Effects of ellagic acid on contractility and ca currents in rat cardiomyocytes

Recent evidences have shown that phenolic structures exert many biological functions. Ellagic acid (EA), a phenolic compound, has been suggested to have cardioprotective effects. In this study we aimed to investigate the effect of EA on cardiac Ca2+ currents and contractility in rat ventricular myocytes and to elucidate the underlying mechanisms of these changes. All records measured from the freshly isolated ventricular myocytes of rat heart. We found that EA dose dependently reduced Ca2+ currents with EC50=23 nM. EA decreased voltage dependent L-type Ca2+ current density (ICaL) but it didn?t affect the inactivation and reactivation parameters. Inhibition of adenylate cyclase (AC) with SQ 22536(10 µM) and using antioxidant (probucol) had no effect on EA modulation of ICaL. Interestingly, blockage of nitric oxide synthase (NOS) with L-NAME and guanylate cyclase (GC) with ODQ (1 µM) abolished inhibitory effect of EA on ICaL. Moreover, EA dose dependently blunted fractional shorthening of ventricular myocytes. Besides, EA application revealed a significant prolongation in action potential duration (APD) in ventricular myocytes. In conclusion, EA affects ionic and mechanical properties of ventricular myocytes even at nanomolar concentrations. It reduces ICaL and fractional shorthening and prolongs APD significantly. These findings indicated that EA supresses ICaL and exerts negative inotropic effects through activation of NOS-GC-cGMP pathway. On the other hand, AP prolongation implies that EA might also have effect on potassium currents. Key Words: Ellagic Acid, Ca2+ Currents, Fractional Shorthening, Action Potential.