Effect of resveratrol on L-type calcium current in rat ventricular myocytes
Abstract
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 μmol/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 μmol/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 μmol/L) shifted the steady-state activation curve of ICa-L to the
right and changed the half-activation potential (V0.5) 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 ICa-L, but did markedly shift the timedependent
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 ICa-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:
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 μmol/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 μmol/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 μmol/L) shifted the steady-state activation curve of ICa-L to the
right and changed the half-activation potential (V0.5) 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 ICa-L, but did markedly shift the timedependent
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 ICa-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.