scholarly journals Spiking resonances in models with the same slow resonant and fast amplifying currents but different subthreshold dynamic properties

2017 ◽  
Author(s):  
Horacio G. Rotstein
Keyword(s):  
Time Scales ◽  
Frequency Band ◽  
Dynamic Properties ◽  
Sodium Current ◽  
Ionic Currents ◽  
Voltage Response ◽  
Subthreshold Oscillations ◽  
Subthreshold Resonance ◽  
Subthreshold Voltage ◽  
Underlying Mechanisms

AbstractThe generation of spiking resonances in neurons (preferred spiking responses to oscillatory inputs) requires the interplay of the intrinsic ionic currents that operate at the subthreshold voltage regime and the spiking mechanism. Combinations of the same types of ionic currents in different parameter regimes may give rise to different types of nonlinearities in the voltage equation (e.g., parabolic- and cubic-like), generating subthreshold oscillations patterns with different properties. We investigate the spiking resonant properties of conductance-based models that are biophysically equivalent at the subthreshold level (same ionic currents), but functionally different (parabolic- and cubic-like). As a case study we consider a model having a persistent sodium current and a hyperpolarization-activated (h-) current. We unfold the concept of spiking resonance into evoked and output spiking resonance. The former focuses on the input frequencies that are able to generate spikes, while the latter focuses on the output spiking frequencies regardless of the input frequency that generated these spikes. A cell can exhibit one or both types of resonance. We also measure spiking phasonance, which is an extension of subthreshold phasonance to the spiking regime. The subthreshold resonant properties of both types of models are communicated to the spiking regime for low enough input amplitudes as the voltage response for the subthreshold resonant frequency band raises above threshold. For higher input amplitudes evoked spiking resonance is no longer present, but output spiking resonance is present primarily in the parabolic-like model, while the cubic-like model shows a better 1:1 entrainment. We use dynamical systems tools to explain the underlying mechanisms and the mechanistic differences between the resonance types. Our results show that the effective time scales that operate at the subthreshold regime to generate intrinsic subthreshold oscillations, mixed-mode oscillations and subthreshold resonance do not necessarily determine the existence of a preferred spiking response to oscillatory inputs in the same frequency band. The results discussed in this paper highlight both the complexity of the suprathreshold responses to oscillatory inputs in neurons having resonant and amplifying currents with different time scales and the fact that the identity of the participating ionic currents is not enough to predict the resulting patterns, but additional dynamic information, captured by the geometric properties of the phase-space diagram, is needed.

scholarly journals Characterization of Direct Perturbations on Voltage-Gated Sodium Current by Esaxerenone, a Nonsteroidal Mineralocorticoid Receptor Blocker

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 549
Author(s):  
Wei-Ting Chang ◽  
Sheng-Nan Wu
Keyword(s):  
Mineralocorticoid Receptor ◽  
Sodium Current ◽  
Ionic Currents ◽  
Antagonistic Effect ◽  
Gh3 Cells ◽  
Excitable Cells ◽  
Voltage Gated ◽  
Ic50 Value ◽  
Low Threshold

Esaxerenone (ESAX; CS-3150, Minnebro®) is known to be a newly non-steroidal mineralocorticoid receptor (MR) antagonist. However, its modulatory actions on different types of ionic currents in electrically excitable cells remain largely unanswered. The present investigations were undertaken to explore the possible perturbations of ESAX on the transient, late and persistent components of voltage-gated Na+ current (INa) identified from pituitary GH3 or MMQ cells. GH3-cell exposure to ESAX depressed the transient and late components of INa with varying potencies. The IC50 value of ESAX required for its differential reduction in peak or late INa in GH3 cells was estimated to be 13.2 or 3.2 μM, respectively. The steady-state activation curve of peak INa remained unchanged during exposure to ESAX; however, recovery of peak INa block was prolonged in the presence 3 μM ESAX. In continued presence of aldosterone (10 μM), further addition of 3 μM ESAX remained effective at inhibiting INa. ESAX (3 μM) potently reversed Tef-induced augmentation of INa. By using isosceles-triangular ramp pulse with varying durations, the amplitude of persistent INa measured at high or low threshold was enhanced by the presence of tefluthrin (Tef), in combination with the appearance of the figure-of-eight hysteretic loop; moreover, hysteretic strength of the current was attenuated by subsequent addition of ESAX. Likewise, in MMQ lactotrophs, the addition of ESAX also effectively decreased the peak amplitude of INa along with the increased current inactivation rate. Taken together, the present results provide a noticeable yet unidentified finding disclosing that, apart from its antagonistic effect on MR receptor, ESAX may directly and concertedly modify the amplitude, gating properties and hysteresis of INa in electrically excitable cells.

Multiscale Joint Symbolic Transfer Entropy for Quantification of Causal Interactions Between Heart Rate and Blood Pressure Variability Under Postural Stress

2015 ◽  
Vol 14 (03) ◽  
pp. 1550031 ◽  
Author(s):  
A. Singh ◽  
B. S. Saini ◽  
D. Singh
Keyword(s):  
Blood Pressure ◽  
Time Delay ◽  
Time Scales ◽  
Frequency Band ◽  
Supine Position ◽  
Time Scale ◽  
Upright Position ◽  
Multiple Time Scales ◽  
Multiple Time ◽  
Symbolic Transfer Entropy

In this paper, joint symbolic transfer entropy (JSTE) is explored to quantify causal interactions between systolic blood pressure (SBP) and RR intervals (peak-to-peak distance between consecutive R-peaks) at multiple time scales. SBP→RR coupling (C s-r ) and RR→SBP coupling (C r-s ) coupling is analyzed at multiple time scales and delays. The ability of the approach based on JSTE to detect SBP–RR causal coupling is tested on 42 healthy subjects in supine and upright position along with 21 subjects of EUROBAVAR dataset. In addition, lack of causal coupling from SBP to RR was assessed on 20 post-acute myocardial infarction (AMI) patients. Results demonstrate that (i) standard deviation (SD) of RR interval series and SBP series decreases with time scale τ = 1 to 10 for all types of subjects. (ii) SD in supine is more than that of upright position at each time scale irrespective of types of subjects. (iii) JSTE decreases with time delay for healthy and AMI patients but does not follow decreasing trend for baroflex sensitivity BRS failure patients. (iv) JSTE in supine position is more than that of upright position irrespective of time delay. (v) JSTE decreases with time scale for healthy and AMI patients but does not follow decreasing trend for BRS failure patients. (vi) JSTE in supine position is more than that of upright position only at finer scales. (vii) Enhanced feed-forward (FF) coupling and suppressed feedback (FB) coupling found at supine position within low frequency band (0.04–0.15 Hz) as well as high frequency band (0.151–0.4 Hz) indicated prevalence on non-baroreflex mechanisms. (viii) FB coupling recovered in the upright position which was stronger than FF coupling. Upon comparison with cross conditional entropy (CCE), it is found that JSTE provides more significant differences between supine and upright position.

scholarly journals Temporal filters in response to presynaptic spike trains: Interplay of cellular, synaptic and short-term plasticity time scales

2021 ◽  
Author(s):  
Yugarshi Mondal ◽  
Rodrigo F. O. Pena ◽  
Horacio G. Rotstein
Keyword(s):  
Time Scales ◽  
Dynamic Properties ◽  
Information Filtering ◽  
Distribution Patterns ◽  
Building Blocks ◽  
Spike Trains ◽  
Short Term ◽  
Short Term Plasticity ◽  
Important Player ◽  
Presynaptic Spike

Temporal filters, the ability of postsynaptic neurons to preferentially select certain presynaptic input patterns, have been shown to be associated with the notion of information filtering and coding of sensory inputs. Their properties can be dynamically characterized as the transient responses to periodic presynaptic inputs. Short-term plasticity (STP) has been proposed to be an important player in the generation of temporal filters, but the response of postsynaptic neurons to presynaptic inputs depends on a collection of time scales in addition to STP's, which conspire to create temporal filters: the postsynaptic time scales generated by the cellular intrinsic currents and the presynaptic time scales captured by the ISI distribution patterns. The mechanisms by which these time scales and the processes giving rise to them interact to produce temporal filters in response to presynaptic input spike trains are not well understood. We carry out a systematic modeling and computational analysis to understand how the postsynaptic low-, high- and band-pass temporal filters are generated in response to periodic presynaptic spike trains in the presence STP, and how the dynamic properties of these filters depend on the interplay of a hierarchy of processes: arrival of the presynaptic spikes, the activation of STP and its effect on the synaptic connection efficacy, and the response of the postsynaptic cell. The time scales associated with each of these processes operate at the short-term, single-event level (they are activated at the arrival of each presynaptic spike) and collectively produce the long-term time scales that determine the shape and properties of the filters. We develop a series of mathematical tools to address these issues for a relatively simple model where depression and facilitation interact only at the level of the synaptic efficacy change as time progresses and we extend our results and tools to account for more complex models that involve interactions at the STP level and multiple STP time scales. We use these tools to understand the mechanisms of generation of temporal filters in the postsynaptic cells in terms of the properties and dynamics of the interacting building blocks.

Dual actions of caffeine on voltage-dependent currents and intracellular calcium in taste receptor cells

2002 ◽  
Vol 283 (1) ◽  
pp. R115-R129 ◽  
Author(s):  
Fang-Li Zhao ◽  
Shao-Gang Lu ◽  
Scott Herness
Keyword(s):  
Intracellular Calcium ◽  
Imaging Techniques ◽  
Sodium Current ◽  
Taste Receptor ◽  
Input Resistance ◽  
Ionic Currents ◽  
Receptor Cells ◽  
Voltage Dependent ◽  
Transduction Mechanisms ◽  
Taste Receptor Cells

Although the numerous stimuli representing the taste quality of bitterness are known to be transduced through multiple mechanisms, recent studies have suggested an unpredicted complexity of the transduction pathways for individual bitter stimuli. To investigate this notion more thoroughly, a single prototypic bitter stimulus, caffeine, was studied by using patch-clamp and ratiometric imaging techniques on dissociated rat taste receptor cells. At behaviorally relevant concentrations, caffeine produced strong inhibition of outwardly and inwardly rectifying potassium currents. Caffeine additionally inhibited calcium current, produced a weaker inhibition of sodium current, and was without effect on chloride current. Consistent with its effects on voltage-dependent currents, caffeine caused a broadening of the action potential and an increase of the input resistance. Caffeine was an effective stimulus for elevation of intracellular calcium. This elevation was concentration dependent, independent of extracellular calcium or ryanodine, and dependent on intracellular stores as evidenced by thapsigargin treatment. These dual actions on voltage-activated ionic currents and intracellular calcium levels suggest that a single taste stimulus, caffeine, utilizes multiple transduction mechanisms.

Frequency Selectivity of Layer II Stellate Cells in the Medial Entorhinal Cortex

2002 ◽  
Vol 88 (5) ◽  
pp. 2422-2429 ◽  
Author(s):  
Julie S. Haas ◽  
John A. White
Keyword(s):  
Entorhinal Cortex ◽  
Stellate Cells ◽  
Mechanistic Explanation ◽  
Input Power ◽  
Total Power ◽  
Frequency Content ◽  
Medial Entorhinal Cortex ◽  
Subthreshold Oscillations ◽  
Subthreshold Resonance

Electrophysiologically, stellate cells (SCs) from layer II of the medial entorhinal cortex (MEC) are distinguished by intrinsic 4- to 12-Hz subthreshold oscillations. These oscillations are thought to impose a pattern of slow periodic firing that may contribute to the parahippocampal theta rhythm in vivo. Using stimuli with systematically differing frequency content, we examined supra- and subthreshold responses in SCs with the goal of understanding how their distinctive characteristics shape these responses. In reaction to repeated presentations of identical, pseudo-random stimuli, the reliability (repeatability) of the spiking response in SCs depends critically on the frequency content of the stimulus. Reliability is optimal for stimuli with a greater proportion of power in the 4- to 12-Hz range. The simplest mechanistic explanation of these results is that rhythmogenic subthreshold membrane mechanisms resonate with inputs containing significant power in the 4- to 12-Hz band, leading to larger subthreshold excursions and thus enhanced reliability. However, close examination of responses rules out this explanation: SCs do show clear subthreshold resonance (i.e., selective amplification of inputs with particular frequency content) in response to sinusoidal stimuli, while simultaneously showing a lack of subthreshold resonance in response to the pseudo-random stimuli used in reliability experiments. Our results support a model with distinctive input-output relationships under subthreshold and suprathreshold conditions. For suprathreshold stimuli, SC spiking seems to best reflect the amount of input power in the theta (4–12 Hz) frequency band. For subthreshold stimuli, we hypothesize that the magnitude of subthreshold theta-range oscillations in SCs reflects the total power, across all frequencies, of the input.

Depression of excitability by sphingosine 1-phosphate in rat ventricular myocytes

1998 ◽  
Vol 275 (6) ◽  
pp. H2291-H2299 ◽  
Author(s):  
Karen L. MacDonell ◽  
David L. Severson ◽  
Wayne R. Giles
Keyword(s):  
Action Potential ◽  
Ventricular Myocytes ◽  
Sodium Current ◽  
Potassium Conductance ◽  
Ionic Currents ◽  
Stimulus Current ◽  
Muscle Action Potential ◽  
Action Potential Waveform ◽  
Sphingosine 1 Phosphate ◽  
Electrophysiological Effects

Sphingosine 1-phosphate (S-1- P) is a bioactive sphingolipid that is released from activated platelets. Extracellular S-1- P augments an inwardly rectifying potassium conductance in cultured atrial preparations, but the electrophysiological effects of this compound in the ventricle are unknown. The electrophysiological effects of S-1- P were examined in single myocytes from rat ventricular muscle. Action potential waveforms and underlying ionic currents in the presence and absence of 3 μM S-1- P (1–6 min) were recorded. S-1- P increased the minimum stimulus current needed to elicit an action potential by ∼100 pA. Pertussis toxin or preexposure to S-1- P did not alter this effect. The action potential waveform was unchanged by S-1- P. The inward sodium current ( I Na) was examined in a range of membrane potentials just negative to the potential for firing an action potential. S-1- P reversibly inhibited peak I Na by ∼50 pA, whereas the inward rectifier potassium current was not significantly changed. The results of this study suggest that S-1- P inhibits rat ventricular excitability by reducing I Na.

PROPERTIES OF 185TAGE-ACTIVATED IONIC CURRENTS IN CELLS FROM THE BRAINS OF THE TRICLAD FLATWORM BDELLOURA CANDIDA

1993 ◽  
Vol 185 (1) ◽  
pp. 267-286
Author(s):  
K. L. Blair ◽  
P. A. V. Anderson
Keyword(s):  
Cultured Cells ◽  
Sodium Current ◽  
Cell Voltage ◽  
Ionic Currents ◽  
Sodium Currents ◽  
Channel Evolution ◽  
Major Stage ◽  
Fast Transient ◽  
State Component

Cells were dispersed from the brains of the triclad flatworm Bdelloura candida and maintained in primary culture for up to 2 weeks. Cultured cells assumed a variety of morphologies consistent with those of neurones in vivo. Whole-cell voltage-clamp recordings from cultured cells revealed that these cells possess a variety of ionic currents, including a fast transient sodium current, a calcium current and several potassium currents. The sodium current does not inactivate completely but instead decays to a steady-state component which has the same physiology and pharmacology as the fast transient component, suggesting that the two components are carried by the same population of channels. The physiology and pharmacology of these various currents were not remarkable save for the fact that, contrary to earlier reports, all sodium currents examined were sensitive to tetrodotoxin (TTX). These animals are, therefore, the lowest animals known to possess TTX-sensitive sodium currents and, as such, represent a major stage in sodium channel evolution.

scholarly journals The Na+/K+ pump is an important modulator of refractoriness and rotor dynamics in human atrial tissue

2012 ◽  
Vol 302 (5) ◽  
pp. H1146-H1159 ◽  
Author(s):  
Carlos Sánchez ◽  
Alberto Corrias ◽  
Alfonso Bueno-Orovio ◽  
Mark Davies ◽  
Jonathan Swinton ◽  
...  
Keyword(s):  
Sodium Current ◽  
Ionic Currents ◽  
Pump Current ◽  
Rotor Dynamics ◽  
Dominant Frequency ◽  
Systematic Analysis ◽  
Electrophysiological Properties ◽  
Atrial Electrophysiology ◽  
Before And After

Pharmacological treatment of atrial fibrillation (AF) exhibits limited efficacy. Further developments require a comprehensive characterization of ionic modulators of electrophysiology in human atria. Our aim is to systematically investigate the relative importance of ionic properties in modulating excitability, refractoriness, and rotor dynamics in human atria before and after AF-related electrical remodeling (AFER). Computer simulations of single cell and tissue atrial electrophysiology were conducted using two human atrial action potential (AP) models. Changes in AP, refractory period (RP), conduction velocity (CV), and rotor dynamics caused by alterations in key properties of all atrial ionic currents were characterized before and after AFER. Results show that the investigated human atrial electrophysiological properties are primarily modulated by maximal value of Na+/K+ pump current ( GNaK) as well as conductances of inward rectifier potassium current ( GK1) and fast inward sodium current ( GNa). GNaK plays a fundamental role through both electrogenic and homeostatic modulation of AP duration (APD), APD restitution, RP, and reentrant dominant frequency (DF). GK1 controls DF through modulation of AP, APD restitution, RP, and CV. GNa is key in determining DF through alteration of CV and RP, particularly in AFER. Changes in ionic currents have qualitatively similar effects in control and AFER, but effects are smaller in AFER. The systematic analysis conducted in this study unravels the important role of the Na+/K+ pump current in determining human atrial electrophysiology.

scholarly journals Cytosolic calcium changes affect the incidence of early afterdepolarizations in canine ventricular myocytes

2015 ◽  
Vol 93 (7) ◽  
pp. 527-534 ◽  
Author(s):  
Balázs Horváth ◽  
Bence Hegyi ◽  
Kornél Kistamás ◽  
Krisztina Váczi ◽  
Tamás Bányász ◽  
...  
Keyword(s):  
Action Potentials ◽  
Ventricular Myocytes ◽  
Sodium Current ◽  
Cytosolic Calcium ◽  
Delayed Rectifier ◽  
Isolated Cells ◽  
Experimental Conditions ◽  
Early Afterdepolarizations ◽  
Late Sodium Current ◽  
Underlying Mechanisms

This study was designed to investigate the influence of cytosolic Ca2+ levels ([Ca2+]i) on action potential duration (APD) and on the incidence of early afterdepolarizations (EADs) in canine ventricular cardiomyocytes. Action potentials (AP) of isolated cells were recorded using conventional sharp microelectrodes, and the concomitant [Ca2+]i was monitored with the fluorescent dye Fura-2. EADs were evoked at a 0.2 Hz pacing rate by inhibiting the rapid delayed rectifier K+ current with dofetilide, by activating the late sodium current with veratridine, or by activating the L-type calcium current with BAY K8644. These interventions progressively prolonged the AP and resulted in initiation of EADs. Reducing [Ca2+]i by application of the cell-permeant Ca2+ chelator BAPTA-AM lengthened the AP at 1.0 Hz if it was applied alone, in the presence of veratridine, or in the presence of BAY K8644. However, BAPTA-AM shortened the AP if the cells were pretreated with dofetilide. The incidence of the evoked EADs was strongly reduced by BAPTA-AM in dofetilide, moderately reduced in veratridine, whereas EAD incidence was increased by BAPTA-AM in the presence of BAY K8644. Based on these experimental data, changes in [Ca2+]i have marked effects on APD as well as on the incidence of EADs; however, the underlying mechanisms may be different, depending on the mechanism of EAD generation. As a consequence, reduction of [Ca2+]i may eliminate EADs under some, but not all, experimental conditions.

scholarly journals Effect of Oxaliplatin on Voltage-Gated Sodium Channels in Peripheral Neuropathic Pain

Processes ◽  
2020 ◽  
Vol 8 (6) ◽  
pp. 680 ◽  
Author(s):  
Woojin Kim
Keyword(s):  
Neuropathic Pain ◽  
Action Potential ◽  
Sodium Channels ◽  
Sodium Current ◽  
Voltage Response ◽  
Treatment Schedule ◽  
Voltage Gated ◽  
Peripheral Neurons ◽  
Voltage Gated Sodium Channels ◽  
Current Voltage

Oxaliplatin is a chemotherapeutic drug widely used to treat various types of tumors. However, it can induce a serious peripheral neuropathy characterized by cold and mechanical allodynia that can even disrupt the treatment schedule. Since the approval of the agent, many laboratories, including ours, have focused their research on finding a drug or method to decrease this side effect. However, to date no drug that can effectively reduce the pain without causing any adverse events has been developed, and the mechanism of the action of oxaliplatin is not clearly understood. On the dorsal root ganglia (DRG) sensory neurons, oxaliplatin is reported to modify their functions, such as the propagation of the action potential and induction of neuropathic pain. Voltage-gated sodium channels in the DRG neurons are important, as they play a major role in the excitability of the cell by initiating the action potential. Thus, in this small review, eight studies that investigated the effect of oxaliplatin on sodium channels of peripheral neurons have been included. Its effects on the duration of the action potential, peak of the sodium current, voltage–response relationship, inactivation current, and sensitivity to tetrodotoxin (TTX) are discussed.

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