Occurrence Of Action Potentials Research Articles

Modulation of post-pacing action potential duration and contractile responses on ventricular arrhythmogenesis in chloroquine-induced long QT syndrome

BackgroundExcitation-contraction (E-C) coupling, the interaction of action potential duration (APD) and contractility, plays an essential role in arrhythmogenesis. We aimed to investigate the arrhythmogenic role of E-C coupling in the right ventricular outflow tract (RVOT) in the chloroquine-induced long QT syndrome. MethodsConventional microelectrodes were used to record electrical and mechanical activity simultaneously under electrical pacing (cycle lengths from 1000–100 ms) in rabbit RVOT tissue preparations before and after chloroquine with and without azithromycin. KB-R7943 (a Na+-Ca2+ exchanger [NCX] inhibitor), ranolazine (a late sodium current inhibitor), or MgSO4 were used to assess their pharmacological responses in the chloroquine-induced long QT syndrome. ResultsSequential infusion of chloroquine and chloroquine plus azithromycin triggered ventricular tachycardia (VT) (33.7%) after rapid pacing compared to baseline (6.7%, p = 0.004). There were greater post-pacing increases of the first occurrence of contractility (ΔContractility) in the VT group (VT vs. non-VT: 521.2 ± 50.5% vs. 306.5 ± 26.8%, p < 0.001). There was no difference in the first occurrence of action potential at 90% repolarization (ΔAPD90) (VT vs. non-VT: 49.7 ± 7.4 ms vs. 51.8 ± 13.1 ms, p = 0.914). Pacing-induced VT could be suppressed to baseline levels by KB-R7943 or MgSO4. Ranolazine did not suppress pacing-induced VT in chloroquine-treated RVOT. ΔContractility was reduced by KB-R7943 and MgSO4, but not by ranolazine. ConclusionΔContractility (but not ΔAPD) played a crucial role in the genesis of pacing-induced VT in the long QT tissue model, which can be modulated by NCX (but not late sodium current) inhibition or MgSO4.

Tracing the Epileptic Consequences of Neurocysticercosis

Abstract: This Paper aims to provide a detailed overview of some basic and complex topics in the field of Neuroscience. Focusing on the overall occurrence of Action Potentials in Nerve cells, an insightful description of the processes which take place at the cellular and molecular levels is also provided. What follows is a discussion on how Neurocysticercosis, a parasitic infection which adversely affects the Central Nervous System, leads to Epileptic Consequences in the human body, as stated in the title. The explanation of these consequences contains vital information as to how such complex diseases and their consequences are merely errors in Action Potentials at the cellular level. With this, the paper also uses information from previously conducted studies, which found a causal linkage between Neurocysticercosis and Epilepsy. Keywords: Action Potentials; Neurocysticercosis; Epilepsy; Neuroscience; Central Nervous System; Pork Tapeworm; Taenia Solium

A Method for Recording the Bioelectrical Activity of Neural Axons upon Stimulation with Short Pulses of Infrared Laser Radiation.

The aim of the study was to develop a method for long-term non-invasive recording of the bioelectrical activity induced in isolated neuronal axons irradiated with short infrared (IR) pulses and to study the effect of radiation on the occurrence of action potentials in axons of a neuron culture in vitro.Materials and Methods.Hippocampal cells of mouse embryos (E18) were cultured in microfluidic chips made of polydimethylsiloxane and containing microchannels for axonal growth at a distance of up to 800 μm. We studied the electrophysiological activity of a neuronal culture induced by pulses of focused laser radiation in the IR range (1907 and 2095 nm). The electrophysiological activity of the neuronal culture was recorded using a multichannel recording system (Multi Channel Systems, Germany).Results.The developed microfluidic chip and the optical stimulation system combined with the multichannel registration system made it possible to non-invasively record the action potentials caused by pulsed IR radiation in isolated neuronal axons in vitro. The propagation of action potentials in axons was detected using extracellular microelectrodes when the cells were irradiated with a laser at a wavelength of 1907 nm with a radiation power of 0.2–0.5 W for pulses with a duration of 6 ms and 0.5 W for pulses with a duration of 10 ms. It was shown that the radiation power positively correlated with the occurrence rate of axonal response. Moreover, the probability of a response evoked by optical stimulation increased at short optical pulses. In addition, we found that more responses could be evoked by irradiating the neuronal cell culture itself rather than the axon-containing microchannels.Conclusion.The developed method makes it possible to isolate the axons growing from cultured neurons into a microfluidic chip, stimulate the neurons with infrared radiation, and non-invasively record the axonal spiking. The proposed approach allowed us to study the characteristics of neuronal responses in cell cultures over a long (weeks) period of time. The method can be used both in fundamental research into the brain signaling system and in the development of a non-invasive neuro-interface.

Concurrent increases in post-pacing action potential duration and contractility predict occurrence of ventricular arrhythmia.

Excitation-contraction coupling from the integration of action potential duration (APD) and muscle contractility plays an important role in arrhythmogenesis. We aimed to determine whether distinctive excitation-contraction coupling contributes to the genesis of ventricular tachycardias (VTs). Action potential (AP) and mechanical activity were simultaneously recorded under electrical pacing (cycle lengths from 1000 to 100 ms) in the tissue model created from isolated rabbit right ventricular outflow tracts treated with NS 5806 (10 μM, transient outward potassium current enhancer), pinacidil (2 μM, ATP-sensitive potassium channel opener), and pilsicainide (5 μM, sodium channel blocker). There were 15 (9.9%) inducible VT episodes (group 1) and 136 (90.1%) non-inducible VT episodes (group 2) in our tissue model. Group 1 had greater post-pacing increases of the first occurrence of AP at 90% repolarization (ΔAPD90, p < 0.001) and contractility (ΔContractility, p = 0.003) compared with group 2. Triggered VT episodes were common (72.7%) in cases with a ΔAPD90 > 15% and a ΔContractility > 270%, but were undetectable in those with a ΔAPD90 < 15% and a ΔContractility < 270%. In those with pacing-induced VTs, KB-R7943 (10 μM, a Na+-Ca2+ exchanger inhibitor, NCX inhibitor) significantly reduced the occurrence of VTs from 100.0 to 20.0% (15/15 to 3/15 episodes, p < 0.001). Concurrent increases in both post-pacing APD and contractility resulted in the occurrence of ventricular arrhythmias. NCX inhibition may be a potential therapeutic strategy for ventricular arrhythmias.

Energy estimation and coupling synchronization between biophysical neurons

Static charges can induce spatial electric field while moving charges can induce magnetic field. As a result, continuous pumping and exchange of intercellular and extracellular Calcium, potassium and sodium of cells will generate time-varying magnetic field in the media. Therefore, the physical effect of electromagnetic induction in neural activities should be included in building biological neurons. On the other hand, the occurrence of action potential and propagation of ions require energy consumption and supply, so the estimation of physical energy becomes important. Based on our memristive biophysical neuron model, the Hamilton energy function is obtained by using the Helmholtz’s theorem, and this energy is contributed by the electric field and magnetic field described by magnetic flux. It is found that this improved neuron model can present the main dynamical properties in neural activities, and it characterizes the lower threshold behavior and subthreshold oscillation during refractory period. The external forcing current on an isolate is adjusted to calculate the firing patterns, energy function and mode transition, which shows the dependence of energy on electrical activities. Finally, magnetic coupling is triggered to modulate the phase synchronization between two identical neurons connected by electric synapse, respectively.

PAR1 contribution in acute electrophysiological properties of oral anticoagulants in rabbit pulmonary vein sleeve preparations.

Whether oral anticoagulants, vitamin K antagonists (VKAs), and nonvitamin K oral anticoagulant (NOACs) frequently prescribed to atrial fibrillation (AF) patients, do themselves have a pro- or anti-arrhythmic effect have never been addressed. Transmembrane action potentials were recorded in an acute rabbit model of superfused pulmonary veins (PVs) sleeves preparations using standard microelectrode technique. Fluindione 10μm (n=6) increased the AP (action potential) duration (APD), induced a significantly Vmax depression (from 95±14 to 53±5V/s, P<0.05), and 2:1 blocks during rapid atrial pacing thus evoking class I anti-arrhythmic properties, and prevented spontaneous trigger APs. Apixaban 10μm (n=6) increased the APD, significantly prolonged the effective refractory period (from 56.3±4.2 to 72.0±8.6ms, P<0.05), and prevented triggered APs occurrence. Fluindione and apixaban effects were suppressed with the addition of the protease-activated receptors 1 (PAR 1) agonist SFLLR-NH2 . Warfarin 10μm (n=6) significantly abbreviated the early refractory period (from 56.3±4.2 to 45.0±2.2ms, P<0.05) and increased triggered APs occurrence that were successfully prevented by nifedipine but not by the addition of the protease-activated receptors 1 agonist SFLLR-NH2 . In this acute rabbit PVs model, VKAs and NOACs, at physiological concentrations, exhibited very different pharmacological properties that influence PVs electrophysiology, implying PAR1, with fluindione and apixaban which exhibited more anti-arrhythmic properties, whereas warfarin exhibited more pro-arrhythmic properties.

Mapping Micro-Circuits with Extra-Cellular Arrays in Three Layered Cortex

Mapping Micro-Circuits with Extra-Cellular Arrays in Three Layered Cortex

Optimizing Spike-Sorting Yield through Selection of Optimal Recording Sites in High-density Microelectrode Arrays

Optimizing Spike-Sorting Yield through Selection of Optimal Recording Sites in High-density Microelectrode Arrays

Simultaneous Sodium and Calcium Imaging from Dendrites and Axons.

Dynamic calcium imaging is a major technique of neuroscientists. It can reveal information about the location of various calcium channels and calcium permeable receptors, the time course, magnitude, and location of intracellular calcium concentration ([Ca2+]i) changes, and indirectly, the occurrence of action potentials. Dynamic sodium imaging, a less exploited technique, can reveal analogous information related to sodium signaling. In some cases, like the examination of AMPA and NMDA receptor signaling, measurements of both [Ca2+]i and [Na+]i changes in the same preparation may provide more information than separate measurements. To this end, we developed a technique to simultaneously measure both signals at high speed and sufficient sensitivity to detect localized physiologic events. This approach has advantages over sequential imaging because the preparation may not respond identically in different trials. We designed custom dichroic and emission filters to allow the separate detection of the fluorescence of sodium and calcium indicators loaded together into a single neuron in a brain slice from the hippocampus of Sprague-Dawley rats. We then used high-intensity light emitting diodes (LEDs) to alternately excite the two indicators at the appropriate wavelengths. These pulses were synchronized with the frames of a CCD camera running at 500 Hz. Software then separated the data streams to provide independent sodium and calcium signals. With this system we could detect [Ca2+]i and [Na+]i changes from single action potentials in axons and synaptically evoked signals in dendrites, both with submicron resolution and a good signal-to-noise ratio (S/N).

Quantitation of Chronic and Acute Treatment Effects on Neuronal Network Activity Using Image and Signal Analysis: Toward a High-Content Assay

Upon maturation, primary neuronal cultures form an interconnected network based on neurite outgrowth and synaptogenesis in which spontaneous electrical activity arises. Measurement of network activity allows quantification of neuronal health and maturation. A fluorescent indicator was used to monitor secondary calcium influxes after the occurrence of action potentials, allowing us to examine activity of hippocampal cultures via confocal live cell imaging. Subsequently, nuclear staining with DAPI allows accurate cell segmentation. To analyze the calcium recording in a robust, observer-independent manner, we implemented an automated image- and signal-processing algorithm and validated it against a visual, interactive procedure. Both methods yielded similar results on the emergence of synchronized activity and allowed robust quantitative measurement of acute and chronic modulation of drugs on network activity. Both the number of days in vitro (DIV) and neutralization of nerve growth factor (NGF) have a significant effect on synchronous burst frequency and correlation. Acute effects are demonstrated using 5-HT (serotonin) and ethylene glycol tetra-acetic acid. Automated analysis allowed measuring additional features, such as peak decay times and bursting frequency of individual neurons. Based on neuronal cell cultures in 96-well plates and accurate calcium recordings, the analysis method allows development of an integrated high-content screening assay. Because molecular biological techniques can be applied to assess the influence of genes on network activity, it is applicable for neurotoxicity or neurotrophics screening as well as development of in vitro disease models via, for example, pharmacologic manipulation or RNAi.

Roles of I(f) and intracellular Ca2+ release in spontaneous activity of ventricular cardiomyocytes during murine embryonic development

In recent years, the contribution of I(f), an important pacemaker current, and intracellular Ca(2+) release (ICR) from sarcoplasmic reticulum to pacemaking and arrhythmia has been intensively studied. However, their functional roles in embryonic heart remain uncertain. Using patch clamp, Ca(2+) imaging, and RT-PCR, we found that I(f) regulated the firing rate in early and late stage embryonic ventricular cells, as ivabradine (30 µM), a specific blocker of I(f), slowed down action potential (AP) frequency. This inhibitory effect was even stronger in late stage cells, though I(f) was down-regulated. In contrast to I(f), ICR was found to be indispensable for the occurrence of APs in ventricular cells of different stages, because abolishment of ICR with ryanodine and 2-aminoethoxydiphenyl borate (2-APB), specific blockers of ryanodine receptors (RyRs) and inositol trisphosphate receptors (IP3Rs), completely abolished APs. In addition, we noticed that RyR- and IP3R-mediated ICR coexisted in early-stage ventricular cells and RyRs functionally dominated. While at late stage RyRs, but not IP3Rs, mediated ICR. In both early and late stage ventricular cells, Na-Ca exchanger current (I(Na/Ca)) mediated ICR-triggered depolarization of membrane potential and resulted in the initiation of APs. We also observed that different from I(f), which presented as the substantial component of the earlier diastolic depolarization current, application of ryanodine, and/or 2-APB slowed the late phase of diastolic depolarization. Thus, we conclude that in murine embryonic ventricular cells I(f) regulates firing rate, while RyRs and IP3Rs (early stage) or RyRs (late stage)-mediated ICR determines the occurrence of APs.

MMPs and Soluble ICAM-5 Increase Neuronal Excitability within In Vitro Networks of Hippocampal Neurons

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that are released from neurons in an activity dependent manner. Published studies suggest their activity is important to varied forms of learning and memory. At least one MMP can stimulate an increase in the size of dendritic spines, structures which represent the post synaptic component for a large number of glutamatergic synapses. This change may be associated with increased synaptic glutamate receptor incorporation, and an increased amplitude and/or frequency of α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) mini excitatory post-synaptic currents (EPSCs). An associated increase in the probability of action potential occurrence would be expected. While the mechanism(s) by which MMPs may influence synaptic structure and function are not completely understood, MMP dependent shedding of specific cell adhesion molecules (CAMs) could play an important role. CAMs are ideally positioned to be cleaved by synaptically released MMPs, and shed N terminal domains could potentially interact with previously unengaged integrins to stimulate dendritic actin polymerization with spine expansion. In the present study, we have used multielectrode arrays (MEAs) to investigate MMP and soluble CAM dependent changes in neuronal activity recorded from hippocampal cultures. We have focused on intercellular adhesion molecule-5 (ICAM-5) in particular, as this CAM is expressed on glutamatergic dendrites and shed in an MMP dependent manner. We show that chemical long-term potentiation (cLTP) evoked changes in recorded activity, and the dynamics of action potential bursts in particular, are altered by MMP inhibition. A blocking antibody to β1 integrins has a similar effect. We also show that the ectodomain of ICAM-5 can stimulate β1 integrin dependent increases in spike counts and burst number. These results support a growing body of literature suggesting that MMPs have important effects on neuronal excitability. They also support the possibility that MMP dependent shedding of specific synaptic CAMs can contribute to these effects.

A comparative analysis of integrating visual information in local neuronal ensembles

Spike directivity, a new measure that quantifies the transient charge density dynamics within action potentials provides better results in discriminating different categories of visual object recognition. Specifically, intracranial recordings from medial temporal lobe (MTL) of epileptic patients have been analyzed using firing rate, interspike intervals and spike directivity. A comparative statistical analysis of the same spikes from a local ensemble of four selected neurons shows that electrical patterns in these neurons display higher separability to input images compared to spike timing features. If the observation vector includes data from all four neurons then the comparative analysis shows a highly significant separation between categories for spike directivity (p=0.0023) and does not display separability for interspike interval (p=0.3768) and firing rate (p=0.5492). Since electrical patterns in neuronal spikes provide information regarding different presented objects this result shows that related information is intracellularly processed in neurons and carried out within a millisecond-level time domain of action potential occurrence. This significant statistical outcome obtained from a local ensemble of four neurons suggests that meaningful information can be electrically inferred at the network level to generate a better discrimination of presented images.

Studies of first phase insulin secretion using imposed plasma membrane depolarization

The first phase of glucose-induced insulin secretion is generally regarded to represent the release of a finite pool of secretion-ready granules, triggered by the depolarization-induced influx of Ca2+ through L-type Ca2+ channels. However, the experimental induction of insulin secretion by imposed plasma membrane depolarization may be more complicated than currently appreciated. A comparison of the effects of high K+ concentrations with those of KATP channel closure, which initiates the electrical activity of the beta cell, suggests that 40 mM K+, which is a popular tool to produce a first phase-like secretion, is of supraphysiological strength, whereas the 20 mV depolarization by 15 mM K+ is nearly inefficient. A major conceptual problem consists in the occurrence of action potentials during KATP channel closure, but not during K+ depolarization, which leaves the K+ channel conductance unchanged. Recent observations suggest that the signal function of the endogenously generated depolarization is not homogeneous, but may rather differ between the component mainly determined by KATP channel closure (slow waves) and that mainly determined by Ca2+ influx (action potentials).

The motor neuron recruitment strategy and muscle anatomical properties determine the influence of synaptic noise on the variability of motor output

The motor neuron recruitment strategy and muscle anatomical properties determine the influence of synaptic noise on the variability of motor output

Origin of correlated activity between parasol retinal ganglion cells

Cells throughout the central nervous system exhibit synchronous activity patterns - i.e. a cell’s probability of generating an action potential depends both on its firing rate and on the occurrence of action potentials in surrounding cells. The mechanisms producing synchronous or correlated activity are poorly understood despite its prevalence and potential impact on neural coding. We find that neighboring parasol retinal ganglion cells receive strongly correlated synaptic input in the absence of modulated light stimuli. This correlated variability appeared to arise through the same circuits that provide uncorrelated synaptic input. In addition, ON but not OFF parasol cells were coupled electrically. Correlated variability in synaptic input, however, dominated correlations in the parasol spike outputs and shared variability in the timing of action potentials generated by neighboring cells. These results provide a mechanistic picture of how correlated activity is produced in a population of neurons of key importance to visual perception.

Effect of Stimulus Intensity on the Spike–Local Field Potential Relationship in the Secondary Somatosensory Cortex

Neuronal oscillations in the gamma frequency range have been reported in many cortical areas, but the role they play in cortical processing remains unclear. We tested a recently proposed hypothesis that the intensity of sensory input is coded in the timing of action potentials relative to the phase of gamma oscillations, thus converting amplitude information to a temporal code. We recorded spikes and local field potential (LFP) from secondary somatosensory (SII) cortex in awake monkeys while presenting a vibratory stimulus at different amplitudes. We developed a novel technique based on matching pursuit to study the interaction between the highly transient gamma oscillations and spikes with high time-frequency resolution. We found that spikes were weakly coupled to LFP oscillations in the gamma frequency range (40-80 Hz), and strongly coupled to oscillations in higher gamma frequencies. However, the phase relationship of neither low-gamma nor high-gamma oscillations changed with stimulus intensity, even with a 10-fold increase. We conclude that, in SII, gamma oscillations are synchronized with spikes, but their phase does not vary with stimulus intensity. Furthermore, high-gamma oscillations (>60 Hz) appear to be closely linked to the occurrence of action potentials, suggesting that LFP high-gamma power could be a sensitive index of the population firing rate near the microelectrode.

An improved method for the estimation of firing rate dynamics using an optimal digital filter

In most neural systems, neurons communicate by means of sequences of action potentials or ‘spikes’. Information encoded by spike trains is often quantified in terms of the firing rate which emphasizes the frequency of occurrence of action potentials rather than their exact timing. Common methods for estimating firing rates include the rate histogram, the reciprocal interspike interval, and the spike density function. In this study, we demonstrate the limitations of these aforementioned techniques and propose a simple yet more robust alternative. By convolving the spike train with an optimally designed Kaiser window, we show that more robust estimates of firing rate are obtained for both low and high-frequency inputs. We illustrate our approach by considering spike trains generated by simulated as well as experimental data obtained from single-unit recordings of first-order sensory neurons in the vestibular system. Improvements were seen in the prevention of aliasing, phase and amplitude distortion, as well as in the noise reduction for sinusoidal and more complex input profiles. We review the generality of the approach, and show that it can be adapted to describe neurons with sensory or motor responses that are characterized by marked nonlinearities. We conclude that our method permits more robust estimates of neural dynamics than conventional techniques across all stimulus conditions.

Cell type‐specific relationships between spiking and [Ca2+]i in neurons of the Xenopus tadpole olfactory bulb

Multi-neuronal recordings with Ca2+ indicator dyes usually relate [Ca2+]i to action potentials (APs) assuming a stereotypical dependency between the two. However, [Ca2+]i affects and is affected by numerous complex mechanisms that differ from cell type to cell type, from cell compartment to cell compartment. Moreover, [Ca2+]i depends on the specific way a cell is activated. Here we investigate, by combining calcium imaging and on-cell patch clamp recordings, the relationship between APs (spiking) and somatic [Ca2+]i in mitral and granule cells of the olfactory bulb in Xenopus laevis tadpoles. Both cell types exhibit ongoing and odour-modulated [Ca2+]i dynamics. In mitral cells, the occurrence of APs in both spontaneous and odour-evoked situations correlates tightly to step-like [Ca2+]i increases. Moreover, odorant-induced suppression of spontaneous firing couples to a decrease in [Ca2+]i. In contrast, granule cells show a substantial number of uncorrelated events such as increases in [Ca2+]i without APs occurring or APs without any effect upon [Ca2+]i. The correlation between spiking and [Ca2+]i is low, possibly due to somatic NMDAR-mediated and subthreshold voltage-activated Ca2+ entries, and thus does not allow a reliable prediction of APs based on calcium imaging. Taken together, our results demonstrate that the relationship between somatic [Ca2+]i and APs can be cell type specific. Taking [Ca2+]i dynamics as an indicator for spiking activity is thus only reliable if the correlation has been established in the system of interest. When [Ca2+]i and APs are precisely correlated, fast calcium imaging is an extremely valuable tool for determining spatiotemporal patterns of APs in neuronal population.

Behaviorally relevant endocannabinoid action in hippocampus: dependence on temporal summation of multiple inputs

Endocannabinoids have been shown to mediate depolarization-induced suppression of GABAergic inhibition (DSI), possibly via release and retrograde diffusion following moderate to severe depolarization of hippocampal pyramidal neurons. However, it is not clear how hippocampal neurons, which have relatively low firing rates in vivo, achieve the degree of depolarization required to release endocannabinoids. Here it is demonstrated that DSI is not dependent on the occurrence of action potentials in the postsynaptic neuron, but is mediated by depolarization-induced calcium entry via voltage-controlled calcium channels (VCCs). The optimal level of calcium entry, and subsequent DSI, are directly related to the frequency of depolarizing pulses, which differs between immature and adult hippocampus. However, it is shown via modeled spike train inputs that the frequency dependence of DSI is overcome if two or more convergent spike trains from different neurons with normal in vivo firing rates converge and overlap in time. In these modeled circumstances, endocannabinoid-mediated DSI occurs most often when converging synaptic inputs from multiple neurons fire in synchrony to allow temporal summation of local membrane events in postsynaptic cells to exceed threshold for calcium entry. It is therefore possible that such suppression of inhibition would only occur during the time that recipient hippocampal neurons receive multiple coincident excitatory synaptic inputs.