Resveratrol Attenuates The Na+-Dependent Intracellular Ca2+ Overload By Inhibiting H2o2-Induced Increase In Late Sodium Current In Ventricular Myocytes

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 (I-Na.L) which augmented the reverse Na+-Ca2+ exchanger current (I-NCX), and the diastolic intracellular Ca2+ concentration in ventricular myocytes.Methods: I-Na.L, I-NCX, L-type Ca2+ current (I-Ca.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 mu M)decreased I-Na.L in myocytes both in the absence and presence of H2O2 (300 mu M) in a concentration dependent manner. Ranolazine (3-9 mu M) and tetrodotoxin (TTX, 4 mu M), I-Na.L inhibitors, decreased I-Na.L in cardiomyocytes in the presence of 300 mu M H2O2. H2O2 (300 mu M) increased the reverse I-NCX and this increase was significantly attenuated by either 20 mu M resveratrol or 4 mu M ranolazine or 4 mu M TTX. In addition, 10 mu M resveratrol and 2 mu M TTX significantly depressed the increase by 150 mu M H2O2 of the diastolic intracellular Ca2+ fura-2 fluorescence intensity (FFI), fura-fluorescence intensity change (Delta FFI), maximal velocity of intracellular Ca2+ transient rise and decay. As expected, 2 mu M TTX had no effect on I-Ca.L.Conclusion: Resveratrol protects the cardiomyocytes by inhibiting the H2O2-induced augmentation of I-Na.L and may contribute to the reduction of ischemia-induced lethal arrhythmias. Citation: Qian C, Ma J, Zhang P, Luo A, Wang C, et al. (2012) Resveratrol Attenuates the Na+-Dependent Intracellular Ca2+ Overload by Inhibiting H2O2-Induced Increase in Late Sodium Current in Ventricular Myocytes. PLoS ONE 7(12): e51358. doi:10.1371/journal.pone.0051358