scholarly journals Investigation of the Extracellular Calcium Effects on Action Potential using the Most Recent Human Ventricular Cell Models

2020 ◽  
Author(s):  
Chiara Bartolucci ◽  
Michelangelo Paci ◽  
Stefano Severi
Keyword(s):  
Action Potential ◽  
Extracellular Calcium ◽  
Cell Models ◽  
Ventricular Cell ◽  
Calcium Effects

Action potential propagation through embryonic dorsal root ganglion cells in culture. II. Decrease of conduction reliability during repetitive stimulation

1994 ◽  
Vol 72 (2) ◽  
pp. 634-643 ◽  
Author(s):  
C. Luscher ◽  
J. Streit ◽  
P. Lipp ◽  
H. R. Luscher
Keyword(s):  
Dorsal Root Ganglion ◽  
Action Potential ◽  
Intracellular Calcium ◽  
Dorsal Root ◽  
Channel Blocker ◽  
Extracellular Calcium ◽  
Repetitive Stimulation ◽  
Calcium Currents ◽  
Double Pulse ◽  
Extracellular Potassium

1. The reliability of the propagation of action potentials (AP) through dorsal root ganglion (DRG) cells in embryonic slice cultures was investigated during repetitive stimulation at 1–20 Hz. Membrane potentials of DRG cells were recorded intracellularly while the axons were stimulated by an extracellular electrode. 2. In analogy to the double-pulse experiments reported previously, either one or two types of propagation failures were recorded during repetitive stimulation, depending on the cell morphology. In contrast to the double-pulse experiments, the failures appeared at longer interpulse intervals and usually only after several tens of stimuli with reliable propagation. 3. In the period with reliable propagation before the failures, a decrease in the conduction velocity and in the amplitude of the afterhyperpolarization (AHP), an increase in the total membrane conductance, and the disappearance of the action potential “shoulder” were observed. 4. The reliability of conduction during repetitive stimulation was improved by lowering the extracellular calcium concentration or by replacing the extracellular calcium by strontium. The reliability of conduction decreased by the application of cadmium, a calcium channel blocker, 4-amino pyridine, a fast potassium channel blocker, or apamin or muscarine, the blockers of calcium-dependent potassium channels. The reliability of conduction was not effected by blocking the sodium potassium pump with ouabain or by replacing extracellular sodium with lithium. 5. In the period with reliable propagation cadmium, apamin, and muscarine reduced the amplitude of the AHP. The shoulder of the action potential was more pronounced and not sensitive to repetitive stimulation when extracellular calcium was replaced by strontium. It disappeared when cadmium was applied. 6. In DRG somata changes of the intracellular Ca2+ concentration were monitored by measuring the fluorescence of the Ca2+ indicator Fluo-3 with a laser-scanning confocal microscope. During repetitive stimulation, an accumulation of intracellular calcium occurred that recovered very slowly (tens of seconds) after the AP trains. 7. Computer model simulations performed in analogy to the experimental protocols produced conduction failures during repetitive stimulation only when the calcium currents during the APs were reduced. 8. From these findings it is concluded that conduction failures during repetitive stimulation are dependent on an accumulation of intracellular calcium leading to an inactivation of calcium currents, combined with small contributions of an accumulation of extracellular potassium and a summation of slow potassium conductances.

scholarly journals Action potential conduction between a ventricular cell model and an isolated ventricular cell

1996 ◽  
Vol 70 (1) ◽  
pp. 281-295 ◽  
Author(s):  
R. Wilders ◽  
R. Kumar ◽  
R.W. Joyner ◽  
H.J. Jongsma ◽  
E.E. Verheijck ◽  
...  
Keyword(s):  
Action Potential ◽  
Cell Model ◽  
Ventricular Cell ◽  
Ventricular Cell Model

The ex-vivo effects of thyroid status and extracellular calcium concentration on rat atrial and ventricular electrophysiology

1988 ◽  
Vol 66 (1) ◽  
pp. 90-94 ◽  
Author(s):  
R. W. Gristwood ◽  
A. L. Rothaul
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Calcium Concentration ◽  
Ex Vivo ◽  
Additional Treatment ◽  
Extracellular Calcium ◽  
Krebs Solution ◽  
Thyroid Status ◽  
Extracellular Calcium Concentration ◽  
Atrial Electrophysiology

The purpose of this study was to explore the relationship between the thyroid status and both ventricular and atrial electrophysiology in the rat. The study was extended to consider the effects of altering the extracellular calcium concentration. The work was performed in two sections. First, hypothyroid animals were compared with euthyroid (untreated animals); second, hypothyroid animals were compared with hyperthyroid animals. Rats were rendered hypothyroid by pretreatment with the goitrogen methimazole and hyperthyroid by additional treatment with triiodothyronine. Action potential recordings were obtained using standard microelectrode techniques. Action potential measurements were made initially in a Krebs solution to which had been added 2.55 mM calcium (higher Ca Krebs solution) and at the end of each experiment after stabilization with Krebs solution to which had been added 1.28 mM calcium (lower Ca Krebs solution). Assessment of the change in action potential duration on transition from higher to lower Ca Krebs solution revealed that the euthyroid preparations demonstrated less prolongation of action potential duration than the hypothyroid group, and the hyperthyroid group showed hardly any response to reduction in calcium concentration.

scholarly journals Isoprenaline: A Potential Contributor in Sick Sinus Syndrome—Insights from a Mathematical Model of the Rabbit Sinoatrial Node

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Xiang Li ◽  
Ji-qian Zhang ◽  
Jian-wei Shuai
Keyword(s):  
Action Potential ◽  
Sinoatrial Node ◽  
Sick Sinus Syndrome ◽  
Surrounding Tissue ◽  
Pacemaker Activity ◽  
Histological Structure ◽  
Cell Models ◽  
Peripheral Cell ◽  
Positive Effects ◽  
Rabbit Sinoatrial Node

The mechanism of isoprenaline exerting its effects on cardiac pacemaking and driving in sick sinus syndrome is controversial and unresolved. In this paper, mathematical models for rabbit sinoatrial node cells were modified by incorporating equations for the known dose-dependent actions of isoprenaline on various ionic channel currents, the intracellular Ca2+transient, andiNachanges induced by SCN5A gene mutations; the cell models were also incorporated into an intact SAN-atrium model of the rabbit heart that is based on both heterogeneities of the SAN electrophysiology and histological structure. Our results show that, in both central and peripheral cell models, isoprenaline could not only shorten the action potential duration, but also increase the amplitude of action potential. The mutation impaired the SAN pacemaking. Simulated vagal nerve activity amplified the bradycardic effects of the mutation. However, in tissue case, the pacemaker activity may show temporal, spatial, or even spatiotemporal cessation caused by the mutation. Addition of isoprenaline could significantly diminish the bradycardic effect of the mutation and the SAN could restart pacing and driving the surrounding tissue. Positive effects of isoprenaline may primarily be attributable to an increase iniNaandiCa,Twhich were reduced by the mutation.

Role of voltage oscillations in the automaticity of sheep cardiac Purkinje fibers

1995 ◽  
Vol 73 (8) ◽  
pp. 1165-1180 ◽  
Author(s):  
Peter A. Spiegler ◽  
Mario Vassalle
Keyword(s):  
Action Potential ◽  
Spontaneous Activity ◽  
Oscillatory Potentials ◽  
Extracellular Calcium ◽  
Calcium Overload ◽  
Spontaneous Discharge ◽  
Extracellular Potassium ◽  
Purkinje Fibers ◽  
Diastolic Depolarization

The role of oscillatory potentials occurring near the threshold for the fast sodium current (ThVos) in the induction of spontaneous and repetitive activity was studied in sheep Purkinje fibers superfused in vitro. In low extracellular potassium concentration, the steepness and amplitude of diastolic depolarization increased and ThVos appeared during quiescence. ThVos amplitude increased progressively until its depolarizing phase reached the threshold potential for the initiation of the action potential. Drive increased the amplitude of diastolic depolarization and of ThVos, and longer drives induced faster and longer-lasting repetitive activity ("overdrive excitation"). In quiescent fibers, barium depolarized the resting membrane and initiated spontaneous discharge through ThVos. Acetylcholine had similar actions. Cesium hyperpolarized the membrane, thereby suppressing ThVos and related spontaneous activity. Tetrodotoxin and lidocaine also suppressed ThVos, but not the driven action potentials. In low extracellular potassium plus high extracellular calcium concentrations, drive induced ThVos as well as the oscillatory potentials related to calcium overload (Vos), but caused overdrive excitation through ThVos, even when caffeine was present. We conclude from our results that in Purkinje "dominant" pacemaker fibers (i) diastolic depolarization initiates spontaneous activity by attaining the threshold for the upstroke of the action potential through the depolarizing phase of a ThVos; (ii) the depolarizing phase of ThVos is caused by a tetrodotoxin-sensitive Na+ component; (iii) ThVos is voltage dependent in that a small depolarization of the resting membrane induces it and a small hyperpolarization suppresses it; (iv) ThVos can induce overdrive excitation; and (v) ThVos occurs in the absence of calcium overload and has distinguishing characteristics from the Vos induced by calcium overload.Key words: automaticity, overdrive excitation, barium, acetylcholine, cesium, tetrodotoxin, lidocaine, high extracellular calcium, low extracellular potassium.

scholarly journals Calcium stores regulate excitability in cultured rat hippocampal neurons

2018 ◽  
Vol 120 (5) ◽  
pp. 2694-2705 ◽  
Author(s):  
Menahem Segal
Keyword(s):  
Action Potential ◽  
Hippocampal Neurons ◽  
Extracellular Calcium ◽  
Calcium Stores ◽  
Sk Channels ◽  
Central Neurons ◽  
Action Potential Threshold ◽  
Potential Threshold ◽  
Small Conductance ◽  
Cultured Hippocampal Neurons

Extracellular calcium ions support synaptic activity but also reduce excitability of central neurons. In the present study, the effect of calcium on excitability was explored in cultured hippocampal neurons. CaCl2 injected by pressure in the vicinity of a neuron that is bathed only in MgCl2 as the main divalent cation caused a depolarizing shift in action potential threshold and a reduction in excitability. This effect was not seen if the intracellular milieu consisted of Cs+ instead of K-gluconate as the main cation or when it contained ruthenium red, which blocks release of calcium from stores. The suppression of excitability by calcium was mimicked by caffeine, and calcium store antagonists cyclopiazonic acid or thapsigargin blocked this action. Neurons taken from synaptopodin-knockout mice show significantly reduced efficacy of calcium modulation of action potential threshold. Likewise, in Orai1 knockdown cells, calcium is less effective in modulating excitability of neurons. Activation of small-conductance K (SK) channels increased action potential threshold akin to that produced by calcium ions, whereas blockade of SK channels but not big K channels reduced the threshold for action potential discharge. These results indicate that calcium released from stores may suppress excitability of central neurons. NEW & NOTEWORTHY Extracellular calcium reduces excitability of cultured hippocampal neurons. This effect is mediated by calcium-gated potassium currents, possibly small-conductance K channels. Release of calcium from internal stores mimics the effect of extracellular calcium. It is proposed that calcium stores modulate excitability of central neurons.

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