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 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 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.
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Zhang, Lp., Yin, Jx., Liu, Z. et al. Effect of resveratrol on L-type calcium current in rat ventricular myocytes. Acta Pharmacol Sin 27, 179–183 (2006). https://doi.org/10.1111/j.1745-7254.2006.00250.x
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DOI: https://doi.org/10.1111/j.1745-7254.2006.00250.x
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