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Article

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
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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MDPI and ACS Style

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. https://doi.org/10.3390/ijms20122913

AMA Style

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. International Journal of Molecular Sciences. 2019; 20(12):2913. https://doi.org/10.3390/ijms20122913

Chicago/Turabian Style

Umehara, Shohei, Xiaoqiu Tan, Yosuke Okamoto, Kyoichi Ono, Akinori Noma, Akira Amano, and Yukiko Himeno. 2019. "Mechanisms Underlying Spontaneous Action Potential Generation Induced by Catecholamine in Pulmonary Vein Cardiomyocytes: A Simulation Study" International Journal of Molecular Sciences 20, no. 12: 2913. https://doi.org/10.3390/ijms20122913

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