The ionic mechanism of tetrandrine, an alkaloid extracted from the Chinese medicinal herb Radix stephania tetrandrae, was investigated in A7r5 vascular smooth muscle cells. The nystatin-perforated whole-cell voltage-clamp technique was performed to examine the effects of tetrandrine on ionic currents. Tetrandrine (1-100 μM) reversibly caused an inhibition of L-type voltage-dependent Ca2+ current (I(Ca,L)) in a concentration-dependent manner. Tetrandrine did not cause any change in the overall shape of the current-voltage relationship of I(Ca,L). The IC50 value of tetrandrine-induced inhibition of I(Ca,L) was 5 μM. In the presence of Bay K 8644 (3 μM) or cyclopiazonic acid (30 μM), tetrandrine still produced a significant inhibition of I(Ca,L). The inhibitory effects of tetrandrine on I(Ca,L) exhibited tonic and use-dependent characteristics. Moreover. tetrandrine (3 μM) Shifted the steady-state inactivation curve of I(Ca,L) to more negative membrane potentials by approximately - 15 mV. These results indicate that tetrandrine directly inhibits the voltage-dependent L-type Ca2+ current in vascular smooth muscle cells, which may predominantly contribute to the vasodilatory actions of tetrandrine.
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