scholarly journals Mechanisms Underlying Spontaneous Action Potential Generation Induced by Catecholamine in Pulmonary Vein Cardiomyocytes: A Simulation Study

2019 ◽  
Vol 20 (12) ◽  
pp. 2913 ◽  
Author(s):  
Shohei Umehara ◽  
Xiaoqiu Tan ◽  
Yosuke Okamoto ◽  
Kyoichi Ono ◽  
Akinori Noma ◽  
...  

Cardiomyocytes and myocardial sleeves dissociated from pulmonary veins (PVs) potentially generate ectopic automaticity in response to noradrenaline (NA), and thereby trigger atrial fibrillation. We developed a mathematical model of rat PV cardiomyocytes (PVC) based on experimental data that incorporates the microscopic framework of the local control theory of Ca2+ release from the sarcoplasmic reticulum (SR), which can generate rhythmic Ca2+ release (limit cycle revealed by the bifurcation analysis) when total Ca2+ within the cell increased. Ca2+ overload in SR increased resting Ca2+ efflux through the type II inositol 1,4,5-trisphosphate (IP3) receptors (InsP3R) as well as ryanodine receptors (RyRs), which finally triggered massive Ca2+ release through activation of RyRs via local Ca2+ accumulation in the vicinity of RyRs. The new PVC model exhibited a resting potential of −68 mV. Under NA effects, repetitive Ca2+ release from SR triggered spontaneous action potentials (APs) by evoking transient depolarizations (TDs) through Na+/Ca2+ exchanger (APTDs). Marked and variable latencies initiating APTDs could be explained by the time courses of the α1- and β1-adrenergic influence on the regulation of intracellular Ca2+ content and random occurrences of spontaneous TD activating the first APTD. Positive and negative feedback relations were clarified under APTD generation.

2015 ◽  
Vol 43 (3) ◽  
pp. 410-416 ◽  
Author(s):  
Katja Rietdorf ◽  
Said Masoud ◽  
Fraser McDonald ◽  
Michael J. Sanderson ◽  
Martin D. Bootman

Atrial fibrillation (AF) is the most common form of sustained cardiac arrhythmia. Substantial evidence indicates that cardiomyocytes located in the pulmonary veins [pulmonary vein sleeve cells (PVCs)] cause AF by generating ectopic electrical activity. Electrical ablation, isolating PVCs from their left atrial junctions, is a major treatment for AF. In small rodents, the sleeve of PVCs extends deep inside the lungs and is present in lung slices. Here we present data, using the lung slice preparation, characterizing how spontaneous Ca2+ transients in PVCs affect their capability to respond to electrical pacing. Immediately after a spontaneous Ca2+ transient the cell is in a refractory period and it cannot respond to electrical stimulation. Consequently, we observe that the higher the level of spontaneous activity in an individual PVC, the less likely it is that this PVC responds to electrical field stimulation. The spontaneous activity of neighbouring PVCs can be different from each other. Heterogeneity in the Ca2+ signalling of cells and in their responsiveness to electrical stimuli are known pro-arrhythmic events. The tendency of PVCs to show spontaneous Ca2+ transients and spontaneous action potentials (APs) underlies their potential to cause AF.


1966 ◽  
Vol 50 (2) ◽  
pp. 243-253 ◽  
Author(s):  
Tomio Kanno ◽  
Kojiro Matsuda

Intracellular records were made from fibers in the A-V conducting system of isolated toad hearts. The A-V region was perfused with Ringer's solution of various K and Na concentrations. Resting potential in 2.8 mM [K]o was about 60 mv. Over the range 0.28 to 28 mM, resting potential diminished with increasing [K]o. Spontaneous action potentials appeared when [K]o was increased to 11.2 mM, and when resting potential had fallen to about 40 to 50 mv. Changes in [Na]o over the range 22 to 110 mM had a little effect on resting potential, but there was a linear relation between the peak value of the action potential and log [Na]o Wenckebach periodicity was observed when [Na]o was lowered.


1987 ◽  
Vol 253 (4) ◽  
pp. F778-F781 ◽  
Author(s):  
D. R. Harder ◽  
R. Gilbert ◽  
J. H. Lombard

The goal of this study was to define some of the cellular and ionic mechanisms of smooth muscle cell activation in dog renal arteries exposed to physiological levels of transmural pressure. Isolated interlobular arteries were cannulated and connected to a pressure reservoir to allow manipulation of transmural pressure in 20-mmHg increment steps from 20 to 120 mmHg. As transmural pressure was increased, vascular smooth muscle exhibited a linear depolarization from an average resting potential of -57+/- 2 mV at 20 mmHg to -38+/- 2.4 mV at 120 mmHg. Spontaneous action potentials could often be recorded at pressures greater than 80 mmHg. These appeared to occur primarily at bifurcation points of branching arteries. Vascular smooth muscle depolarization and action potentials occurring in response to increases in transmural pressure were associated with a maintenance of internal diameter of the vessel segments despite increases in transmural pressure in the range between 60 and 120 mmHg. The “pressure-induced” activation of vascular smooth muscle contraction and spontaneous action potentials of small renal arteries at higher transmural pressures were blocked on Ca2+ channel inhibition with verapamil (10(-6) M). These data document a membrane ionic mechanism (probably increased Ca2+ influx) for pressure-induced myogenic activation of isolated renal arteries. It is interesting that the contraction of these vessels occurs over the pressure range in which autoregulation of renal blood flow normally occurs. The physiological significance of these responses needs to be determined.


2008 ◽  
Vol 96 (1-3) ◽  
pp. 132-151 ◽  
Author(s):  
Chang Ahn Seol ◽  
Jun Kim ◽  
Won Tae Kim ◽  
Jeong Mi Ha ◽  
Han Choe ◽  
...  

2019 ◽  
Vol 122 (6) ◽  
pp. 2284-2293 ◽  
Author(s):  
Michael W. Country ◽  
Benjamin F. N. Campbell ◽  
Michael G. Jonz

Horizontal cells (HCs) are interneurons of the outer retina that undergo graded changes in membrane potential during the light response and provide feedback to photoreceptors. We characterized spontaneous Ca2+-based action potentials (APs) in isolated goldfish ( Carassius auratus) HCs with electrophysiological and intracellular imaging techniques. Transient changes in intracellular Ca2+ concentration ([Ca2+]i) were observed with fura-2 and were abolished by removal of extracellular Ca2+ or by inhibition of Ca2+ channels by 50 µM Cd2+ or 100 µM nifedipine. Inhibition of Ca2+ release from stores with 20 µM ryanodine or 50 µM dantrolene abolished Ca2+ transients and increased baseline [Ca2+]i. This increased baseline was prevented by blocking L-type Ca2+ channels with nifedipine, suggesting that Ca2+-induced Ca2+ release from stores may be needed to inactivate membrane Ca2+ channels. Caffeine (3 mM) increased the frequency of Ca2+ transients, and the store-operated channel antagonist 2-aminoethyldiphenylborinate (100 μM) counteracted this effect. APs were detected with voltage-sensitive dye imaging (FluoVolt) and current-clamp electrophysiology. In current-clamp recordings, regenerative APs were abolished by removal of extracellular Ca2+ or in the presence of 5 mM Co2+ or 100 µM nifedipine, and APs were amplified with 15 mM Ba2+. Collectively, our data suggest that during APs Ca2+ enters through L-type Ca2+ channels and that Ca2+ stores (gated by ryanodine receptors) contribute to the rise in [Ca2+]i. This work may lead to further understanding of the possible role APs have in vision, such as transitioning from light to darkness or modulating feedback from HCs to photoreceptors. NEW & NOTEWORTHY Horizontal cells (HCs) are interneurons of the outer retina that provide inhibitory feedback onto photoreceptors. HCs respond to light via graded changes in membrane potential. We characterized spontaneous action potentials in HCs from goldfish and linked action potential generation to a rise in intracellular Ca2+ via plasma membrane channels and ryanodine receptors. Action potentials may play a role in vision, such as transitioning from light to darkness, or in modulating feedback from HCs to photoreceptors.


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