Effect of resveratrol on L-type calcium current in rat ventricular myocytes.
OBJECTIVE
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 micromol/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 micromol/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 micromol/L) shifted the steady-state activation curve of I(Ca-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 micromol/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 (Na(3)VO(4); 1 mmol/L), a potent inhibitor of tyrosine phosphatase, significantly inhibited the effects of resveratrol (P<0.01).


CONCLUSIONS
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.
Zhang
Li-ping
LP
Department of Physiology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, China.
Yin
Jing-xiang
JX
Liu
Zheng
Z
Zhang
Yi
Y
Wang
Qing-shan
QS
Zhao
Juan
J
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006352:Heart Ventricles; D008297:Male; D032383:Myocytes, Cardiac / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage / Q000494:pharmacology*; D014638:Vanadates / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D020746:Calcium Channels, L-Type; D013267:Stilbenes; D014638:Vanadates; D011505:Protein-Tyrosine Kinases; D000077185:Resveratrol