Acta Pharmacologica Sinica 2006 February; 27 (2): 179-183; doi: 10.1111/j.1745-7254.2006.00250.x

Aim: To study the effect of resveratrol on L-type calcium current (I_Ca-L) in isolated rat ventricular myocytes and the mechanisms underlying these effects.

Methods: I_Ca-L was examined in isolated single rat ventricular myocytes by using the whole cell patch-clamp recording technique.

Results: Resveratrol (10-40 µmol/L) reduced the peak amplitude of I_Ca-L and shifted the current-voltage (I-V) curve upwards in a concentration-dependent manner. Resveratrol (10, 20, 40 µmol/L) decreased the peak amplitude of I_Ca-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 µmol/L) shifted the steady-state activation curve of I_Ca-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 µmol/L did not affect the steady-state inactivation curve of I_Ca-L, but did markedly shift the time-dependent recovery curve of I_Ca-L to the right, and slow down the recovery of I_Ca-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.

Keywords: resveratrol; patch-clamp techniques; myo-cardium; L-type calcium channels