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

来源 :Acta Pharmacologica Sinica | 被引量 : 0次 | 上传用户:q5108947
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Aim:To study the effect of resveratrol on L-type calcium current(I_(Ca-L))in isolatedrat ventricular myocytes and the mechanisms underlying these effects.Methods:I_(Ca-L) was examined in isolated single rat ventricular myocytes by using the wholecell patch-clamp recording technique.Results:Resveratrol(10-40 μmol/L)re-duced the peak amplitude of I_(Ca-L) and shifted the current-voltage(I-V)curveupwards 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 theright 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 notaffect 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 ofI_(Ca-L) from inactivation.Sodium orthovanadate(Na_3VO_4;1 mmol/L),a potentinhibitor of tyrosine phosphatase,significantly inhibited the effects of resveratrol(P<0.01).Conclusion:Resveratrol inhibited I_(Ca-L) mainly by inhibiting the activa-tion of L-type calcium channels and slowing down the recovery of L-type cal-cium channels from inactivation.This inhibitory effect of resveratrol was medi-ated by the inhibition of protein tyrosine kinase in rat ventricular myocytes. Aim: To study the effect of resveratrol on L-type calcium current (I_ (Ca-L)) in isolatedrat ventricular myocytes and the mechanisms underlying these effects. Methods: I_ (Ca-L) was examined in isolated single rat ventricular myocytes by using the wholecell patch-clamp recording technique. Results: Resveratrol (10-40 μmol / L) re-duced the peak amplitude of I_ (Ca-L) and shifted the current- voltage (IV) curveupwards in a concentration-dependent manner. 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 / pA (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, an Inhibition of I_ (Ca-L) from inactivation. Sodium orthovanadate (Na_3VO_4; 1 mmol / L), a potent inhibitor of tyrosine phosphatase, significantly inhibited the effects of resveratrol (P <0.01) -L) mainly by inhibiting the activa-tion of L-type calcium channels and slowing down the recovery of L-type cal-cium channels from inactivation. This inhibitory effect of resveratrol was medi- ated by the inhibition of protein tyrosine kinase in rat ventricular myocytes.
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