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Open AccessArticle

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

1
Department of Bioinformatics, College of Life Sciences, Ritsumeikan University, Shiga 525-8577, Japan
2
Institute of Cardiovascular Research, Southwest Medical University, Luzhou 640000, China
3
Department of Cell Physiology, Graduate School of Medicine, Akita University, Akita 010-8543, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(12), 2913; https://doi.org/10.3390/ijms20122913
Received: 11 May 2019 / Revised: 11 June 2019 / Accepted: 12 June 2019 / Published: 14 June 2019
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Abstract

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. View Full-Text
Keywords: rat pulmonary vein cardiac myocyte; automaticity; α1- and β1-adrenoceptor; InsP3R; IP3 rat pulmonary vein cardiac myocyte; automaticity; α1- and β1-adrenoceptor; InsP3R; IP3
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Umehara, S.; Tan, X.; Okamoto, Y.; Ono, K.; Noma, A.; Amano, A.; Himeno, Y. Mechanisms Underlying Spontaneous Action Potential Generation Induced by Catecholamine in Pulmonary Vein Cardiomyocytes: A Simulation Study. Int. J. Mol. Sci. 2019, 20, 2913.

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