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

Background: Atrial fibrillation (AF) is the commonest sustained arrhythmia, and increases the risk of stroke, heart failure, and mortality. Calcium (Ca) 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 homeostasis of the left atrium (LA).

Methods And Results: 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 APD by 13±8%, 25±5%, 31±6%, and 37±5%, APD by 9±8%, 22±6%, 32±7%, and 40±4%, and APD 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 current, nickel-sensitive Na-Ca 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 transient and sarcoplasmic reticulum Ca 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.

Conclusion: EGCG directly regulates LA electrophysiological characteristics and Ca homeostasis, and suppresses ISO-induced atrial arrhythmogenesis through inhibiting Ca/calmodulin or cGMP-dependent protein kinases.