Effect of resveratrol on L-type calcium current in rat ventricular myocytes

Aim: To study the effect of resveratrol on L-type calcium current (ICa-L) in isolated rat ventricular myocytes and the mechanisms underlying these effects. Methods:ICa-L was examined in isolated single rat ventricular myocytes by using the whole cell patch-clamp recording technique. Results: Resveratrol (10-40 mu mol/L) reduced the peak amplitude of ICa-L and shifted the current-voltage (I-V) curve upwards in a concentration-dependent manner. Resveratrol (10, 20, 40 mu mol/L) decreased the peak amplitude of ICa-L from -14.2 +/- 1.5 pA/pF to -10.5 +/- 1.5 pA/pF (P < 0.05), -7.5 +/- 2.4 pA/pF (P < 0.01), and -5.2 +/- 1.2 pA/pF (P < 0.01), respectively. Resveratrol (40 mu mol/L) shifted the steady-state activation curve of ICa-L to the right and changed the half-activation potential (V-0.5) from -19.4 +/- 0.4 mV to -15.4 +/- 1.9 mV (P < 0.05). Resveratrol at a concentration of 40 mu mol/L did not affect the steady-state inactivation curve of ICa-L, but did markedly shift the time-dependent recovery curve of ICa-L to the right, and slow down the recovery of ICa-L from inactivation. Sodium orthovanadate (Na3VO4; 1 mmol/L), a potent inhibitor of tyrosine phosphatase, significantly inhibited the effects of resveratrol (P < 0.01). Conclusion: Resveratrol inhibited I-Ca-L mainly by inhibiting the activation of L-type calcium channels and slowing down the recovery of L-type calcium channels from inactivation. This inhibitory effect of resveratrol was mediated by the inhibition of protein tyrosine kinase in rat ventricular myocytes.