Add time:08/12/2019         Source:sciencedirect.com

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 (ICa,L) in a concentration-dependent manner. Tetrandrine did not cause any change in the overall shape of the current–voltage relationship of ICa,L. The IC50 value of tetrandrine-induced inhibition of ICa,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 ICa,L. The inhibitory effects of tetrandrine on ICa,L exhibited tonic and use-dependent characteristics. Moreover. tetrandrine (3 μM) shifted the steady-state inactivation curve of ICa,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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