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Epigallocatechin-3-gallate modulates arrhythmogenic activity and calcium homeostasis of left atrium.

Research paper by Jun-Hei JH Chang, Shih-Lin SL Chang, Po-Da PD Hong, Ping-Nan PN Chen, Chih-Hsueng CH Hsu, Yen-Yu YY Lu, Yao-Chang YC Chen

Indexed on: 25 Jan '17Published on: 25 Jan '17Published in: International Journal of Cardiology



Abstract

Atrial fibrillation (AF) is the commonest sustained arrhythmia, and increases the risk of stroke, heart failure, and mortality. Calcium (Ca(2+)) overload and oxidative stress are thought to participate in the pathogenesis of AF. Epigallocatechin-3-gallate (EGCG) has an antioxidative effect and been shown to be beneficial in promoting cardiovascular health. However, it is not clear if EGCG directly modulates the electrophysiological characteristics and Ca(2+) homeostasis of the left atrium (LA).Conventional microelectrodes, whole-cell patch-clamp, and Fluo-3 fluorometric ratio technique were performed using the isolated rabbit LA preparations or isolated single LA cardiomyocytes before and after EGCG treatment. EGCG (0.01, 0.1, 1, and 10μM) which concentration-dependently decreased the APD20 by 13±8%, 25±5%, 31±6%, and 37±5%, APD50 by 9±8%, 22±6%, 32±7%, and 40±4%, and APD90 by 2±12%, 9±8%, 24±10%, and 34±5% in LA preparations. EGCG (0.1μM) decreased the late sodium (Na(+)) current, L-type Ca(2+) current, nickel-sensitive Na(+)-Ca(2+) exchanger current, and transient outward current, but did not change the Na(+) current and ultra-rapid delayed rectifier potassium current in LA cardiomyocytes. EGCG decreased intracellular Ca(2+) transient and sarcoplasmic reticulum Ca(2+) content in LA cardiomyocytes. Furthermore, EGCG decreased isoproterenol (ISO, 1μM)-induced burst firing. KT5823 (1μM) or KN93 (1μM) decreased the incidences of ISO-induced LA burst firing, which became lower with EGCG treatment. H89 (10μM) and KN92 (1μM) did not suppress the incidence of ISO-induced LA burst firing. However, EGCG decreased the incidences of ISO-induced LA burst firing in the presence of H89 or KN92.EGCG directly regulates LA electrophysiological characteristics and Ca(2+) homeostasis, and suppresses ISO-induced atrial arrhythmogenesis through inhibiting Ca(2+)/calmodulin or cGMP-dependent protein kinases.