Effect Of (−)-epigallocatechin Gallate (EGCG), A Green Tea Extract, On Excitation-contraction Coupling Of Murine Cardiomyocytes

Abstract

Background: Polyphenolic compounds, green tea, reportedly have protective benefit for cardiovascular disease, but the mechanism(s) are unknown. We have recently found that green tea extracts such as (-)-epigallocatechin gallate(EGCG) bind to skeletal and cardiac ryanodine receptor(RyR) Ca2+-release channels. Here we examined the effect of EGCG(1μM, 100nM, 10nM) on cell shortening and Ca2+ kinetics in field-stimulated murine ventricular cardiomyocytes loaded with Fura-2AM and on cardiac RyR channels incorporated in lipid bilayers. Results: EGCG at 10 nM already maximally increased myocytes fractional shortening(%FS): ECGC 5.6±0.7, N=19, vs. Vehicle, 2.2±0.3, N=25, p 30-fold prolonging mean open time 15-fold without altering unitary conductance. EGCG did not alter SR Ca2+ loading capacity in the presence of RyR channel blocker ruthenium red. Taken together, these data suggest that EGCG enhances contractility of intact myocytes via its action on RyR channels. SR Ca2+ depletion is prevented by EGCG's concomitant inhibition of the NCX. Conclusions: EGCG potently modulates cardiac excitation contraction coupling by acting on RyR and possibly on L-type Ca2+-channel and NaCa exchanger. Supported by R01HL71670, R01HL88635, and R01AR43140