Voltage- and use-dependent effect of 7-chlor-benzyltetrahydropalmatine on sodium currents in guinea pig ventricular myocytes
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The whole-cell patch-clamp technique was employed to obtain information about the voltage-dependence and kinetics of interaction of 7-chlor-benzyltetrahydropalmatine (7-C1-BTHP) with cardiac sodium channels. 7-C1-BTHP (30 mol/L) significantly decreased the peak sodium current (from 7. 8±1. 8 nA to 5. 3±1. 4 nA,P<0. 01,n = 5), without producing a shift of the current-voltage curve. It shifted the inactivation curves of sodium current to hyperpolarized potentials, and the V0.5 was shifted from - (82. 5±2. 5) mV to - (95±2. 4) mV (P <0. 05,n = 4). 7-C1-BTHP produced a significant use-dependent effect that was proportional to the duration of the voltage step. In addition, 7-C1-BTHP slowed the recovery of sodium channel from inactivation, which could explain its use-dependent effects on sodium current. The characteristics of 7-C1-BTHP blockage suggest that this agent binds preferentially to inactivated sodium channels.
Key words7-chlor-benzyltetrahydropalmatine myocardium sodium channel current guinea pig ventricular myocytes
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