Resveratrol Attenuates The Na⁺-dependent Ca²⁺ Overload Induced By H₂O₂-increasedl Late Sodium Current In Ventricular Myocytes

Background/Aims: Resveratrol has been demonstrated to be protective in the cardiovascularsystem. 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 ventricularmyocytes.Methods: INa.L, INCX,L-type Ca²⁺current （ICa.L） and intracellular Ca²⁺properties were determinedusing whole-cell patch-clamp techniques and dual-excitation fluorescence photomultipliersystem （IonOptix）, respectively,f in rabbit ventricular myocytes.Results: Resveratrol （10,20,40and80μM） decreased INa.Lin myocytes both in the absence andpresence of H₂O₂（300μM） in a concentration dependent manner. Ranolazine （3-9μM） andtetrodotoxin （TTX,4μM）, INa.Linhibitors, decreased INa.Lin cardiomyocytes in the presence of300μM H₂O₂. H₂O₂（300μM） increased the reverse INCXand this increase was significantlyattenuated by either20μM resveratrol or4μM ranolazine or4μM TTX. In addition,10μMresveratrol and2μM TTX significantly depressed the increase by150μM H₂O₂of the diastolicintracellular Ca²⁺fura-2fluorescence intensity （FFI）, fura-fluorescence intensity change （△FFI）,maximal velocity of intracellular Ca²⁺transient rise and decay. As expected,2μM TTX had noeffect on ICa.L.Conclusion: Resveratrol protects the cardiomyocytes by inhibiting the H₂O₂-inducedaugmentation of INa.L.and may contribute to the reduction of ischemia-induced lethalarrhythmias. Background/Aims: Resveratrol has been demonstrated to be protective in the cardiovascularsystem. 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 ventricularmyocytes.Methods: INa.L, INCX,L-type Ca²⁺current （ICa.L） and intracellular Ca²⁺properties were determinedusing whole-cell patch-clamp techniques and dual-excitation fluorescence photomultipliersystem （IonOptix）, respectively, in rabbit ventricular myocytes.Results: Resveratrol （10,20,40and80μM） decreased INa.Lin myocytes both in the absence andpresence of H2O2（300μM） in a concentration dependent manner. Ranolazine （3-9μM） andtetrodotoxin （TTX,4μM）, INa.Linhibitors, decreased INa.Lin cardiomyocytes in the presence of300μM H2O2. H2O2（300μM） increased the reverse INCXand this increase was significantlyattenuated by either20μM resveratrol or4μM ranolazine or4μM TTX. In addition,10μMresveratrol and2μM TTX significantly depressed the increase by150μM H2O2of the diastolicintracellular Ca²⁺fura-2fluorescence intensity （FFI）, fura-fluorescence intensity change （△FFI）,maximal velocity of intracellular Ca²⁺transient rise and decay. As expected,2μM TTX had noeffect on ICa.L.Conclusion: Resveratrol protects the cardiomyocytes by inhibiting the H2O2-inducedaugmentation of INa.L.and may contribute to the reduction of ischemia-induced lethalarrhythmias.