article{ceee0ce3-7cdb-426b-8c17-2f62ad33a172, abstract = {,p,AIMS: To evaluate the usefulness of the signed value of monophasic action potential duration difference in analysing the cause of dispersion of ventricular repolarization.,/p,,p,METHODS AND RESULTS: Monophasic action potentials were simultaneously recorded from the right ventricular apex and outflow tract during programmed stimulation in 36 patients with ventricular arrhythmias. The time difference between the ends of repolarization on the two monophasic action potentials was used as a measure of the dispersion of ventricular repolarization, and the signed value of the monophasic action potential duration difference was used to specify the contributions of the activation time difference and the monophasic action potential duration difference to the dispersion of ventricular repolarization. During right ventricular pacing, single and double programmed stimulation and at the induction of ventricular arrhythmias, the dispersion of ...
Myocardial ischemia-reperfusion (IR) injury represents a constellation of pathological processes that occur when ischemic myocardium experiences a restoration of perfusion. Reentrant arrhythmias, which represent a particularly lethal manifestation of IR injury, can result when ischemic tissue exhibits decreased excitability and/or changes of action potential duration (APD), conditions that precipitate unidirectional conduction block. Many of the cellular components that are involved with IR injury are modulated by pH and/or phosphometabolites such as ATP and phosphocreatine (PCr), all of which can be manipulated in vivo and potentially in the clinical setting. Using a mathematical model of the cardiomyocyte that we previously developed to study ischemia and reperfusion, we performed a series of simulations with the aim of determining whether pH- or phosphometabolite-related processes play a more significant role in generating changes in excitability and action potential morphology that are associated
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TY - JOUR. T1 - Multi-neuron action potentials recorded with tetrode are not instantaneous mixtures of single neuronal action potentials.. AU - Shiraishi, Yasushi. AU - Katayama, Norihiro. AU - Takahashi, Tetsuya. AU - Karashima, Akihiro. AU - Nakao, Mitsuyuki. PY - 2009. Y1 - 2009. N2 - Multiunit recording with multi-site electrodes in the brain has been widely used in neuroscience studies. After the data recording, neuronal spikes should be sorted according to the pattern of spike waveforms. For the spike sorting, independent component analysis (ICA) has recently been used because ICA has potential for resolving the problem to separate the overlapped multiple neuronal spikes. However the performance of spike sorting by using ICA has not been examined in detail. In this study, we quantitatively evaluate the performance of ICA-based spike sorting method by using simulated multiunit signals. The simulated multiunit signal is constructed by compositing real extracellular action potentials recorded ...
Home , Papers , TREK-1 and TRAAK Are Principal K Channels at the Nodes of Ranvier for Rapid Action Potential Conduction on Mammalian Myelinated Afferent Nerves. ...
The combination of the ATCHI stain and microelectrode impalements has shown that the distribution of the RBB and Purkinje fibers of the mouse conduction system is, in general, similar to that reported in other species.14,15 However, in the mouse strain investigated (Swiss Webster), we found that the RBB was, very frequently, intimately associated with the septal artery in the right ventricle and could be visualized under bright field as white fibers running along the artery in base to apex direction. Our investigation provides the first available data on the action potential properties of the murine His-Purkinje system.. Several of the electrophysiological characteristics presented in this study are consistent with data from Purkinje cells from other species.15,32 In one of these studies, action potential properties of Purkinje cells were profiled in cow, sheep, and canine.32 The freshly isolated cells had a maximum diastolic potential of −70 and −85 mV, upstroke velocity of 150 to 750 V/s, ...
Antibodies for proteins involved in positive regulation of voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization pathways, according to their Panther/Gene Ontology Classification
Fingerprint Dive into the research topics of Selective Effects of Potassium Elevations on Glutamate Signaling and Action Potential Conduction in Hippocampus. Together they form a unique fingerprint. ...
The regulation of a K(+) current activating during oscillatory electrical activity (I(K,slow)) in an insulin-releasing beta-cell was studied by applying the perforated patch whole-cell technique to intact mouse pancreatic islets. The resting whole-cell conductance in the presence of 10 mM glucose amounted to 1.3 nS, which rose by 50 % during a series of 26 simulated action potentials. Application of the K(ATP)-channel blocker tolbutamide produced uninterrupted action potential firing and reduced I(K,slow) by approximately 50 %. Increasing glucose from 15 to 30 mM, which likewise converted oscillatory electrical activity into continuous action potential firing, reduced I(K,slow) by approximately 30 % whilst not affecting the resting conductance. Action potential firing may culminate in opening of K(ATP) channels by activation of ATP-dependent Ca(2+) pumping as suggested by the observation that the sarco-endoplasmic reticulum Ca(2+)-ATPase (SERCA) inhibitor thapsigargin (4 microM) inhibited I(K,slow) by
This question shows a good amount of intuition. It is true that the signal is generally thought to diffuse passively. However, active propagation of dendritic signals is certainly an important property. As opposed to the axon, where the action potential is generated by voltage-gated sodium (Na+) channels, in the dendrites, the voltage gated channels are calcium (Ca2+) channels (VGCC -- voltage gated calcium channels) or non-specific cation (Na+, K+, and Ca2+) channels such as the NMDA channel. The voltage gated nature of these excitatory channels leads to a positive feedback effect similar to that of the action potential itself. However, the time course of these signals is much slower: on the order of 10s to 100s of milliseconds, as opposed to the 1ms time scale of the action potential. These dendritic spikes or calcium spikes or plateau potentials can lead to firing of bursts of action potentials. As a side point, action potentials generated in the soma can actually be propagated backwards ...
This directory contains the Neuron source code for cortical Layer 5 pyramidal cell model and experiments employed in: Distinct Contributions of Na(V)1.6 and Na(V)1.2 in Action Potential Initiation and Backpropagation Wenqin Hu, Cuiping Tian, Tun Li, Mingpo Yang, Han Hou & Yousheng Shu (2009) Nat Neurosci 12(8): 996-1002. Part of model is based on: Mainen, Z. F. and Sejnowski, T. J. Nature 382: 363-6 (1996) Yu, Y., Shu, Y., et al. J Neurosci 28: 7260-72 (2008) Shu, Y., Hasenstaub, A., et al. Nature 441: 761-5. (2006) =============================================== BRIEF OVERVIEW OF THE CONTENTS Three different but related models are involved in this package: 1). A realistic model of Layer 5 pyramidal cell with sophisticatedly described voltage-dependent sodium channels at the axon initial segment. Either action potentials initiation site (figure not shown in the aforementioned paper, see its main text) or backpropagation failure threshold (Supplementary Fig.4 and Fig.8) can be tested here. This ...
A single action potential can travel down the axon. It does not exist at multiple points on the axon at the same time. The active part of the HH model describes the generation of an action potential at a single point. The passive part describes how the action potential travels down the axon. The main problem of passive travel is that the action potential dies down (after one space constant, the action potential will be very small). So nodes of Ranvier have to be spaced much shorter than the space constant in order to regenerate the amplitude of the action potential ...
Squid giant axons internally perfused with a 30 mM NaF solution and bathed in a 100 mM CaCl2 solution, which are known to produce long lasting action potentials in response to pulses of outward current, were investigated. The effects of tetrodotoxin (TTX) and of tetraethylammonium ion (TEA+) on such action potentials were studied. The results are summarized as follows: (a) An addition of 1--3 microM TTX to the external solution altered but did not block the action potentials; it increased the height of the action potential by approximately 15 mV, and it decreased the membrane conductance as the peak of excitation by about two-thirds. (b) Voltage-clamp experiments performed with both NaCl and TTX in the external CaCl2 solution revealed that the TTX-insensitive action potential does not involve a rise in gNa, whereas the experiments performed without TTX showed that the action potential is accompanied by a large rise in gNa. (c) Internally applied TEA+ was shown to selectively block the ...
Sodium entry during an action potential determines the energy efficiency of a neuron. The classic Hodgkin-Huxley model of action potential generation is notoriously inefficient in that regard with about 4 times more charges flowing through the membrane than the theoretical minimum required to achieve the observed depolarization. Yet, recent experimental results show that mammalian neurons are close to the optimal metabolic efficiency and that the dynamics of their voltage-gated channels is significantly different than the one exhibited by the classic Hodgkin-Huxley model during the action potential. Nevertheless, the original Hodgkin-Huxley model is still widely used and rarely to model the squid giant axon from which it was extracted. Here, we introduce a novel family of Hodgkin-Huxley models that correctly account for sodium entry, action potential width and whose voltage-gated channels display a dynamics very similar to the most recent experimental observations in mammalian neurons. We speak ...
Dear Sir / Madam,. I cant patch on cardiomyocytes to record action potentials at 37 degree C using a perforated patch technique. I tried many things, but failed.. Following the suggestions from this forum, I patched the cell at room temperature. After cell got gigaohm sealed, I turned on the temperature controller. At this moment, I found that it was very easy to loss the cell, because of an electric shock?. So late on, I made a little bit changes and did as followings: (1) I turned on the temperature controller but set temperature at 22oC; (2) patched the cell to get gigaohm seal; (3) waited for about 40 minutes to allow Gramicidin to perforate the cell membrane; (4) switched voltage clmap mode to current clamp mode to see if action potential could be induced or not and (5) if the action potential could be seen, then turned the wheel of temperature controller to increase the bath temperature to 37oC at once. But I found that the cell still losed ...
Definition of action current in the Legal Dictionary - by Free online English dictionary and encyclopedia. What is action current? Meaning of action current as a legal term. What does action current mean in law?
Cardiac electrical alternans, characterized by a beat-to-beat alternation in action potential waveform, is a naturally occurring phenomenon, which can occur at sufficiently fast pacing rates. Its presence has been putatively linked to the onset of cardiac reentry, which is a precursor to ventricular fibrillation. Previous studies have shown that closed-loop alternans control techniques that apply a succession of externally administered cycle perturbations at a single site provide limited Show moreCardiac electrical alternans, characterized by a beat-to-beat alternation in action potential waveform, is a naturally occurring phenomenon, which can occur at sufficiently fast pacing rates. Its presence has been putatively linked to the onset of cardiac reentry, which is a precursor to ventricular fibrillation. Previous studies have shown that closed-loop alternans control techniques that apply a succession of externally administered cycle perturbations at a single site provide limited ...
Acute myocardial ischemia is implicated in many cases of fatal arrhythmias.1 2 The basis of ischemic arrhythmogenesis is alteration in the electrical properties of ventricular tissue, leading to changes in action potential conduction.3 4 Altered electrical properties are a result of the pathophysiological conditions of ischemia, which directly affect membrane ionic currents and intracellular and extracellular ionic concentrations.5 6 Therefore, there exist cause-and-effect relationships between ischemia modification of membrane currents and ionic concentrations and ischemia-related changes in action potential conduction. We investigated these cause-and-effect relationships to determine the ionic mechanisms of depressed conduction and development of conduction block during acute ischemia.. Our investigative tool is a theoretical multicellular fiber model that accounts for the major conditions of ischemia at the level of individual ionic currents and concentrations. The fiber is composed of LRd ...
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 ...
In this work, detailed computational models are used to study the electrophysiology of normal epicardium and the arrhythmogenic effects of epicardial cell remodeling post-infarction. The canine epicardial myocyte model described here reproduces a wide range of experimentally observed rate dependent phenomena in cell and tissue. Model behavior depends on updated formulations for the 4-AP sensitive transient outward current: Ito1), the slow component of the delayed rectifier potassium current: IKs), the L-type Ca2+ channel: ICa,L) and the sodium-potassium pump: INaK) fit to data from canine ventricular myocytes. The model shows that Ito1 plays a limited role in potentiating peak ICa,L and Ca2+ release for propagated action potentials: APs), but modulates the time course of action potential duration: APD) restitution. IKs plays an important role in APD shortening at short diastolic intervals but a limited role in AP repolarization at longer cycle lengths. In addition, simulations demonstrate that ICa,L,
1. Simultaneous measurements of action potential and resistance and of action current and impedance change have been made at a single node of Ranvier.. 2. There is a parallelism between action potential, action current, and resistance change measured at a node of Ranvier.. 3. Some implications of these results have been discussed in relation to the corresponding data obtained from the squid giant axon.. ...
Corticotroph releasing hormone (CRH) is one of the major regulatory hormones associated with the neuroendocrine response to stress. Pituitary corticotroph cells generate repetitive action potentials and associated Ca2+ transients in response to the agonist CRH. The mechanisms underlying this process are complex. CRH is known to activate the adenosine 3,5-cyclic monophosphate (cAMP)-dependent protein kinase A (PKA) pathway. PKA phosphorylates L-type voltage-sensitive Ca2+ channels, activating them and contributing to the generation of an action potential and Ca2+ transients. In an earlier Hodgkin-Huxley type mathematical model of this process, LeBeau et al. showed than an increase in the L-type current was sufficient to generate repetitive action potentials from a resting state in the model (LeBeau et al., 1997). However, they found that the action potential frequency of the model was much higher than the observed experimental action potential frequency. This problem was addressed in the ...
Precise spike coordination between the spiking activities of multiple neurons is suggested as an indication of coordinated network activity in active cell assemblies. Spike correlation analysis aims to identify such cooperative network activity by detecting excess spike synchrony in simultaneously recorded multiple neural spike sequences. Cooperative activity is expected to organize dynamically during behavior and cognition; therefore currently available analysis techniques must be extended to enable the estimation of multiple time-varying spike interactions between neurons simultaneously. In particular, new methods must take advantage of the simultaneous observations of multiple neurons by addressing their higher-order dependencies, which cannot be revealed by pairwise analyses alone. In this paper, we develop a method for estimating time-varying spike interactions by means of a state-space analysis. Discretized parallel spike sequences are modeled as multi-variate binary processes using a ...
Previous studies have reported that enhanced antiarrhythmic effects occur when agents that prolong repolarization are combined with agents that block the sodium channels. The mechanism(s) of this interaction have not been elucidated. In this study, the interactions between the prolongation of action potential duration (APD) by a potassium channel blocker and the reduction in the maximal upstroke velocity of phase 0 of action potential (Vmax) by sodium channel blockers were investigated in guinea pig papillary muscle using conventional microelectrode techniques. Agents that produce selective electrophysiologic effects were chosen, including low concentrations of barium chloride (BaCl2), which selectively blocks the inwardly rectifying potassium current without effects on other repolarizing or depolarizing currents, O-demethyl-encainide (ODME), which blocks the activated sodium channel with slow onset/offset kinetics, and mexiletine, which preferentially blocks the inactivated sodium channel with ...
In this simulation action potential initiation, action potential properties and the role of axon initial segment Na+ channels are investigated in a realistic model of a layer 5 pyramidal neuron axon initial segment. The main Na+ channel properties were constrained by experimental data and the axon initial segment was reconstructed. Model parameters were constrained by direct recordings at the axon initial segment ...
The action potential is fundamental to information processing in the brain. Neurons fire action potentials in response to a variety of inputs and action potentials exist in many different shapes, sizes and frequencies. In this course we will begin with a study of ion channels, the membrane bound biochemical switches that give the action potential its shape. Then we will explore the numerous factors that influence the nature of an individual action potential: neuronal morphology, ion channel composition, and intracellular signaling cascades. We will conclude by considering how circuits of diverse neuronal phenotypes integrate synaptic signals, which give rise to sophisticated information processing, learning and memory, and psychiatric disease. Student projects will explore how ion channel abnormalities, so-called channelopathies, influence cognition and behavior.. ...
Summary To understand how the brain works, tools need to be developed that will allow neuroscientists to investigate how interactions between individual neurons lead to emergent networks. Towards this goal, we will develop targetable voltage sensing nanorods that self-insert into the cell membrane and optically and non-invasively record action potentials at the single particle and nanoscale level, at multiple sites and across a large field-of-view. In semiconductors, absorption and emission band edges are modulated by an external electric field, even more so when optically excited electron-hole pairs are confined, giving rise to the quantum confined Stark effect. The physical origin of this effect is in the separation of photoexcited charges, creating a dipole that opposes the external field. The proposed sensors will optically record action potential with unique advantages not offered by other methods: much larger voltage sensitivity, high brightness, and hence single-particle voltage ...
In neurophysiology, several mathematical models of the action potential have been developed, which fall into two basic types. The first type seeks to model the experimental data quantitatively, i.e., to reproduce the measurements of current and voltage exactly. The renowned Hodgkin-Huxley model of the axon from the Loligo squid exemplifies such models. Although qualitatively correct, the H-H model does not describe every type of excitable membrane accurately, since it considers only two ions (sodium and potassium), each with only one type of voltage-sensitive channel. However, other ions such as calcium may be important and there is a great diversity of channels for all ions. As an example, the cardiac action potential illustrates how differently shaped action potentials can be generated on membranes with voltage-sensitive calcium channels and different types of sodium/potassium channels. The second type of mathematical model is a simplification of the first type; the goal is not to reproduce ...
The reliability and temporal precision of signal propagation between neurons is a major constraint for different coding strategies in neuronal networks. In systems that rely on rate coding, input-output functions of neurons are classically described as ratios of mean firing rates, and the precise timing of individual action potentials is not considered a meaningful parameter (Shadlen and Newsome, 1994, 1998). In these systems, synchrony of presynaptic action potentials and reliable synaptic transmission have even been implicated to deteriorate the information content of the postsynaptic spike train (Zador, 1998). For the functioning of a temporal code in neuronal networks, on the other hand, the precision and reliability of synaptic integration is a prerequisite (Abeles, 1991; Konig et al., 1996; Mainen and Sejnowski, 1995; Nowak et al., 1997; Roy and Alloway, 2001), and without exact spike timing in the millisecond range, synchronous activity among neurons that putatively form a functional cell ...
Using the injury potential method, researchers found that certain cells, classified as excitable, suffered sudden and transitory alterations in resting potential, with later return to the initial value (Fig. 1-B). This cycle was named cellular action potential. In 1883, Burdon-Sanderson and Page 2 obtained continuous recordings of the potentials generated by frog cardiac beats. In one of their observations, when an electrode was placed on the intact surface of the heart and another on an injured region, transitory monophasic potential (only one polarity) was recorded in opposition to the known transitory multiphase recordings (positive and negative polarities). This was the origin of the term monophasic action potential (MAP), whose form was very similar to the cellular action potential later obtained by the cellular impalement technique with microelectrodes (IT). In the late 19th century, it was already known that the electric currents generated in each cardiac beat could be detected on the ...
Whole-cell patch-clamp recordings were obtained using Multiclamp 700B patch amplifiers (Molecular Devices), and data were analyzed using pClamp 10 software (Molecular Devices). To characterize basic membrane properties, a series of hyperpolarizing and depolarizing current steps were applied for 500 ms in 10-45 pA increments at 5 s intervals. The action potential threshold was determined for the first spike at the lowest level of depolarizing current required to evoke at least one spike. Action potential spike measurements were taken from the first action potential on the first sweep to reach the threshold. Spike height was measured as the peak membrane voltage relative to threshold, and half-width was measured at the half amplitude of the action potential. Input resistance was determined from the slope of the linear regression taken through the voltage-current relationship in the hyperpolarizing range.. To determine connectivity among C4- and C8-projecting cell populations, simultaneous ...
ABSTRACT: A mathematical model of the cardiac ventricular action potential is presented. In our previous work, the membrane Na+ current and K+ currents were formulated. The present article focuses on processes that regulate intracellular Ca2+ and depend on its concentration. The model presented here for the mammalian ventricular action potential is based mostly on the guinea pig ventricular cell. However, it provides the framework for modeling other types of ventricular cells with appropriate modifications made to account for species differences. The following processes are formulated: Ca2+ current through the L-type channel (ICa), the Na(+)-Ca2+ exchanger, Ca2+ release and uptake by the sarcoplasmic reticulum (SR), buffering of Ca2+ in the SR and in the myoplasm, a Ca2+ pump in the sarcolemma, the Na(+)-K+ pump, and a nonspecific Ca(2+)-activated membrane current. Activation of ICa is an order of magnitude faster than in previous models. Inactivation of ICa depends on both the membrane voltage ...
The cardiac cell action potential, like action potentials in nerves, is divided into five phases, numbered 0 through 4. Two of these, phase 2 (the plateau phase) and phase 4 (the diastolic interval) are marked by little to no change in voltage. Sodium, potassium and calcium are the primary ions.
Mechanisms of action potential (AP) generation in neocortical pyramidal cells have been the focus of intense experimental and theoretical research over the last several decades. It has proven very difficult, however, to arrive at a consensus model which can satisfactorily account for all of its features. One of the still unresolved issues is lack of accurate description of Na+ channel kinetics in different neuronal compartments. Here, we measured kinetics of somatic Na+ channels using high temporal resolution (5-10 kHz, −3dB, low pass four-pole Bessel filter) cell-attached recordings from layer 5 pyramidal neurons in neocortical slices. The data were described by fitting different Markov models with differential evolution fit algorithms. The limited speed of voltage steps and the effect of current filtering were accounted for in the fit procedure. Hodgkin-Huxley-type models which assumed a number of independent activation gates were not the optimal description of the experimentally recorded ...
ABSTRACT: We have developed a detailed mathematical model for Ca handling and ionic currents in the human ventricular myocyte. Our aims were to: (1) simulate basic excitation-contraction coupling phenomena; (2) use realistic repolarizing K current densities; (3) reach steady-state. The model relies on the framework of the rabbit myocyte model previously developed by our group, with subsarcolemmal and junctional compartments where ion channels sense higher [Ca] vs. bulk cytosol. Ion channels and transporters have been modeled on the basis of the most recent experimental data from human ventricular myocytes. Rapidly and slowly inactivating components of I(to) have been formulated to differentiate between endocardial and epicardial myocytes. Transmural gradients of Ca handling proteins and Na pump were also simulated. The model has been validated against a wide set of experimental data including action potential duration (APD) adaptation and restitution, frequency-dependent increase in Ca transient ...
Action potentials in cardiac myocytes have durations in the order of magnitude of 100 milliseconds. In biomedical investigations the documentation of the occurrence of action potentials is often not sufficient, but a recording of the shape of an action potential allows a functional estimation of several molecular players. Therefore a temporal resolution of around 500 images per second is compulsory. In the past such measurements have been performed with photometric approaches limiting the measurement to one cell at a time. In contrast, imaging allows reading out several cells at a time with additional spatial information. Recent developments in camera technologies allow the acquisition with the required speed and sensitivity. We performed action potential imaging on isolated adult cardiomyocytes of guinea pigs utilizing the fluorescent membrane potential sensor di-8-ANEPPS and latest electron-multiplication CCD as well as scientific CMOS cameras of several manufacturers. Furthermore, we ...
TY - JOUR. T1 - Slow integration leads to persistent action potential firing in distal axons of coupled interneurons. AU - Sheffield, Mark E.J.. AU - Best, Tyler K.. AU - Mensh, Brett D.. AU - Kath, William L.. AU - Spruston, Nelson. N1 - Funding Information: We thank T. Klausberger, S. Layton and M. Wilson for providing in vivo spiking data, and M. Benton, M. Nusbaum and members of the Spruston laboratory for helpful discussion and comments on the manuscript. We also thank E. Grodinsky for interneuron reconstructions. Grant support was provided by the US National Institutes of Health (NS-046064 to N.S. and W.L.K.) and the National Alliance for Research on Schizophrenia and Depression (N.S.). M.E.J.S. was supported by a Presidential Fellowship from Northwestern University.. PY - 2011/2. Y1 - 2011/2. N2 - The conventional view of neurons is that synaptic inputs are integrated on a timescale of milliseconds to seconds in the dendrites, with action potential initiation occurring in the axon initial ...
The combination of the rapid and large voltage changes during action potentials and the large sodium current density in Purkinje neurons required careful tuning of the voltage-clamp circuitry for series resistance compensation, as well as reduction of the sodium current to reduce errors arising from imperfect compensation.. A particular concern was whether the overall system, including the partially compensated resistance of the pipette in series with the cell capacitance, allows faithful imposition of voltage using the very narrow spike waveforms of Purkinje neurons, which can have widths at half-amplitude of about 200 μs. In previous experiments (Carter and Bean 2009), we did control experiments using a second electrode to record intracellular voltage while a cell was voltage clamped with a spike waveform. These experiments showed that the action potential command voltage was accurately imposed on the cell membrane, with measured voltage at the peak of the action potential differing from the ...
Elezgarai I, Diez J, Puente N, Azkue JJ, Benitez R, Bilbao A, Knopfel T, Donate-Oliver F & Grandes P (2003). Subcellular localization of the voltage-dependent potassium channel Kv3. 1b in postnatal and adult rat medial nucleus of the trapezoid body. Neuroscience 118, 889-898 ...
Spike correlations between neurons are ubiquitous in cortex, but their role is at present not understood. Here we describe the firing response of a leaky integrate-and-fire neuron when it receives a temporarily correlated input generated by pre-synaptic correlated neuronal populations. Input correlations are characterized in terms of the firing rates, Fano factors, correlation coefficients and correlation time scale of the neurons driving the target neuron. It has been shown [1] that the sum of the pre-synaptic spike trains cannot be well described by a Poisson process. In fact, the total current has a non-trivial two-point correlation function described by two main parameters: the correlation time scale (how precise the input correlations are in time), and the correlation magnitude (how strong they are). Therefore, the total current generated by the input spike trains cannot be approximated by a white noise Gaussian process in the diffusion limit. Instead, the total current is replaced by a ...
This experiment deals with the basic principles behind sodium ion channels in neurons and their effects on action potentials or spikes, how gating properties regulate channel behavior and influence firing.
A method was developed to non-invasively and simultaneously track individual action-potentials propagating across multiple branches of identified neurons in neocortical cultures.
With just-suprathreshold current pulses, FS cells often displayed a considerable delay before the first spike, whereas GIN cells did not (cf. Fig. 2, C and D, top panels). In addition, GIN cells often displayed an afterdepolarization (ADP) following low-frequency action potentials (Fig. 2C, inset; cf. Halabisky et al. 2006). At higher levels of stimulus current, spike frequency adaptation was evident in GIN cells (Fig. 2D, bottom), but not in FS cells (Fig. 2D, bottom). Finally, at higher stimulus currents, the peak of the first action potential in GIN cells was the most positive in the train and the trough of the first afterhyperpolarization (AHP) was the most negative (Fig. 2C, bottom). By contrast, the action potential heights and AHP magnitudes of FS cells changed little under similar conditions (Fig. 2D, bottom). The firing of GIN cells also differed from that of RS cells, whose second action potential peak was substantially more negative than the first and whose first AHP was the most ...
Animal models of dorsal root ganglion (DRG) neurons are widely used in pain research as in vitro models of human nociception, due to a lack of human-specific alternatives. However, these models do not capture human-specific electrophysiology, including differences in ion channel function, and do not address significant inter-neuronal variability, e.g. differences in ion channel expression and action potential morphology between DRG neuron sub-types. This heterogeneity is difficult to address through experiments alone but can result in variable responses to therapies and disease.. We have developed a method for integrating biological variability with in silico modelling, using experimentally-calibrated populations of models, and have used this approach extensively in cardiac electrophysiology. We propose integrating new recordings of human DRG neuron electrophysiology, provided by our collaboration with Anabios Corporation,with our methodology to construct and validate populations of in silico ...
ABSTRACT: BACKGROUND: Computational biology is a powerful tool for elucidating arrhythmogenic mechanisms at the cellular level, where complex interactions between ionic processes determine behavior. A novel theoretical model of the canine ventricular epicardial action potential and calcium cycling was developed and used to investigate ionic mechanisms underlying Ca2+ transient (CaT) and action potential duration (APD) rate dependence. METHODS AND RESULTS: The Ca2+/calmodulin-dependent protein kinase (CaMKII) regulatory pathway was integrated into the model, which included a novel Ca2+-release formulation, Ca2+ subspace, dynamic chloride handling, and formulations for major ion currents based on canine ventricular data. Decreasing pacing cycle length from 8000 to 300 ms shortened APD primarily because of I(Ca(L)) reduction, with additional contributions from I(to1), I(NaK), and late I(Na). CaT amplitude increased as cycle length decreased from 8000 to 500 ms. This positive rate-dependent property ...
Thomas, N, Dupont, E, Halliday, D, Fry, CH and Severs, NJ (2006) An inducible cell system to investigate connexin co-expression and action potential propagation within the heart In: 28th Annual International-Society-for-Heart-Research North American Section Meeting, 2006-06-13 - 2006-06-16, Toronto, CANADA. Full text not available from this repository ...
A long-standing hypothesis is that action potentials initiate first in the axon hillock/initial segment (AH-IS) region because of a locally high density of Na+ channels. We tested this idea in subicular pyramidal neurons by using patch-clamp recordings in hippocampal slices. Simultaneous recordings from the soma and IS confirmed that orthodromic action potentials initiated in the axon and then invaded the soma. However, blocking Na+ channels in the AH-IS with locally applied tetrodotoxin (TTX) did not raise the somatic threshold membrane potential for orthodromic spikes. TTX applied to the axon beyond the AH-IS (30-60 μm from the soma) raised the apparent somatic threshold by ∼8 mV. We estimated the Na+ current density in the AH-IS and somatic membranes by using cell-attached patch-clamp recordings and found similar magnitudes (3-4 pA/μm2). Thus, the present results suggest that orthodromic action potentials initiate in the axon beyond the AH-IS and that the minimum threshold for spike ...
TY - JOUR. T1 - Effects of acetylcholine on action potential characteristics of atrial and ventricular myocardium after bilateral cervical vagotomy in the cat.. AU - Kovacs, R. J.. AU - Bailey, J. C.. PY - 1985/4. Y1 - 1985/4. N2 - Acetylcholine, the parasympathetic neurotransmitter, shortens the action potential duration of cat atrial muscle cells, but not ventricular muscle cells. In mammalian species, atrial tissue receives a richer cholinergic nerve supply than ventricular tissue. To determine whether chronic withdrawal of cholinergic tone might influence the subsequent response of these tissues to cholinergic stimulation, we examined the effect of acetylcholine on the action potentials of atrial and ventricular myocytes from cats with intact vagi and cats after chronic bilateral cervical vagotomy. Following bilateral cervical vagotomy, physostigmine (10(-6) M) failed to alter atrial tension development or action potential duration. Acetylcholine produced shortening of the action potential ...
Variation of apparent amplitude of the action potentials may result from postulated variation in the resistance of receptor membranes, which commonly decreases as the receptor potential deviates from the baseline and increases as it returns. SummaryVoltage fluctuations identified as receptor potentials can be detected with electrodes applied to the mucilage surrounding the head of a tentacle of Drosera intermedia if the head is stimulated by contact with a live insect, by the touch of a clean, inert object, or by application of salt solutions. Associated with a low receptor potential are action potentials, which occur at a frequency dependent on the magnitude of the receptor potential. These action potentials can be detected with electrodes applied to any region of the stalk of the tentacle. Inflection of the lower stalk follows the occurrence of action potentials. Inflection is minute for isolated action potentials but large and rapid when several occur within a brief interval.The apparent amplitude of
Here I demonstrate how to use a single microcontroller pin to generate action-potential-like waveforms. The output is similar my fully analog action potential generator circuit, but the waveform here is created in an entirely different way. A microcontroller is at the core of this project and determines when to fire action potentials. Taking advantage of the pseudo-random number generator (rand() in AVR-GCCs stdlib.h), I am able to easily produce unevenly-spaced action potentials which more accurately reflect those observed in nature. This circuit has a potentiometer to adjust the action potential frequency (probability) and another to adjust the amount of overshoot (afterhyperpolarization, AHP). I created this project because I wanted to practice designing various types of action potential measurement circuits, so creating an action potential generating circuit was an obvious perquisite. The core of this circuit is a capacitor which is charged and discharged by toggling a microcontroller pin ...
The compound muscle action potential (CMAP) or compound motor action potential is an electromyography investigation (electrical study of muscle function). The CMAP idealizes the summation of a group of almost simultaneous action potentials from several muscle fibers in the same area. These are usually evoked by stimulation of the motor nerve. Patients that suffer from critical illness myopathy, which is a frequent cause of weakness seen in patients in hospital intensive care units, have prolonged compound muscle action potential.[1]. ...
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Fig. 1 3DFG SEM imaging and optical characterization.. (A) SEM images of 5-μm 3DFG electrodes. Scale bars, 5 μm (I), 1 μm (II), and 0.5 μm (III). (B) UV-vis absorbance as a function of wavelength for fused silica (gray), 3DFG synthesized at 800°C for 10 min (red), and 3DFG synthesized at 800°C for 30 min (blue). (C) Real (ε1) and imaginary (ε2) parts of the dielectric constant of 3DFG in the visible and near-infrared range. (D) Photocurrent generated at the interface between 3DFG electrodes and PBS under excitation with ultrafast (picosecond) pulsed laser at 1064 nm at varying laser intensities. The pulse trains have a duration of 6 ms. (E) Capacitive and faradaic current components of the photocurrent generated by laser excitation. The capacitive values were taken as the maximum current peak at the onset of the laser excitation. The faradaic values were calculated as the average of the last 1-ms-long portion before the end of the laser pulse train. ...
The action potential (AP) is the basic signaling unit in various crucial physiological processing, for instance, in neurotransmission, muscle contraction, and glandular secretion (Koch, 1990). The classic model animal, Caenorhabditis elegans (or C. elegans), with a simple and compact nervous system, conservatively employs the calcium-mediated all-or-none APs for odor response in AWA olfactory neurons (Liu et al., 2018), as well as for muscle contraction in body wall muscles (Gao and Zhen, 2011; Liu et al., 2011) and pharyngeal muscles (Davis et al., 1999). Plateau potentials were also observed in ASE and RMD neurons (Goodman et al., 1998; Mellem et al., 2008; Lockery et al., 2009; Lockery and Goodman, 2009), though the underlying roles in specific behavior are still elusive. Either in neurons or in muscles, the action potential firing is dependent on the excitatory pre-synaptic vesicles release. The minimum number of the presynaptic vesicles to elicit a single action potential in C. elegans has ...
Ceballos, Cesar C., Antonio C. Roque, and Ricardo M. Leão. A negative slope conductance of the persistent sodium current prolongs subthreshold depolarizations. Biophysical journal 113.10 (2017): 2207-2217.
The secretory epithehum of the mantle of the clam Anomalocardia brasiliana is excitable. The ionic dependence of its action potentials was investigated. Two distinct phases could be recognized by their ionic dependences. The early spike phase, that appeared in all action potentials, was dependent on the Na+ concentration of the solution in the interstitial space and was insensitive to tetrodotoxin (TTX) at concentrations as high as 36μmol l−1. It was inhibited by local anesthetics, and its repolarization was inhibited by veratrine. The data show this electrogenesis is caused by TTX-insensitive sodium channels located at the basolateral membrane of this epithelium. Cardiac-like action potentials were recorded in several specimens: the rapid Na+-dependent spike was followed by a slower repolarization phase that formed a plateau and increased the action potential duration. The plateau amplitude was markedly increased when the external Ca2+ concentration was increased to (60 mmol l−1 and it was ...
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Supervisors: Ole Paulsen, Tanja Fuchsberger. Spike timing-dependent plasticity (STDP) is a physiologically relevant form of Hebbian learning, in which near coincident pre- and postsynaptic firing induces synaptic plasticity: Long term potentiation (LTP) is induced when the presynaptic spike precedes postsynaptic firing, and long term depression (LTD) when postsynaptic firing precedes the presynaptic spike [1]. However, these plasticity rules are profoundly influenced by neuromodulators [2]. Reward, novelty or surprise are correlated with neuromodulatory signals, such as dopamine, acetylcholine or noradrenaline, which modulate memories and behavioural outcome. They regulate STDP through various mechanisms, as they can control the biophysical properties of dendrites, including the dynamics of spike backpropagation, and can influence the state of kinases and phosphatases implicated in synaptic plasticity (Seol et al., 2007). In our laboratory we recently demonstrated a retroactive effect of ...
TY - JOUR. T1 - Layer-specific high-frequency action potential spiking in the prefrontal cortex of awake rats. AU - Boudewijns, Z.S.R.M.. AU - Groen, M.R.. AU - Lodder, B.N.. AU - McMaster, M.T.. AU - Kaleogrades, L.. AU - de Haan, R.. AU - Narayanan, R.T.. AU - Meredith, R.M.. AU - Mansvelder, H.D.. AU - de Kock, C.P.J.. PY - 2013. Y1 - 2013. N2 - Cortical pyramidal neurons show irregular in vivo action potential (AP) spiking with high frequency bursts occurring on sparse background activity. Somatic APs can backpropagate from soma into basal and apical dendrites and locally generate dendritic calcium spikes. The critical AP frequency for generation of such dendritic calcium spikes can be very different depending on cell-type or brain area involved. Previously, it was shown in vitro that calcium electrogenesis can also be induced in L(ayer) 5 pyramidal neurons of prefrontal cortex (PFC). It remains an open question whether somatic burst spiking and the resulting dendritic calcium electrogenesis ...
We correlated primary T wave changes with the changes of monophasic action potentials (MAP) recorded with suction electrodes from the ventricular surface of the dog heart following systemic or intracoronary infusions of small doses of isoproterenol (ISP). The portions of the heart perfused with ISP were excised and weighed to determine the mass of perfused tissue. ISP shortened the ventricular MAP by an average of 12-18 msec in the entire ventricular mass following systemic administration, in 34 plus or minus 6 per cent of the ventricular mass after injection into the left circumflex coronary artery (LCA), in 8.5 plus or minus 2.6% of the ventricular mass after injection into a branch of LCA and in 17 plus or minus 8 per cent of the ventricular mass after injection into the right CA. The MAP changes induced by ISP were similar to the transmembrane action potential changes recorded with microelectrodes from papillary muscles excised from the same dogs. The most important results of this study ...
Rhythmic patterns of neuronal activity have been found at multiple levels of various sensory systems. In the olfactory bulb or the antennal lobe, oscillatory activity exhibits a broad range of frequencies and has been proposed to encode sensory information. However, the neural mechanisms underlying …
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TY - JOUR. T1 - Learning-induced afterhyperpolarization reductions in hippocampus are specific for cell type and potassium conductance. AU - de Jonge, M. C.. AU - Black, J.. AU - Deyo, R. A.. AU - Disterhoft, J. F.. PY - 1990/5. Y1 - 1990/5. N2 - Hippocampal slices were prepared from rabbits trained in a trace eye-blink conditioning task and from naive and pseudoconditioned controls. Measurements of the post-burst afterhyperpolarization (AHP), action potential, and other cellular properties were obtained from intracellular recordings of CA1 pyramidal (N=49) and dentate gyrus granule cells (N=52). A conditioning-specific reduction in the amplitude of the AHP was found in CA1 cells but not in dentate granule cells. This reduction in the AHP was apparent at 50 ms after the end of a depolarizing current pulse, and was maintained for at least 650 ms. Other measured cell characteristics (input resistance, resting membrane potential, action potential shape, inward rectification, spike threshold) were ...
Kv3 voltage-gated potassium channels (Kv3.1-4) are activated by depolarization of the neuronal plasma membrane to potentials above -20 mV; they open rapidly during the depolarising phase of the neuronal action potential to initiate repolarisation and prevent sodium channel inactivation. As the neuron begins to repolarise, the channels deactivate quickly and so do not contribute significantly to the after-hyperpolarisation [xii] [xiii]. These distinct properties allow the channels to terminate the action potential rapidly without compromising action potential threshold, rise time, or magnitude, and without increasing the duration of the refractory period that follows. Consequently, neurons expressing Kv3 channels can sustain action potential firing at high frequencies [xiv]. Kv3.1-3 subtypes are expressed mainly in the central nervous system, whereas Kv3.4 channels are predominant in skeletal muscle and sympathetic neurons [xv]. Kv3.1-3 channel subtypes are differentially expressed in ...
From some sources, Ive read that excitatory postsynaptic potentials (EPSPs) decay over time, which would imply that they arent abolished by action potentials. However, other sources seem to indicate the opposite (although I may be misunderstanding them). Plus, the classical leaky-integrate-and-fire neuron model implies that EPSPs are abolished by action potentials (although this could well be a simplification). Does the refractory period of an action potential affect its originating EPSP? Or is it a separate phenomenon?. ...
Derivation of a new force field for crystal-structure prediction using global optimization: nonbonded potential parameters for hydrocarbons and alcohols
Sinoatrial nodal cells (SANCs) generate spontaneous action potentials (APs) that control the cardiac rate. The brain modulates SANC automaticity, via the autonomic nervous system, by stimulating membrane receptors that activate (adrenergic) or inactivate (cholinergic) adenylyl cyclase (AC). However, these opposing afferents are not simply additive. We showed that activation of adrenergic signaling increases AC-cAMP/PKA signaling, which mediates the increase in the SANC AP firing rate (i.e., positive chronotropic modulation). However, there is a limited understanding of the underlying internal pacemaker mechanisms involved in the crosstalk between cholinergic receptors and the decrease in the SANC AP firing rate (i.e., negative chronotropic modulation). We hypothesize that changes in AC-cAMP/PKA activity are crucial for mediating either decrease or increase in the AP firing rate and that the change in rate is due to both internal and membrane mechanisms. In cultured adult rabbit pacemaker cells infected
Intracellular recordings were obtained from rat neocortical neurons in vitro. The current-voltage-relationship of the neuronal membrane was investigated using current- and single-electrode-voltage-clamp techniques. Within the potential range up to 25 mV positive to the resting membrane potential (RMP: -75 to -80 mV) the steady state slope resistance increased with depolarization (i.e. steady state inward rectification in depolarizing direction). Replacement of extracellular NaCl with an equimolar amount of choline chloride resulted in the conversion of the steady state inward rectification to an outward rectification, suggesting the presence of a voltage-dependent, persistent sodium current which generated the steady state inward rectification of these neurons. Intracellularly injected outward current pulses with just subthreshold intensities elicited a transient depolarizing potential which invariably triggered the first action potential upon an increase in current strength. ...
can be generated along the axon while the threshold potential is reached. The greater the strength of the stimulus, causing the membrane depolarisation process to occur. Subsequently, some [[Sodium_voltage-gated_ion_channels,voltage-gated Na,sup,+,/sup, channels]] are opened, allowing the [[Sodium,Na,sup,+,/sup,]] ions to move across the membrane into the intracellular environment. The neuronal membrane now becomes slightly positive, relative to the outside of membrane. As the membrane potential shift from -70 mV to more positive value, the threshold potential is reached, causing all of the voltage-gated Na+ channel to open, creating a rapid rise of membrane potential value into the maximum, +60 mV. During depolarisation, the membrane potential value would not exceed the amount of +60mV as it is the equilibrium potential of Na,sup,+,/sup, ,ref,http://people.eku.edu/ritchisong/301notes2.htm,/ref ...
Studies on isolated inside-out patches have revealed that the pancreatic α-cells paradoxically contain a high density of KATP channels (14). In the pancreatic β-cells, glucose inhibits the KATP channels and thus leads to stimulation of electrical activity and insulin secretion (33,34). Yet, if closure of KATP channels in β-cells results in stimulation of insulin secretion, how can closure of the same channels in α-cells inhibit glucagon secretion? We have proposed that the answer to this conundrum lies in the distinct electrophysiological properties of the α- and β-cells (Fig. 6; see also Fig. 2). Thus, whereas β-cell electrical activity and secretion are principally dependent on L-type Ca2+ channels, α-cell action potential firing involves voltage-gated Na+ channels. Unlike the L-type Ca2+ channels, the Na+ channels undergo voltage-dependent inactivation (i.e., they enter a nonconducting state when the voltage becomes too positive) (7). Closure of the KATP channels with resultant ...
We have evaluated an intracardiac technique for the study of the electrophysiological patterns of early or subendocardial ischaemia in man. Simultaneous recordings of the paced endocardial evoked response and monophasic action potentials were obtained during pacing stress testing in 10 patients with reversible myocardial ischaemia. Early patterns of change occurred in both these recordings in response to regional ischaemia. Abnormal rate corrected shortening of the local repolarisation time in the paced endocardial evoked response from the left ventricular ischaemic zone diverging from control non-ischaemic values by a mean of 10.6% was paralleled by decreases in the simultaneous paced monophasic action potentials duration. A differential delay in the local activation time and conduction was also documented by the paced endocardial evoked response and monophasic action potential electrodes. Non-ischaemic control zones showed no changes in the pattern of activation and repolarisation. Disparate ...
Spontaneous activation and contraction of the heart are a consequence of the specialized pacemaking tissue in these anatomic locales. As described in Chap. 238, action potentials in the heart are regionally heterogeneous. The action potentials in cells isolated from nodal tissue are distinct from those recorded from atrial and ventricular myocytes (Fig. 239-1). The complement of ionic currents present in nodal cells results in a less negative resting membrane potential compared with atrial or ventricular myocytes. Electrical diastole in nodal cells is characterized by slow diastolic depolarization (phase 4), which generates an action potential as the membrane voltage reaches threshold. The action potential upstrokes (phase 0) are slow compared with atrial or ventricular myocytes, being mediated by calcium rather than sodium current. Cells with properties of SA and AV nodal tissue are electrically connected to the remainder of the myocardium by cells with an electrophysiologic phenotype between ...
The basal forebrain (BF) has long been implicated in attention, learning and memory, and recent studies have established a causal relationship between artificial BF activation and arousal. However, neural ensemble dynamics in the BF still remains unclear. Here, recording neural population activity in the BF and comparing it with simultaneously recorded cortical population under both anesthetized and unanesthetized conditions, we investigate the difference in the structure of spontaneous population activity between the BF and the auditory cortex (AC) in mice. The AC neuronal population show a skewed spike rate distribution, a higher proportion of short (≤80 ms) inter-spike intervals (ISIs) and a rich repertoire of rhythmic firing across frequencies. Although the distribution of spontaneous firing rate in the BF is also skewed, a proportion of short ISIs can be explained by a Poisson model at short time scales (≤20 ms) and spike count correlations are lower compared to AC cells, with optogenetically
p,Transduction of graded synaptic input into trains of all-or-none action potentials (spikes) is a crucial step in neural coding. Hodgkin identified three classes of neurons with qualitatively different analog-to-digital transduction properties. Despite widespread use of this classification scheme, a generalizable explanation of its biophysical basis has not been described. We recorded from spinal sensory neurons representing each class and reproduced their transduction properties in a minimal model. With phase plane and bifurcation analysis, each class of excitability was shown to derive from distinct spike initiating dynamics. Excitability could be converted between all three classes by varying single parameters; moreover, several parameters, when varied one at a time, had functionally equivalent effects on excitability. From this, we conclude that the spike-initiating dynamics associated with each of Hodgkins classes represent different outcomes in a nonlinear competition between oppositely ...
TY - JOUR. T1 - Simulation of Ca-calmodulin-dependent protein kinase II on rabbit ventricular myocyte ion currents and action potentials. AU - Grandi, Eleonora. AU - Puglisi, Jose L.. AU - Wagner, Stefan. AU - Maier, Lars S.. AU - Severi, Stefano. AU - Bers, Donald M. PY - 2007/12/1. Y1 - 2007/12/1. N2 - Ca-calmodulin-dependent protein kinase II (CaMKII) was recently shown to alter Na+ channel gating and recapitulate a human Na+ channel genetic mutation that causes an unusual combined arrhythmogenic phenotype in patients: simultaneous long QT syndrome and Brugada syndrome. CaMKII is upregulated in heart failure where arrhythmias are common, and CaMKII inhibition can reduce arrhythmias. Thus, CaMKII-dependent channel modulation may contribute to acquired arrhythmic disease. We developed a Markovian Na + channel model including CaMKII-dependent changes, and incorporated it into a comprehensive myocyte action potential (AP) model with Na+ and Ca2+ transport. CaMKII shifts Na+ current (I Na) ...
In this video, I want to talk about how action potentials are generated the trigger zone and how theyre conducted down the axon. So Ive drawn a soma here in red and one axon in green. And Ive blown up the axon to a very large size just so I had some room to draw. Heres our graph of the membrane potential on the y-axis and time on the x-axis. And now Ive put a couple of different kinds of ion channels in the membrane of the axon. The first in this lighter grey are the leak channels that we talked about when we talked about the neuron resting potential. These channels are open all the time. Theyre not gated. And I have not drawn any ligand gated ion channels like the neurotransmitter receptors that occur on the soma and the dendrites. But to talk about the action potential, I need to introduce an entirely new type of channel that Ive drawn in dark grey with this little v. And these are voltage gated ion channels. The membrane of an axon as many voltage gated ion channels, most of which open ...