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

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Author:
No author available
Journal Title:
ACTA PHYSIOLOGICA SINICA
Issue:
4
DOI:
10.3321/j.issn:0371-0874.2004.04.007
Key Word:
三羟异黄酮;膜片箝技术;心肌;L-型钙通道;genistein;patch-clamp techniques;myocardium;L-type calcium channels

Abstract: This paper was aimed to study the effect of genistein (GST) on L-type calcium current (ICa,L)in isolated guinea pig ventricular myocytes using whole cell patch-clamp recording technique. The results are as follows. (1) GST (10, 50, 100 μmol/L) reduced the voltageactivated peak amplitude of ICa,L in a concentration-dependent manner. Daidzein (100 μrnol/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 ICa,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 ICa, L was not different from that of control. GST did not affect the activation kinetics of ICa, L. (3) GST markedly shifted the steady-state inactivation curve of ICa,L to the left, and accelerated the voltage-dependent steady-state inactivation of ICa,L. V0.5 value was -28.6 ± 0.6 mV in the control and -32.8 ± 1.1 mV in the presence of GST. The κ 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 Ica,L from the steady-state inactivation to the right, and slowed down the recovery of ICa,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 ICa,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.

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