ionic mechanisms of tetradrine in cultured rat aortic smooth muscle cells

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.