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Effect of genistein on L-type calcium current in guinea pig ventricular myocytes.

This paper was aimed to study the effect of genistein (GST) on L-type calcium current (I(Ca,L)) in isolated guinea pig ventricular myocytes using whole cell patch-clamp recording technique. The results are as follows. (1) GST (10, 50, 100 micromol/L) reduced the voltage-activated peak amplitude of I(Ca,L) in a concentration-dependent manner. Daidzein (100 micromol/L), a structural analogue of GST which has little or no inhibitory effect on tyrosine kinase, produced no effect over the same concentration range on I(Ca,L) (n=5, P>0.05). (2) GST up- shifted the current-voltage (I-V) curve, but the characteristics of I-V relationship were not significantly altered, and the maximal activation voltage of I(Ca,L) was not different from that of control. GST did not affect the activation kinetics of I(Ca,L). (3) GST markedly shifted the steady-state inactivation curve of I(Ca,L) to the left, and accelerated the voltage-dependent steady-state inactivation of I(Ca,L). V(0.5) value was -28.6 +/-0.6 mV in the control and -32.8 +/-1.1 mV in the presence of GST. The kappa values were 5.8 +/-0.5 mV and 6.5 +/-0.9 mV, respectively (n=6, P<0.05). (4) GST markedly shifted the curve of time-dependent recovery of I(Ca,L) from the steady-state inactivation to the right, and slowed down the recovery of I(Ca,L) from inactivation (n=7, P<0.01). (5) Sodium orthovanadate (1 mmol/L), a potent inhibitor of tyrosine phosphatase, significantly inhibited GST-induced inhibition (n=6, P<0.01). From the results obtained it is concluded that genistein inhibits I(Ca,L) and acts on the inactivated state of L-type calcium channel. This inhibitory effect of GST involves protein tyrosine kinase inhibition in guinea pig ventricular myocytes.