mixed with the sample. To reduce the number of animals needed, this assay was set to measure two samples per animal. Linearity was detected over a range of 0.1-12.8 U/mL, and the measurement range was set at 0.4-6.4 U/mL. The results for accuracy and precision showed low variability. The body weight was selected as a variable factor, but it showed no effect on the CMAP amplitude. In this study, potency tests using the rat CMAP assay of botulinum toxin type A demonstrated that it met the criteria for a quantitative analysis method. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Three-dimensional renal CT angiography for guiding segmental renal artery clamping during laparoscopic partial nephrectomy

    International Nuclear Information System (INIS)

    Xu, Yi; Shao, Pengfei; Zhu, Xiaomei; Lv, Qiang; Liu, Wangyan; Xu, Hai; Zhu, Yinsu; Yang, Guangyu; Tang, Lijun; Yin, Changjun

    2013-01-01

    Aim: To evaluate the effectiveness of three-dimensional (3D) renal computed tomography angiography (CTA) in guiding segmental renal artery clamping during laparoscopic partial nephrectomy (LPN). Materials and methods: Forty-three patients with renal tumours undergoing renal CTA before LPN were retrospectively enrolled in this study. 3D arteriogram reconstructed images were created to identify the renal tumour-supplying arteries. The number and location of these targeted vessels were annotated on 3D images preoperatively and compared with the clamped vessels during LPN. The consistency between target vessels annotated at CTA and clamped arteries at LPN was compared both using a patient-based analysis and vessel-based analysis. The χ 2 test was applied to analyse the influence of tumour size, location, and growth pattern on the number of clamped segmental renal branches. Results: On patient-based analysis, the number of targeted vessels was consistent with the clamped vessels during LPN in 33 of 43 patients. On vessel-based analysis, 56 of 65 target vessels annotated at CTA were clamped during LPN. More segmental renal branches (p = 0.04) were clamped in patients with tumours of larger size. Tumour location and growth pattern had no association with the number of clamped segmental branches during LPN. Conclusion: High-quality CTA images and 3D reconstruction images can detect detailed information of tumour-supplying arteries to renal tumours. 3D renal CTA is an effective way to guide segmental renal artery clamping during LPN

  3. An exploratory investigation of various modes of action and potential adverse outcomes of fluoxetine in marine mussels

    International Nuclear Information System (INIS)

    Franzellitti, Silvia; Buratti, Sara; Capolupo, Marco; Du, Bowen; Haddad, Samuel P.; Chambliss, C. Kevin; Brooks, Bryan W.; Fabbri, Elena

    2014-01-01

    Highlights: • Mode of action (MOA) related endpoints and biomarkers of toxicity were assessed in mussels exposed to fluoxetine (FX). • Significant FX bioaccumulation was observed in tissues of mussels exposed to 30 and 300 ng/L FX. • Alterations of cAMP-related cell signaling were observed in exposed mussels as part of the MOA of FX. • FX reduced the health status of mussels inducing lysosomal effects in digestive gland and antioxidant responses in gills. • The importance of considering additional MOAs and adverse outcome pathways for FX impacts on mussels is highlighted. - Abstract: The present study investigated possible adverse outcome pathways (AOPs) of the antidepressant fluoxetine (FX) in the marine mussel Mytilus galloprovincialis. An evaluation of molecular endpoints involved in modes of action (MOAs) of FX and biomarkers for sub-lethal toxicity were explored in mussels after a 7-day administration of nominal FX concentrations encompassing a range of environmentally relevant values (0.03–300 ng/L). FX bioaccumulated in mussel tissues after treatment with 30 and 300 ng/L FX, resulting in bioconcentration factor (BCF) values ranging from 200 to 800, which were higher than expected based solely on hydrophobic partitioning models. Because FX acts as a selective serotonin (5-HT) re-uptake inhibitor increasing serotonergic neurotransmission at mammalian synapses, cell signaling alterations triggered by 5-HT receptor occupations were assessed. cAMP levels and PKA activities were decreased in digestive gland and mantle/gonads of FX-treated mussels, consistent with an increased occupation of 5-HT1 receptors negatively coupled to the cAMP/PKA pathway. mRNA levels of a ABCB gene encoding the P-glycoprotein were also significantly down-regulated. This membrane transporter acts in detoxification towards xenobiotics and in altering pharmacokinetics of antidepressants; moreover, it is under a cAMP/PKA transcriptional regulation in mussels. Potential stress

  4. An exploratory investigation of various modes of action and potential adverse outcomes of fluoxetine in marine mussels

    Energy Technology Data Exchange (ETDEWEB)

    Franzellitti, Silvia, E-mail: silvia.franzellitti@unibo.it [University of Bologna, Interdepartment Centre for Environmental Science Research, via S. Alberto 163, 48123 Ravenna (Italy); University of Bologna, Department of Biological, Geological, and Environmental Sciences, via Selmi 3, 40100 Bologna (Italy); Buratti, Sara; Capolupo, Marco [University of Bologna, Interdepartment Centre for Environmental Science Research, via S. Alberto 163, 48123 Ravenna (Italy); Du, Bowen; Haddad, Samuel P. [Department of Environmental Science, Baylor University, Waco, TX 76798 (United States); Chambliss, C. Kevin [Department of Chemistry and Biochemistry, Baylor University, Waco, TX 76798 (United States); Brooks, Bryan W. [Department of Environmental Science, Baylor University, Waco, TX 76798 (United States); Fabbri, Elena [University of Bologna, Interdepartment Centre for Environmental Science Research, via S. Alberto 163, 48123 Ravenna (Italy); University of Bologna, Department of Biological, Geological, and Environmental Sciences, via Selmi 3, 40100 Bologna (Italy)

    2014-06-01

    Highlights: • Mode of action (MOA) related endpoints and biomarkers of toxicity were assessed in mussels exposed to fluoxetine (FX). • Significant FX bioaccumulation was observed in tissues of mussels exposed to 30 and 300 ng/L FX. • Alterations of cAMP-related cell signaling were observed in exposed mussels as part of the MOA of FX. • FX reduced the health status of mussels inducing lysosomal effects in digestive gland and antioxidant responses in gills. • The importance of considering additional MOAs and adverse outcome pathways for FX impacts on mussels is highlighted. - Abstract: The present study investigated possible adverse outcome pathways (AOPs) of the antidepressant fluoxetine (FX) in the marine mussel Mytilus galloprovincialis. An evaluation of molecular endpoints involved in modes of action (MOAs) of FX and biomarkers for sub-lethal toxicity were explored in mussels after a 7-day administration of nominal FX concentrations encompassing a range of environmentally relevant values (0.03–300 ng/L). FX bioaccumulated in mussel tissues after treatment with 30 and 300 ng/L FX, resulting in bioconcentration factor (BCF) values ranging from 200 to 800, which were higher than expected based solely on hydrophobic partitioning models. Because FX acts as a selective serotonin (5-HT) re-uptake inhibitor increasing serotonergic neurotransmission at mammalian synapses, cell signaling alterations triggered by 5-HT receptor occupations were assessed. cAMP levels and PKA activities were decreased in digestive gland and mantle/gonads of FX-treated mussels, consistent with an increased occupation of 5-HT1 receptors negatively coupled to the cAMP/PKA pathway. mRNA levels of a ABCB gene encoding the P-glycoprotein were also significantly down-regulated. This membrane transporter acts in detoxification towards xenobiotics and in altering pharmacokinetics of antidepressants; moreover, it is under a cAMP/PKA transcriptional regulation in mussels. Potential stress

  5. pH Dependent Antimicrobial Peptides and Proteins, Their Mechanisms of Action and Potential as Therapeutic Agents

    Directory of Open Access Journals (Sweden)

    Erum Malik

    2016-11-01

    Full Text Available Antimicrobial peptides (AMPs are potent antibiotics of the innate immune system that have been extensively investigated as a potential solution to the global problem of infectious diseases caused by pathogenic microbes. A group of AMPs that are increasingly being reported are those that utilise pH dependent antimicrobial mechanisms, and here we review research into this area. This review shows that these antimicrobial molecules are produced by a diverse spectrum of creatures, including vertebrates and invertebrates, and are primarily cationic, although a number of anionic examples are known. Some of these molecules exhibit high pH optima for their antimicrobial activity but in most cases, these AMPs show activity against microbes that present low pH optima, which reflects the acidic pH generally found at their sites of action, particularly the skin. The modes of action used by these molecules are based on a number of major structure/function relationships, which include metal ion binding, changes to net charge and conformational plasticity, and primarily involve the protonation of histidine, aspartic acid and glutamic acid residues at low pH. The pH dependent activity of pore forming antimicrobial proteins involves mechanisms that generally differ fundamentally to those used by pH dependent AMPs, which can be described by the carpet, toroidal pore and barrel-stave pore models of membrane interaction. A number of pH dependent AMPs and antimicrobial proteins have been developed for medical purposes and have successfully completed clinical trials, including kappacins, LL-37, histatins and lactoferrin, along with a number of their derivatives. Major examples of the therapeutic application of these antimicrobial molecules include wound healing as well as the treatment of multiple cancers and infections due to viruses, bacteria and fungi. In general, these applications involve topical administration, such as the use of mouth washes, cream formulations

  6. Trans-Z-source Neutral Point Clamped inverter

    DEFF Research Database (Denmark)

    Mo, W.; Loh, P. C.; Li, D.

    2012-01-01

    Transformer based Z-source (trans-Z-source) inverters are recently proposed by extending the traditional Z-source inverter with higher buck-boost capability as well as reducing the passive components at the same time. Multi-Level Z-source inverters are single-stage topological solutions used...... for buck-boost energy conversion with all the favourable advantages of multi-level switching retained. This paper presents three-level trans-Z-source Neutral Point Clamped (NPC) inverter topology, which achieves both the advantages of trans-Z-source and three-level NPC inverter configuration. With proper...... modulation scheme, the three-level trans-Z-source inverter can function with minimum of six device commutations per half carrier cycle (same as the traditional buck NPC inverter), while maintaining to produce the designed volt-sec average and inductive voltage boosting at ac output terminals. The designed...

  7. Pulsewidth-modulated 2-source neutral-point-clamped inverter

    DEFF Research Database (Denmark)

    Blaabjerg, Frede; Loh, Poh Chang; Gao, Feng

    2007-01-01

    This paper presents the careful integration of a newly proposed Z-source topological concept to the basic neutral-point-clamped (NPC) inverter topology for designing a three-level inverter with both voltage-buck and voltage-boost capabilities. The designed Z-source NPC inverter uses two unique X......-shaped inductance-capacitance (LC) impedance networks that are connected between two isolated dc input power sources and its inverter circuitry for boosting its AC output voltage. Through the design of an appropriate pulsewidth-modulation (PWM) algorithm, the two impedance networks can be short......-circuited sequentially (without shooting through the inverter full DC link) for implementing the ldquonearest-three-vectorrdquo modulation principle with minimized harmonic distortion and device commutations per half carrier cycle while performing voltage boosting. With only a slight modification to the inverter PWM...

  8. Electrothermally actuated tunable clamped-guided resonant microbeams

    KAUST Repository

    Alcheikh, Nouha

    2017-06-11

    We present simulation and experimental investigation demonstrating active alteration of the resonant and frequency response behavior of resonators by controlling the electrothermal actuation method on their anchors. In-plane clamped-guided arch and straight microbeams resonators are designed and fabricated with V-shaped electrothermal actuators on their anchors. These anchors not only offer various electrothermal actuation options, but also serve as various mechanical stiffness elements that affect the operating resonance frequency of the structures. We have shown that for an arch, the first mode resonance frequency can be increased up to 50% of its initial value. For a straight beam, we have shown that before buckling, the resonance frequency decreases to very low values and after buckling, it increases up to twice of its initial value. These results can be promising for the realization of different wide–range tunable microresonator. The experimental results have been compared to multi-physics finite-element simulations showing good agreement among them.

  9. Electrothermally actuated tunable clamped-guided resonant microbeams

    Science.gov (United States)

    Alcheikh, N.; Hajjaj, A. Z.; Jaber, N.; Younis, M. I.

    2018-01-01

    We present simulation and experimental investigation demonstrating active alteration of the resonant and frequency response behavior of resonators by controlling the electrothermal actuation method on their anchors. In-plane clamped-guided arch and straight microbeams resonators are designed and fabricated with V-shaped electrothermal actuators on their anchors. These anchors not only offer various electrothermal actuation options, but also serve as various mechanical stiffness elements that affect the operating resonance frequency of the structures. We have shown that for an arch, the first mode resonance frequency can be increased up to 50% of its initial value. For a straight beam, we have shown that before buckling, the resonance frequency decreases to very low values and after buckling, it increases up to twice of its initial value. These results can be promising for the realization of different wide-range tunable microresonator. The experimental results have been compared to multi-physics finite-element simulations showing good agreement among them.

  10. From understanding cellular function to novel drug discovery: the role of planar patch-clamp array chip technology

    Directory of Open Access Journals (Sweden)

    Christophe ePy

    2011-10-01

    Full Text Available All excitable cell functions rely upon ion channels that are embedded in their plasma membrane. Perturbations of ion channel structure or function result in pathologies ranging from cardiac dysfunction to neurodegenerative disorders. Consequently, to understand the functions of excitable cells and to remedy their pathophysiology, it is important to understand the ion channel functions under various experimental conditions – including exposure to novel drug targets. Glass pipette patch-clamp is the state of the art technique to monitor the intrinsic and synaptic properties of neurons. However, this technique is labor-intensive and has low data throughput. Planar patch-clamp chips, integrated into automated systems, offer high throughputs but are limited to isolated cells from suspensions, resulting in questionable models of true physiological function, and are unsuitable for studies involving neuronal communication. Multi-electrode arrays (MEA, in contrast, have the ability to monitor network activity by measuring local field potentials from multiple extracellular sites, but specific ion channel activity is challenging to extract from these multiplexed signals. Here we describe a novel planar patch-clamp chip technology that enables the simultaneous high resolution electrophysiological interrogation of individual neurons at multiple sites in synaptically connected neuronal networks, thereby combining the advantages of MEA and patch-clamp techniques. Each neuron can be probed through an aperture that connects to a dedicated subterranean microfluidic channel. Neurons growing in networks are aligned to the apertures by physisorbed or chemisorbed chemical cues. In this review, we describe the design and fabrication process of these chips, the approach to the chemical patterning for cell placement, and present physiological data from cultured neuronal cells.

  11. Effects of mixing technologies on continuous methyl ester production: Comparison of using plug flow, static mixer, and ultrasound clamp

    International Nuclear Information System (INIS)

    Somnuk, Krit; Prasit, Tanongsak; Prateepchaikul, Gumpon

    2017-01-01

    Highlights: • Four types of continuous reactors were compared with methyl ester conversion. • Plug flow, static mixer, ultrasound clamp, SM with ultrasound reactors were tested. • The 16 × 400 W ultrasound clamps were operated at 20 kHz frequency for US reactor. • The US reactor was clearly superior over the other types of continuous reactor. • The US reactor was the most effective alternative with short reactor length. - Abstract: Four types of continuous reactors, namely plug flow reactor (PF), static mixer reactor (SM), ultrasound clamp on tubular reactor (US), and static mixer combined with ultrasound (SM/US) were compared for their purities of methyl ester in biodiesel production from refined palm oil (RPO). The reactor conditions were: KOH 4, 6, 8, 10, and 12 g L −1 , methanol content 20 vol.%, and under 20 L h −1 RPO flow rate at 60 °C temperature. The highest purity of methyl esters: 81.99 wt.% for PF, 95.70 wt.% for SM, 98.98 wt.% for US, and 97.67 wt.% for SM/US, were achieved with 900 mm, 900 mm, 700 mm, and 900 mm reactor lengths respectively, and 12 g L −1 of KOH was used in all cases. The 16 × 400 W ultrasound clamp was operated at 20 kHz frequency, and among short length reactors the US case was more effective than PF, SM, or SM/US. Moreover, ester purity from the US reactor was slightly decreased by the lowest 4 g L −1 KOH. The US reactor was clearly superior over the other types of continuous reactor, and had the potential to reduce KOH consumption by sonochemical effects on the base-catalyzed transesterification reaction.

  12. Fabrication of Si-based planar type patch clamp biosensor using silicon on insulator substrate

    International Nuclear Information System (INIS)

    Zhang, Z.L.; Asano, T.; Uno, H.; Tero, R.; Suzui, M.; Nakao, S.; Kaito, T.; Shibasaki, K.; Tominaga, M.; Utsumi, Y.; Gao, Y.L.; Urisu, T.

    2008-01-01

    The aim of this paper is to fabricate the planar type patch clamp ion-channel biosensor, which is suitable for the high throughput screening, using silicon-on-insulator (SOI) substrate. The micropore with 1.2 μm diameter is formed through the top Si layer and the SiO 2 box layer of the SOI substrate by focused ion beam (FIB). Then the substrate is assembled into the microfluidic circuit. The human embryonic kidney 293 (HEK-293) cell transfected with transient receptor potential vanilloid type 1 (TRPV1) is positioned on the micropore and the whole-cell configuration is formed by the suction. Capsaicin is added to the extracellular solution as a ligand molecule, and the channel current showing the desensitization unique to TRPV1 is measured successfully

  13. The free vibration of free-clamped fluid-coupled coaxial cylindrical shells

    International Nuclear Information System (INIS)

    Tani, Junji; Haiji, Hirohisa

    1986-01-01

    The linear free vibration of free-clamped coaxial cylinders partially filled with incompressible, inviscid liquid in the annular gap is investigated theoretically on the basis of the Donnell-type equations for cylinders and the velocity potential theory for liquid motion. The problem is solved by the modified Galerkin method. The initial axisymmetric deformation of the shell due to the static liquid pressure as well as the boundary condition on the free liquid surface are fully taken into consideration. It is found that the static liquid pressure and the liquid surface condition have a significant effect on the natural frequency, and that the interactive effect of the coaxial cylinders becomes small and the mode shape changes with an increase in the wave number and the annular gap. (author)

  14. Fabrication of Si-based planar type patch clamp biosensor using silicon on insulator substrate

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Z.L.; Asano, T. [Graduate University for Advanced Studies, Myodaiji, Okazaki, 444-8585 (Japan); Uno, H. [Institute for Molecular Science, Myodaiji, Okazaki, 444-8585 (Japan); Tero, R. [Graduate University for Advanced Studies, Myodaiji, Okazaki, 444-8585 (Japan); Institute for Molecular Science, Myodaiji, Okazaki, 444-8585 (Japan); Suzui, M.; Nakao, S. [Institute for Molecular Science, Myodaiji, Okazaki, 444-8585 (Japan); Kaito, T. [SII NanoTechnology Inc., 36-1, Takenoshita, Oyama-cho, Sunto-gun, Shizuoka, 410-1393 (Japan); Shibasaki, K.; Tominaga, M. [Okazaki Institute for Integrative Bioscience, 5-1, Higashiyama, Myodaiji, Okazaki, 444-8787 (Japan); Utsumi, Y. [Laboratory of Advanced Science and Technology for Industry, University of Hyogo, 3-1-2, Koto, Kamigori, Ako-gun, Hyogo, 678-1205 (Japan); Gao, Y.L. [Department of Physics and Astronomy, Rochester University, Rochester, New York 14627 (United States); Urisu, T. [Graduate University for Advanced Studies, Myodaiji, Okazaki, 444-8585 (Japan); Institute for Molecular Science, Myodaiji, Okazaki, 444-8585 (Japan)], E-mail: urisu@ims.ac.jp

    2008-03-03

    The aim of this paper is to fabricate the planar type patch clamp ion-channel biosensor, which is suitable for the high throughput screening, using silicon-on-insulator (SOI) substrate. The micropore with 1.2 {mu}m diameter is formed through the top Si layer and the SiO{sub 2} box layer of the SOI substrate by focused ion beam (FIB). Then the substrate is assembled into the microfluidic circuit. The human embryonic kidney 293 (HEK-293) cell transfected with transient receptor potential vanilloid type 1 (TRPV1) is positioned on the micropore and the whole-cell configuration is formed by the suction. Capsaicin is added to the extracellular solution as a ligand molecule, and the channel current showing the desensitization unique to TRPV1 is measured successfully.

  15. Real-time relationship between PKA biochemical signal network dynamics and increased action potential firing rate in heart pacemaker cells

    Science.gov (United States)

    Yaniv, Yael; Ganesan, Ambhighainath; Yang, Dongmei; Ziman, Bruce D.; Lyashkov, Alexey E.; Levchenko, Andre; Zhang, Jin; Lakatta, Edward G.

    2015-01-01

    cAMP-PKA protein kinase is a key nodal signaling pathway that regulates a wide range of heart pacemaker cell functions. These functions are predicted to be involved in regulation of spontaneous action potential (AP) generation of these cells. Here we investigate if the kinetics and stoichiometry of increase in PKA activity match the increase in AP firing rate in response to β-adrenergic receptor (β-AR) stimulation or phosphodiesterase (PDE) inhibition, that alter the AP firing rate of heart sinoatrial pacemaker cells. In cultured adult rabbit pacemaker cells infected with an adenovirous expressing the FRET sensor AKAR3, the EC50 in response to graded increases in the intensity of β-AR stimulation (by Isoproterenol) the magnitude of the increases in PKA activity and the spontaneous AP firing rate were similar (0.4±0.1nM vs. 0.6±0.15nM, respectively). Moreover, the kinetics (t1/2) of the increases in PKA activity and spontaneous AP firing rate in response to β-AR stimulation or PDE inhibition were tightly linked. We characterized the system rate-limiting biochemical reactions by integrating these experimentally derived data into mechanistic-computational model. Model simulations predicted that phospholamban phosphorylation is a potent target of the increase in PKA activity that links to increase in spontaneous AP firing rate. In summary, the kinetics and stoichiometry of increases in PKA activity in response to a physiological (β-AR stimulation) or pharmacological (PDE inhibitor) stimuli match those of changes in the AP firing rate. Thus Ca2+-cAMP/PKA-dependent phosphorylation limits the rate and magnitude of increase in spontaneous AP firing rate. PMID:26241846

  16. Intraoperative cochlear nerve mapping with the mobile cochlear nerve compound action potential tracer in vestibular schwannoma surgery.

    Science.gov (United States)

    Watanabe, Nobuyuki; Ishii, Takuya; Fujitsu, Kazuhiko; Kaku, Shogo; Ichikawa, Teruo; Miyahara, Kosuke; Okada, Tomu; Tanino, Shin; Uriu, Yasuhiro; Murayama, Yuichi

    2018-05-18

    OBJECTIVE The authors describe the usefulness and limitations of the cochlear nerve compound action potential (CNAP) mobile tracer (MCT) that they developed to aid in cochlear nerve mapping during vestibular schwannoma surgery (VSS) for hearing preservation. METHODS This MCT device requires no more than 2 seconds for stable placement on the nerve to obtain the CNAP and thus is able to trace the cochlear nerve instantaneously. Simultaneous bipolar and monopolar recording is possible. The authors present the outcomes of 18 consecutive patients who underwent preoperative useful hearing (defined as class I or II of the Gardner-Robertson classification system) and underwent hearing-preservation VSS with the use of the MCT. Mapping was considered successful when it was possible to detect and trace the cochlear nerve. RESULTS Mapping of the cochlear nerve was successful in 13 of 18 patients (72.2%), and useful hearing was preserved in 11 patients (61.1%). Among 8 patients with large tumors (Koos grade 3 or 4), the rate of successful mapping was 62.5% (5 patients). The rate of hearing preservation in patients with large tumors was 50% (4 patients). CONCLUSIONS In addition to microsurgical presumption of the arrangement of each nerve, frequent probing on and around an unidentified nerve and comparison of each waveform are advisable with the use of both more sensitive monopolar and more location-specific bipolar MCT. MCT proved to be useful in cochlear nerve mapping and may consequently be helpful in hearing preservation. The authors discuss some limitations and problems with this device.

  17. Action potential-evoked calcium release is impaired in single skeletal muscle fibers from heart failure patients.

    Directory of Open Access Journals (Sweden)

    Marino DiFranco

    Full Text Available Exercise intolerance in chronic heart failure (HF has been attributed to abnormalities of the skeletal muscles. Muscle function depends on intact excitation-contraction coupling (ECC, but ECC studies in HF models have been inconclusive, due to deficiencies in the animal models and tools used to measure calcium (Ca2+ release, mandating investigations in skeletal muscle from HF patients. The purpose of this study was to test the hypothesis that Ca2+ release is significantly impaired in the skeletal muscle of HF patients in whom exercise capacity is severely diminished compared to age-matched healthy volunteers.Using state-of-the-art electrophysiological and optical techniques in single muscle fibers from biopsies of the locomotive vastus lateralis muscle, we measured the action potential (AP-evoked Ca2+ release in 4 HF patients and 4 age-matched healthy controls. The mean peak Ca2+ release flux in fibers obtained from HF patients (10±1.2 µM/ms was markedly (2.6-fold and significantly (p<0.05 smaller than in fibers from healthy volunteers (28±3.3 µM/ms. This impairment in AP-evoked Ca2+ release was ubiquitous and was not explained by differences in the excitability mechanisms since single APs were indistinguishable between HF patients and healthy volunteers.These findings prove the feasibility of performing electrophysiological experiments in single fibers from human skeletal muscle, and offer a new approach for investigations of myopathies due to HF and other diseases. Importantly, we have demonstrated that one step in the ECC process, AP-evoked Ca2+ release, is impaired in single muscle fibers in HF patients.

  18. Role of glycolysis in maintenance of the action potential duration and contractile activity in isolated perfused rat heart.

    Science.gov (United States)

    Opie, L H; Tuschmidt, R; Bricknell, O; Girardier, L

    1980-01-01

    1. Changing substrates from glucose to pyruvate in paced isolated rat hearts, perfused by the Langendorff technique at 65 cm H2O with a Krebs-Henseleit bicarbonate buffer, produced effects which are opposite to those of ouabain treatment: negative inotropy, decreased work efficiency, hyperpolarization, increased maximum rate of rise and amplitude of the action potential, increased conduction velocity. 2. All the effects resulting from perfusion with pyruvate can be reversed by adding ouabain at a concentration of 100 microM. 3. The correlation between various tissue metabolises and change in contractile force (delta F), rate of tension development [maximum + (dF/dt)] and rate of relaxation [maximum -(dF/dt)] was studied by multiple linear regression. No significant correlation was found with either glycogen content and tissue lactate or with cAMP and cGMP. A weak negative correlation was found with ATP and phosphocreatine. The strongest correlation was found 76 to 807 nM/g in passing from glucose- to pyruvate-containing perfusion solution. 4. In vitro tests performed with a solution containing high energy phosphates and magnesium at concentrations equal to their calculated values in the cytosol (pH 7.0) showed that a significant negative correlation exists between citrate concentration (range: 1 and 1500 M) and free calcium concentration in the micromole range. 5. It is concluded that the effects of pyruvate (non glucose substrate) perfusion could be mediated by a decrease in cytosolic-free calcium resulting from an increase in intracellular citrate. The observation that all these effects can be reversed by ouabain is taken as a circumstantial evidence of a common mechanism.

  19. Role of suppression of the inward rectifier current in terminal action potential repolarization in the failing heart.

    Science.gov (United States)

    Klein, Michael G; Shou, Matie; Stohlman, Jayna; Solhjoo, Soroosh; Haigney, Myles; Tidwell, Richard R; Goldstein, Robert E; Flagg, Thomas P; Haigney, Mark C

    2017-08-01

    The failing heart exhibits an increased arrhythmia susceptibility that is often attributed to action potential (AP) prolongation due to significant ion channel remodeling. The inwardly rectifying K + current (I K1 ) has been reported to be reduced, but its contribution to shaping the AP waveform and cell excitability in the failing heart remains unclear. The purpose of this study was to define the effect of I K1 suppression on the cardiac AP and excitability in the normal and failing hearts. We used electrophysiological and pharmacological approaches to investigate I K1 function in a swine tachy-pacing model of heart failure (HF). Terminal repolarization of the AP (TRAP; the time constant of the exponential fit to terminal repolarization) was markedly prolonged in both myocytes and arterially perfused wedges from animals with HF. TRAP was increased by 54.1% in HF myocytes (P < .001) and 26.2% in HF wedges (P = .014). The increase in TRAP was recapitulated by the potent and specific I K1 inhibitor, PA-6 (pentamidine analog 6), indicating that I K1 is the primary determinant of the final phase of repolarization. Moreover, we find that I K1 suppression reduced the ratio of effective refractory period to AP duration at 90% of repolarization, permitting re-excitation before full repolarization, reduction of AP upstroke velocity, and likely promotion of slow conduction. Using an objective measure of terminal repolarization, we conclude that I K1 is the major determinant of the terminal repolarization time course. Moreover, suppression of I K1 prolongs repolarization and reduces postrepolarization refractoriness without marked effects on the overall AP duration. Collectively, these findings demonstrate how I K1 suppression may contribute to arrhythmogenesis in the failing heart. Published by Elsevier Inc.

  20. Effect of mental challenge induced by movie clips on action potential duration in normal human subjects independent of heart rate.

    Science.gov (United States)

    Child, Nicholas; Hanson, Ben; Bishop, Martin; Rinaldi, Christopher A; Bostock, Julian; Western, David; Cooklin, Michael; O'Neil, Mark; Wright, Matthew; Razavi, Reza; Gill, Jaswinder; Taggart, Peter

    2014-06-01

    Mental stress and emotion have long been associated with ventricular arrhythmias and sudden death in animal models and humans. The effect of mental challenge on ventricular action potential duration (APD) in conscious healthy humans has not been reported. Activation recovery intervals measured from unipolar electrograms as a surrogate for APD (n=19) were recorded from right and left ventricular endocardium during steady-state pacing, whilst subjects watched an emotionally charged film clip. To assess the possible modulating role of altered respiration on APD, the subjects then repeated the same breathing pattern they had during the stress, but without the movie clip. Hemodynamic parameters (mean, systolic, and diastolic blood pressure, and rate of pressure increase) and respiration rate increased during the stressful part of the film clip (P=0.001). APD decreased during the stressful parts of the film clip, for example, for global right ventricular activation recovery interval at end of film clip 193.8 ms (SD, 14) versus 198.0 ms (SD, 13) during the matched breathing control (end film left ventricle 199.8 ms [SD, 16] versus control 201.6 ms [SD, 15]; P=0.004). Respiration rate increased during the stressful part of the film clip (by 2 breaths per minute) and was well matched in the respective control period without any hemodynamic or activation recovery interval changes. Our results document for the first time direct recordings of the effect of a mental challenge protocol on ventricular APD in conscious humans. The effect of mental challenge on APD was not secondary to emotionally induced altered respiration or heart rate. © 2014 American Heart Association, Inc.

  1. Evaluation of Nystatin Containing Chitosan Hydrogels as Potential Dual Action Bio-Active Restorative Materials: in Vitro Approach

    Directory of Open Access Journals (Sweden)

    V. Tamara Perchyonok

    2014-11-01

    Full Text Available Healing is a specific biological process related to the general phenomenon of growth and tissue regeneration and is a process generally affected by several systemic conditions or as detrimental side-effects of chemotherapy- and radiotherapy-induced inflammation of the oral mucosa. The objectives of this study is to evaluate the novel chitosan based functional drug delivery systems, which can be successfully incorporated into “dual action bioactive restorative materials”, capable of inducing in vitro improved wound healing prototype and containing an antibiotic, such as nystatin, krill oil as an antioxidant and hydroxyapatite as a molecular bone scaffold, which is naturally present in bone and is reported to be successfully used in promoting bone integration when implanted as well as promoting healing. The hydrogels were prepared using a protocol as previously reported by us. The physico-chemical features, including surface morphology (SEM, release behaviors, stability of the therapeutic agent-antioxidant-chitosan, were measured and compared to the earlier reported chitosan-antioxidant containing hydrogels. Structural investigations of the reactive surface of the hydrogel are reported. Release of nystatin was investigated for all newly prepared hydrogels. Bio-adhesive studies were performed in order to assess the suitability of these designer materials. Free radical defense capacity of the biomaterials was evaluated using established in vitro model. The bio-adhesive capacity of the materials in the in vitro system was tested and quantified. It was found that the favorable synergistic effect of free radical built-in defense mechanism of the new functional materials increased sustainable bio-adhesion and therefore acted as a functional multi-dimensional restorative material with potential application in wound healing in vitro.

  2. Clamped end conditions and cross section deformation in the finite element absolute nodal coordinate formulation

    International Nuclear Information System (INIS)

    Hussein, Bassam A.; Weed, David; Shabana, Ahmed A.

    2009-01-01

    In the finite element absolute nodal coordinate formulation (ANCF), the elimination of the relative translations and rotations at a point does not necessarily define a fully clamped joint, particularly in the case of fully parameterized ANCF finite elements that allow for the deformation of the cross section. In this investigation, the formulations and results of two different sets of clamped end conditions that define two different joints are compared. The first joint, called the partially clamped joint, eliminates only the translations and rotations at a point on the cross section. The second joint, called the fully clamped joint, eliminates all the translation, rotation and deformation degrees of freedom at a point on the cross section. The kinematic equations that define the partially and fully clamped joints are developed, and the dynamic equations used in the comparative numerical study presented in this paper are shown. As discussed in this investigation, the fully clamped joint does not allow for the deformation of the cross section at the joint node since the gradient vectors remain orthogonal unit vectors. The partially clamped joint, on the other hand, allows for the deformation of the cross section. Nanson's formula is used as a measure of the deformation of the cross section in the case of the partially clamped joint. A very flexible pendulum that has a rigid body attached to its free end is used to compare the results of the partially and fully clamped joints. The numerical results obtained using this very flexible pendulum example show that, while the type of joint (partially or fully clamped) does not significantly affect the gross reference motion of the system, there are fundamental differences between the two joints since the partially clamped joint allows for the cross section deformations at the joint node

  3. Normative findings of electrically evoked compound action potential measurements using the neural response telemetry of the Nucleus CI24M cochlear implant system.

    NARCIS (Netherlands)

    Cafarelli-Dees, D.; Dillier, N.; Lai, W.K.; Wallenberg, E. von; Dijk, B. van; Akdas, F.; Aksit, M.; Batman, C.; Beynon, A.J.; Burdo, S.; Chanal, J.M.; Collet, L.; Conway, M.; Coudert, C.; Craddock, L.; Cullington, H.; Deggouj, N.; Fraysse, B.; Grabel, S.; Kiefer, J.; Kiss, J.G.; Lenarz, T.; Mair, A.; Maune, S.; Muller-Deile, J.; Piron, J.P.; Razza, S.; Tasche, C.; Thai-Van, H.; Toth, F.; Truy, E.; Uziel, A.; Smoorenburg, G.F.

    2005-01-01

    One hundred and forty-seven adult recipients of the Nucleus 24 cochlear implant system, from 13 different European countries, were tested using neural response telemetry to measure the electrically evoked compound action potential (ECAP), according to a standardised postoperative measurement

  4. Subtype-specific promoter-driven action potential imaging for precise disease modelling and drug testing in hiPSC-derived cardiomyocytes

    NARCIS (Netherlands)

    Chen, Zhifen; Xian, Wenying; Bellin, Milena; Dorn, Tatjana; Tian, Qinghai; Goedel, Alexander; Dreizehnter, Lisa; Schneider, Christine M.; Ward-van Oostwaard, Dorien; Ng, Judy King Man; Hinkel, Rabea; Pane, Luna Simona; Mummery, Christine L.; Lipp, Peter; Moretti, Alessandra; Laugwitz, Karl-Ludwig; Sinnecker, Daniel

    2016-01-01

    AIMS: Cardiomyocytes (CMs) generated from human induced pluripotent stem cells (hiPSCs) are increasingly used in disease modelling and drug evaluation. However, they are typically a heterogeneous mix of ventricular-, atrial-, and nodal-like cells based on action potentials (APs) and gene expression.

  5. High frequency action potential bursts (≥ 100 Hz) in L2/3 and L5B thick tufted neurons in anaesthetized and awake rat primary somatosensory cortex

    NARCIS (Netherlands)

    C.P.J. de Kock (Christiaan); B. Sakmann (Bert)

    2008-01-01

    textabstractHigh frequency (≥ 100 Hz) bursts of action potentials (APs) generated by neocortical neurons are thought to increase information content and, through back-propagation, to influence synaptic integration and efficacy in distal dendritic compartments. It was recently shown in acute slice

  6. Modeling of SVM Diode Clamping Three-Level Inverter Connected to Grid

    DEFF Research Database (Denmark)

    Guo, Yougui; Zeng, Ping; Zhu, Jieqiong

    2011-01-01

    PLECS is used to model the diode clamping three-level inverter connected to grid and good results are obtained. First the output voltage SVM is described for diode clamping three-level inverter with loads connected to Y. Then the output voltage SVM of diode clamping three-level inverter is simply...... analyzed with loads connected to △. But it will be further researched in the future. Third, PLECS is briefly introduced. Fourth, the modeling of diode clamping three-level inverter is briefly presented with PLECS. Finally, a series of simulations are carried out. The simulation results tell us PLECS...... is very powerful tool to real power circuits and it is very easy to simulate them. They have also verified that SVM control strategy is feasible to control the diode clamping three-level inverter....

  7. Identification of Glycyrrhiza as the rikkunshito constituent with the highest antagonistic potential on heterologously expressed 5HT3A receptors due to the action of flavonoids

    Directory of Open Access Journals (Sweden)

    Robin eHerbrechter

    2015-07-01

    Full Text Available The traditional Japanese phytomedicine rikkunshito is traditionally used for the treatment of gastrointestinal motility disorders, cachexia and nausea. These effects indicate 5-HT3 receptor antagonism, due to the involvement of these receptors in such pathophysiological processes. E.g. setrons, specific 5-HT3 receptor antagonists are the strongest antiemetics, developed so far. Therefore, the antagonistic effects of the eight rikkunshito constituents at heterologously expressed 5-HT3A receptors were analyzed using the two-electrode voltage-clamp technique. The results indicate that tinctures from Aurantii, Ginseng, Zingiberis, Atractylodis and Glycyrrhiza inhibited the 5-HT3A receptor response, whereas the tinctures of Poria cocos, Jujubae and Pinellia exhibited no effect. Surprisingly, the strongest antagonism was found for Glycyrrhiza, whereas the Zingiberis tincture, which is considered to be primarily responsible for the effect of rikkunshito, exhibited the weakest antagonist of 5-HT3A receptors. Rikkunshito contains various vanilloids, ginsenosides and flavonoids, a portion of which show an antagonistic effect on 5-HT3 receptors. A screening of the established ingredients of the active rikkunshito constituents and related substances lead to the identification of new antagonists within the class of flavonoids. The flavonoids (--liquiritigenin, glabridin and licochalcone A from Glycyrrhiza species were found to be the most effective inhibitors of the 5-HT-induced currents in the screening. The flavonoids (--liquiritigenin and hesperetin from Aurantii inhibited the receptor response in a non-competitive manner, whereas glabridin and licochalcone A exhibited a potential competitive antagonism. Furthermore, licochalcone A acts as a partial antagonist of 5-HT3A receptors. Thus, this study reveals new 5-HT3A receptor antagonists with the aid of increasing the comprehension of the complex effects of rikkunshito.

  8. Potential hazards to embryo implantation: A human endometrial in vitro model to identify unwanted antigestagenic actions of chemicals

    International Nuclear Information System (INIS)

    Fischer, L.; Deppert, W.R.; Pfeifer, D.; Stanzel, S.; Weimer, M.; Hanjalic-Beck, A.; Stein, A.; Straßer, M.; Zahradnik, H.P.; Schaefer, W.R.

    2012-01-01

    Embryo implantation is a crucial step in human reproduction and depends on the timely development of a receptive endometrium. The human endometrium is unique among adult tissues due to its dynamic alterations during each menstrual cycle. It hosts the implantation process which is governed by progesterone, whereas 17β-estradiol regulates the preceding proliferation of the endometrium. The receptors for both steroids are targets for drugs and endocrine disrupting chemicals. Chemicals with unwanted antigestagenic actions are potentially hazardous to embryo implantation since many pharmaceutical antiprogestins adversely affect endometrial receptivity. This risk can be addressed by human tissue-specific in vitro assays. As working basis we compiled data on chemicals interacting with the PR. In our experimental work, we developed a flexible in vitro model based on human endometrial Ishikawa cells. Effects of antiprogestin compounds on pre-selected target genes were characterized by sigmoidal concentration–response curves obtained by RT-qPCR. The estrogen sulfotransferase (SULT1E1) was identified as the most responsive target gene by microarray analysis. The agonistic effect of progesterone on SULT1E1 mRNA was concentration-dependently antagonized by RU486 (mifepristone) and ZK137316 and, with lower potency, by 4-nonylphenol, bisphenol A and apigenin. The negative control methyl acetoacetate showed no effect. The effects of progesterone and RU486 were confirmed on the protein level by Western blotting. We demonstrated proof of principle that our Ishikawa model is suitable to study quantitatively effects of antiprogestin-like chemicals on endometrial target genes in comparison to pharmaceutical reference compounds. This test is useful for hazard identification and may contribute to reduce animal studies. -- Highlights: ► We compare progesterone receptor-mediated endometrial effects of chemicals and drugs. ► 4-Nonylphenol, bisphenol A and apigenin exert weak

  9. Potential hazards to embryo implantation: A human endometrial in vitro model to identify unwanted antigestagenic actions of chemicals

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, L.; Deppert, W.R. [Department of Obstetrics and Gynecology, University Hospital Freiburg (Germany); Pfeifer, D. [Department of Hematology and Oncology, University Hospital Freiburg (Germany); Stanzel, S.; Weimer, M. [Department of Biostatistics, German Cancer Research Center, Heidelberg (Germany); Hanjalic-Beck, A.; Stein, A.; Straßer, M.; Zahradnik, H.P. [Department of Obstetrics and Gynecology, University Hospital Freiburg (Germany); Schaefer, W.R., E-mail: wolfgang.schaefer@uniklinik-freiburg.de [Department of Obstetrics and Gynecology, University Hospital Freiburg (Germany)

    2012-05-01

    Embryo implantation is a crucial step in human reproduction and depends on the timely development of a receptive endometrium. The human endometrium is unique among adult tissues due to its dynamic alterations during each menstrual cycle. It hosts the implantation process which is governed by progesterone, whereas 17β-estradiol regulates the preceding proliferation of the endometrium. The receptors for both steroids are targets for drugs and endocrine disrupting chemicals. Chemicals with unwanted antigestagenic actions are potentially hazardous to embryo implantation since many pharmaceutical antiprogestins adversely affect endometrial receptivity. This risk can be addressed by human tissue-specific in vitro assays. As working basis we compiled data on chemicals interacting with the PR. In our experimental work, we developed a flexible in vitro model based on human endometrial Ishikawa cells. Effects of antiprogestin compounds on pre-selected target genes were characterized by sigmoidal concentration–response curves obtained by RT-qPCR. The estrogen sulfotransferase (SULT1E1) was identified as the most responsive target gene by microarray analysis. The agonistic effect of progesterone on SULT1E1 mRNA was concentration-dependently antagonized by RU486 (mifepristone) and ZK137316 and, with lower potency, by 4-nonylphenol, bisphenol A and apigenin. The negative control methyl acetoacetate showed no effect. The effects of progesterone and RU486 were confirmed on the protein level by Western blotting. We demonstrated proof of principle that our Ishikawa model is suitable to study quantitatively effects of antiprogestin-like chemicals on endometrial target genes in comparison to pharmaceutical reference compounds. This test is useful for hazard identification and may contribute to reduce animal studies. -- Highlights: ► We compare progesterone receptor-mediated endometrial effects of chemicals and drugs. ► 4-Nonylphenol, bisphenol A and apigenin exert weak

  10. Detrended fluctuation analysis of compound action potentials re-corded in the cutaneous nerves of diabetic rats

    International Nuclear Information System (INIS)

    Quiroz-González, Salvador; Rodríguez-Torres, Erika Elizabeth; Segura-Alegría, Bertha; Pereira-Venegas, Javier; Lopez-Gomez, Rosa Estela; Jiménez-Estrada, Ismael

    2016-01-01

    Highlights: • Fractal analysis of compound action potentials (CAP) evoked in diabetic nerves. • Diabetic rats showed an increment in the chaotic behavior of CAP responses. • Diabetes provokes impaired transmission of sensory information in rats. - Abstract: The electrophysiological alterations in nerves due to diabetes are classically studied in relation to their instantaneous frequency, conduction velocity and amplitude. However, analysis of amplitude variability may reflect the occurrence of feedback loop mechanisms that adjust the output as a function of its previous activity could indicate fractal dynamics. We assume that a peripheral neuropathy, such as that evoked by diabetes, the inability to maintain a steady flow of sensory information is reflected as a breakdown of the long range power-law correlation of CAP area fluctuation from cutaneous nerves. To test this, we first explored in normal rats whether fluctuations in the trial-to-trial CAP area showed a self-similar behavior or fractal structure by means of detrended fluctuations analysis (DFA), and Poincare plots. In addition, we determine whether such CAP fluctuations varied by diabetes induction. Results showed that CAP area fluctuation of SU nerves evoked in normal rats present a long term correlation and self-similar organization (fractal behavior) from trial to trial stimulation as evidenced by DFA of CAP areas. However, CAPs recorded in diabetic nerves exhibited significant reductions in area, larger duration and increased area variability and different Poincare plots than control nerves. The Hurst exponent value determined with the DFA method from a series of 2000 CAPs evoked in diabetic SU nerves was smaller than in control nerves. It is proposed that in cutaneous nerves of normal rats variability of the CAP area present a long term correlation and self-similar organization (fractal behavior), and reflect the ability to maintain a steady flow of sensory information through cutaneous nerves

  11. A Comparative Study On The Action Potential Simulation (APS Therapy And The Routine Physiotherapy Protocol In Knee Osteoarthritisin Elderly People

    Directory of Open Access Journals (Sweden)

    Abbas Rahimi

    2012-04-01

    Full Text Available Background and Aim: Knee osteoarthritis is the most common cause for which the elderly people refere to physiotherapy outpatient clinics. This study aimed to investigate the effects of the Action Potential Stimulation (APS Therapy and the routine physiotherapy (PT protocol on relieving pain and swelling as well as the duration of the relief period in patients with knee osteoarthritis. Materials and Methods: 69 patients (62 females & 7 males with knee osteoarthritis were recruited in this study. The subjects were divided into two groups including APS Therapy (n=37, mean age: 55±13 years old and the routine PT protocol (n=32, mean age: 61±14 years old groups. A 10-session treatment period was carried out for each group; and their pain and swelling were measured at the first, fifth and tenth sessions and also one-month after the last session (follow up. The swelling was measured using measuring the circumference of the knee on the patella, 5 Cm above and 5 Cm below the patella. The routine PT protocol consisted of hot pack, ultrasound, TENS and exercise; and the APS therapy protocol included hot pack, APS Therapy and the same exercise. During the follow up, 50 out of 61 subjects were called on the phone and any pain changes were recorded.Results: In terms of swelling, the results showed significant reduction just on the patella only in the APS Therapy group (P<0.05. Visual Analogue Pain Scale (VAPS indicated a significant pain reduction in both groups. However, the APS Therapy group showed significantly pain reduction at the end of sessions five, ten and the follow up session (P<0.05. It was also revealed that while routine PT subjects showed no significant pain changes between the tenth and the follow up session, a gradual pain reduction was seen in the APS therapy group during this period (P<0.05. A gradual dosage reduction was recorded only in the APS therapy group, indicating a slight correlation with pain reduction (r=0.4.Conclusion: The

  12. Spatial correlation of action potential duration and diastolic dysfunction in transgenic and drug-induced LQT2 rabbits.

    Science.gov (United States)

    Odening, Katja E; Jung, Bernd A; Lang, Corinna N; Cabrera Lozoya, Rocio; Ziupa, David; Menza, Marius; Relan, Jatin; Franke, Gerlind; Perez Feliz, Stefanie; Koren, Gideon; Zehender, Manfred; Bode, Christoph; Brunner, Michael; Sermesant, Maxime; Föll, Daniela

    2013-10-01

    Enhanced dispersion of action potential duration (APD) is a major contributor to long QT syndrome (LQTS)-related arrhythmias. To investigate spatial correlations of regional heterogeneities in cardiac repolarization and mechanical function in LQTS. Female transgenic LQTS type 2 (LQT2; n = 11) and wild-type littermate control (LMC) rabbits (n = 9 without E4031 and n = 10 with E4031) were subjected to phase contrast magnetic resonance imaging to assess regional myocardial velocities. In the same rabbits' hearts, monophasic APDs were assessed in corresponding segments. In LQT2 and E4031-treated rabbits, APD was longer in all left ventricular segments (P < .01) and APD dispersion was greater than that in LMC rabbits (P < .01). In diastole, peak radial velocities (Vr) were reduced in LQT2 and E4031-treated compared to LMC rabbits in LV base and mid (LQT2: -3.36 ± 0.4 cm/s, P < .01; E4031-treated: -3.24 ± 0.6 cm/s, P < .0001; LMC: -4.42 ± 0.5 cm/s), indicating an impaired diastolic function. Regionally heterogeneous diastolic Vr correlated with APD (LQT2: correlation coefficient [CC] 0.38, P = .01; E4031-treated: CC 0.42, P < .05). Time-to-diastolic peak Vr were prolonged in LQT2 rabbits (LQT2: 196.8 ± 2.9 ms, P < .001; E4031-treated: 199.5 ± 2.2 ms, P < .0001, LMC 183.1 ± 1.5), indicating a prolonged contraction duration. Moreover, in transgenic LQT2 rabbits, diastolic time-to-diastolic peak Vr correlated with APD (CC 0.47, P = .001). In systole, peak Vr were reduced in LQT2 and E4031-treated rabbits (P < .01) but longitudinal velocities or ejection fraction did not differ. Finally, random forest machine learning algorithms enabled a differentiation between LQT2, E4031-treated, and LMC rabbits solely based on "mechanical" magnetic resonance imaging data. The prolongation of APD led to impaired diastolic and systolic function in transgenic and drug-induced LQT2 rabbits. APD correlated with regional diastolic dysfunction, indicating that LQTS is not purely an

  13. Determination of thermodynamic potentials and the aggregation number for micelles with the mass-action model by isothermal titration calorimetry

    DEFF Research Database (Denmark)

    Olesen, Niels Erik; Westh, Peter; Holm, René

    2015-01-01

    of micelles with ITC were compared to a mass-action model (MAM) of reaction type: n⋅S⇌Mn. This analysis can provide guidelines for future ITC studies of systems behaving in accordance with this model such as micelles and proteins that undergo self-association to oligomers. Micelles with small aggregation...

  14. Different methods of hilar clamping during partial nephrectomy: Impact on renal function.

    Science.gov (United States)

    Lee, Jeong Woo; Kim, Hwanik; Choo, Minsoo; Park, Yong Hyun; Ku, Ja Hyeon; Kim, Hyeon Hoe; Kwak, Cheol

    2014-03-01

    To evaluate the impact of different hilar clamping methods on changes in renal function after partial nephrectomy. We analyzed the clinical data of 369 patients who underwent partial nephrectomy for a single renal tumor of size ≤4.0 cm and a normal contralateral kidney. Patients were separated into three groups depending on hilar clamping method: non-clamping, cold ischemia and warm ischemia. Estimated glomerular filtration rate was examined at preoperative, nadir and 1 year postoperatively. Percent change in estimated glomerular filtration rate was used as the parameter to assess the renal functional outcome. Percent change in nadir estimated glomerular filtration rate in the non-clamping group was significantly less compared with the cold ischemia and warm ischemia groups (P hilar clamping (both warm ischemia and cold ischemia) were significantly associated with percent change in nadir estimated glomerular filtration rate, but not in 1-year estimated glomerular filtration rate. Non-clamping partial nephrectomy results in a lower percent change in nadir estimated glomerular filtration rate, whereas it carries an estimated glomerular filtration rate change at 1 year that is similar to partial nephrectomy with cold ischemia and warm ischemia. Cold ischemia and warm ischemia provide a similar effect on renal function. Therefore, when hilar clamping is required, minimization of ischemia time is necessary. © 2013 The Japanese Urological Association.

  15. Dynamic assembly of Hda and the sliding clamp in the regulation of replication licensing.

    Science.gov (United States)

    Kim, Jin S; Nanfara, Michael T; Chodavarapu, Sundari; Jin, Kyeong S; Babu, Vignesh M P; Ghazy, Mohamed A; Chung, Scisung; Kaguni, Jon M; Sutton, Mark D; Cho, Yunje

    2017-04-20

    Regulatory inactivation of DnaA (RIDA) is one of the major regulatory mechanisms of prokaryotic replication licensing. In RIDA, the Hda-sliding clamp complex loaded onto DNA directly interacts with adenosine triphosphate (ATP)-bound DnaA and stimulates the hydrolysis of ATP to inactivate DnaA. A prediction is that the activity of Hda is tightly controlled to ensure that replication initiation occurs only once per cell cycle. Here, we determined the crystal structure of the Hda-β clamp complex. This complex contains two pairs of Hda dimers sandwiched between two β clamp rings to form an octamer that is stabilized by three discrete interfaces. Two separate surfaces of Hda make contact with the β clamp, which is essential for Hda function in RIDA. The third interface between Hda monomers occludes the active site arginine finger, blocking its access to DnaA. Taken together, our structural and mutational analyses of the Hda-β clamp complex indicate that the interaction of the β clamp with Hda controls the ability of Hda to interact with DnaA. In the octameric Hda-β clamp complex, the inability of Hda to interact with DnaA is a novel mechanism that may regulate Hda function. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  16. Analysis and Experiments on Sea Load and Fastened Mechanics on Pipe Clamps

    Directory of Open Access Journals (Sweden)

    Wang Zhuo

    2017-08-01

    Full Text Available When an offshore oil field completed and put into production, new subsea pipelines and the new cable need to be established. Cable protection pipe clamp is used to fix cable protection pipe on the jacket. In order to avoid the problem of traditional steel structure clamp splice, counterpoint, fastening difficulty when installed cable protection pipe under water, reduce the risk and workload of under water, This paper develop a new type of portable connecting riser clamp -“backpack clamp” which solve the riser cable protection pipe difficult underwater installation problem. The main structure of backpack clamp used three valves type structure. The load characteristic of a clamping device was determined by the Morison equation which was a classical theory. Clamp device underwater mechanics analysis model was established. The minimum tension pre-tightening force was determined. The results show that the strength of the base meets the requirements after strength analysis with finite element analysis method, stability and strength experiments, which means the clamp based on resin matrix composite is feasible.

  17. A missing factor in chip-based patch clamp assay: gigaseal

    International Nuclear Information System (INIS)

    Ong, W-L; Yobas, L; Ong, W-Y

    2006-01-01

    The 'gold' standard in the study of ionic currents across biological membranes is the Patch Clamp method. However, this is a slow, labor and skill intensive process. High throughput patch clamp devices are mainly chip-based. A major challenge in these miniaturized devices is the low rate of 'Gigaseal' formation which is critical in the study of Single Channel effect. In a conventional patch clamp, a pipette moves and patches a fixed cell (cell-adhered patch) which is grown on the bottom of a Petri dish. In the chip-based case, the cells are in suspension and move towards the fixed patch clamp sites (cell-suspended patch). In this study, using the proven conventional patch clamp setup, we investigated the effect of the differences in the cell configurations between the convention patch clamp and cell-based patch clamp. It is shown that adhered cells (as used in the conventional setup) have a much higher rate of gigaseal formation as compared to the cells in suspension (as used in chip-based devices). We postulate that the arrangement of the cytoskeleton within the cell plays a major part in the formation of the gigaseal

  18. A self-strain feedback tuning-fork-shaped ionic polymer metal composite clamping actuator with soft matter elasticity-detecting capability for biomedical applications.

    Science.gov (United States)

    Feng, Guo-Hua; Huang, Wei-Lun

    2014-12-01

    This paper presents a smart tuning-fork-shaped ionic polymer metal composite (IPMC) clamping actuator for biomedical applications. The two fingers of the actuator, which perform the clamping motion, can be electrically controlled through a unique electrode design on the IPMC material. The generated displacement or strain of the fingers can be sensed using an integrated soft strain-gage sensor. The IPMC actuator and associated soft strain gage were fabricated using a micromachining technique. A 13.5×4×2 mm(3) actuator was shaped from Nafion solution and a selectively grown metal electrode formed the active region. The strain gage consisted of patterned copper foil and polyethylene as a substrate. The relationship between the strain gage voltage output and the displacement at the front end of the actuator's fingers was characterized. The equivalent Young's modulus, 13.65 MPa, of the soft-strain-gage-integrated IPMC finger was analyzed. The produced clamping force exhibited a linear increasing rate of 1.07 mN/s, based on a dc driving voltage of 7 V. Using the developed actuator to clamp soft matter and simultaneously acquire its Young's modulus was achieved. This demonstrated the feasibility of the palpation function and the potential use of the actuator in minimally invasive surgery. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Impaired action potential initiation in GABAergic interneurons causes hyperexcitable networks in an epileptic mouse model carrying a human Na(V)1.1 mutation.

    Science.gov (United States)

    Hedrich, Ulrike B S; Liautard, Camille; Kirschenbaum, Daniel; Pofahl, Martin; Lavigne, Jennifer; Liu, Yuanyuan; Theiss, Stephan; Slotta, Johannes; Escayg, Andrew; Dihné, Marcel; Beck, Heinz; Mantegazza, Massimo; Lerche, Holger

    2014-11-05

    Mutations in SCN1A and other ion channel genes can cause different epileptic phenotypes, but the precise mechanisms underlying the development of hyperexcitable networks are largely unknown. Here, we present a multisystem analysis of an SCN1A mouse model carrying the NaV1.1-R1648H mutation, which causes febrile seizures and epilepsy in humans. We found a ubiquitous hypoexcitability of interneurons in thalamus, cortex, and hippocampus, without detectable changes in excitatory neurons. Interestingly, somatic Na(+) channels in interneurons and persistent Na(+) currents were not significantly changed. Instead, the key mechanism of interneuron dysfunction was a deficit of action potential initiation at the axon initial segment that was identified by analyzing action potential firing. This deficit increased with the duration of firing periods, suggesting that increased slow inactivation, as recorded for recombinant mutated channels, could play an important role. The deficit in interneuron firing caused reduced action potential-driven inhibition of excitatory neurons as revealed by less frequent spontaneous but not miniature IPSCs. Multiple approaches indicated increased spontaneous thalamocortical and hippocampal network activity in mutant mice, as follows: (1) more synchronous and higher-frequency firing was recorded in primary neuronal cultures plated on multielectrode arrays; (2) thalamocortical slices examined by field potential recordings revealed spontaneous activities and pathological high-frequency oscillations; and (3) multineuron Ca(2+) imaging in hippocampal slices showed increased spontaneous neuronal activity. Thus, an interneuron-specific generalized defect in action potential initiation causes multisystem disinhibition and network hyperexcitability, which can well explain the occurrence of seizures in the studied mouse model and in patients carrying this mutation. Copyright © 2014 the authors 0270-6474/14/3414874-16$15.00/0.

  20. Analysis of the role of PCNA-DNA contacts during clamp loading

    Directory of Open Access Journals (Sweden)

    Goedken Eric R

    2010-01-01

    Full Text Available Abstract Background Sliding clamps, such as Proliferating Cell Nuclear Antigen (PCNA in eukaryotes, are ring-shaped protein complexes that encircle DNA and enable highly processive DNA replication by serving as docking sites for DNA polymerases. In an ATP-dependent reaction, clamp loader complexes, such as the Replication Factor-C (RFC complex in eukaryotes, open the clamp and load it around primer-template DNA. Results We built a model of RFC bound to PCNA and DNA based on existing crystal structures of clamp loaders. This model suggests that DNA would enter the clamp at an angle during clamp loading, thereby interacting with positively charged residues in the center of PCNA. We show that simultaneous mutation of Lys 20, Lys 77, Arg 80, and Arg 149, which interact with DNA in the RFC-PCNA-DNA model, compromises the ability of yeast PCNA to stimulate the DNA-dependent ATPase activity of RFC when the DNA is long enough to extend through the clamp. Fluorescence anisotropy binding experiments show that the inability of the mutant clamp proteins to stimulate RFC ATPase activity is likely caused by reduction in the affinity of the RFC-PCNA complex for DNA. We obtained several crystal forms of yeast PCNA-DNA complexes, measuring X-ray diffraction data to 3.0 Å resolution for one such complex. The resulting electron density maps show that DNA is bound in a tilted orientation relative to PCNA, but makes different contacts than those implicated in clamp loading. Because of apparent partial disorder in the DNA, we restricted refinement of the DNA to a rigid body model. This result contrasts with previous analysis of a bacterial clamp bound to DNA, where the DNA was well resolved. Conclusion Mutational analysis of PCNA suggests that positively charged residues in the center of the clamp create a binding surface that makes contact with DNA. Disruption of this positive surface, which had not previously been implicated in clamp loading function, reduces RFC

  1. Investigation on the Behavior of the Jointing Clamps to the Simulated Environmental - LOCA

    International Nuclear Information System (INIS)

    Ivan, P.; Segarceanu, D.; Geambasu, C.

    2002-01-01

    The paper presents the main aspect concerning the electric parameter variation of jointing clamps operating under specific environmental conditions determinate by pressure, temperature and humidity. The testing of jointing clamps capability to meet and exceed the required performances all along its operating life implies the performing of LOCA simulation conditions while the jointing clamps is bright in a relatively short time under conditions equivalent to those at the end of its service life. The paper describes ageing and measurement techni