Dataset Information

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

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 (AP_TDs). Marked and variable latencies initiating AP_TDs could be explained by the time courses of the ?1- and ?1-adrenergic influence on the regulation of intracellular Ca²⁺ content and random occurrences of spontaneous TD activating the first AP_TD. Positive and negative feedback relations were clarified under AP_TD generation.

SUBMITTER: Umehara S

PROVIDER: S-EPMC6628582 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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

Umehara Shohei S Tan Xiaoqiu X Okamoto Yosuke Y Ono Kyoichi K Noma Akinori A Amano Akira A Himeno Yukiko Y

International journal of molecular sciences 20190614 12

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 Ca<sup>2+</sup> release from the sarcoplasmic reticulum (SR), which can generate rhythmic Ca<sup>2+</sup> release (limit cycle revealed by ...[more]

PMID: 31207916

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Dataset Information

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

Publications

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

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