Resveratrol Attenuates the Na+-Dependent Intracellular Ca2+ Overload by Inhibiting H2O2-Induced Increase in Late Sodium Current in Ventricular Myocytes

Abstract

Background/Aims: Resveratrol has been demonstrated to be protective in the cardiovascular system. The aim of this study was to assess the effects of resveratrol on hydrogen peroxide (H2O2)-induced increase in late sodium current (INa.L) which augmented the reverse Na+-Ca2+ exchanger current (INCX), and the diastolic intracellular Ca2+ concentration in ventricular myocytes. Methods: INa.L, INCX, L-type Ca2+ current (ICa.L) and intracellular Ca2+ properties were determined using whole-cell patch-clamp techniques and dual-excitation fluorescence photomultiplier system (IonOptix), respectively, in rabbit ventricular myocytes. Results: Resveratrol (10, 20, 40 and 80 μM) decreased INa.L in myocytes both in the absence and presence of H2O2 (300 μM) in a concentration dependent manner. Ranolazine (3-9 μM) and tetrodotoxin (TTX, 4 μM), INa.L inhibitors, decreased INa.L in cardiomyocytes in the presence of 300 μM H2O2. H2O2 (300 μM) increased the reverse INCX and this increase was significantly attenuated by either 20 μM resveratrol or 4 μM ranolazine or 4 μM TTX. In addition, 10 μM resveratrol and 2 μM TTX significantly depressed the increase by 150 μM H2O2 of the diastolic intracellular Ca2+ fura-2 fluorescence intensity (FFI), fura-fluorescence intensity change (△FFI), maximal velocity of intracellular Ca2+ transient rise and decay. As expected, 2 μM TTX had no effect on ICa.L. Conclusion: Resveratrol protects the cardiomyocytes by inhibiting the H2O2-induced augmentation of INa.L.and may contribute to the reduction of ischemia-induced lethal arrhythmias. © 2012 Qian et al.