Effects of Tetrandrine on Ca2+- and Na+-Currents of Single Bullfrog Cardiomyocytes

Tetrandrine is a natural alkaloid classified as a calcium antagonist. However, its precise actions on Ca2+-currents in cardiac cells have not been fully characterized. In the present study, we have investigated the mechanism of action of tetrandrine on the Ca2+-currents of single bullfrog cardiac cells, using the patch-clamp technique. Tetrandrine slightly increased ICaL from negative holding potentials (-100 mV) at low concentrations (10 nM-1 μM) and inhibited it at higher concentrations. At depolarized holding potentials (-50 mV) only an enhanced inhibition was seen. Tetrandrine blockade of the L-type Ca2+-current (ICaL) was mostly tonic. This is similar to ICaL blockade by nifedipine but not by verapamil, the latter being mostly use-dependent. Use-dependent effects of tetrandrine and nifedipine were evident at high rates. Availability curves were shifted leftwards (10-12 mV) by tetrandrine (10 μM) and nifedipine (1 μM). The T-type Ca2+-current (ICaT), although less sensitive, was decreased by both agents in a voltage-independent way. Tetrandrine (10-30 μM) but not nifedipine (1-10 μM), depressed the Na+-current (INa) in tonic, use- and voltage-dependent manners. We conclude that tetrandrine and nifedipine share some common actions on cardiac Ca2+-channels, while showing differences in their actions on Na+-channels. The depression of INa by tetrandrine suggests it could be effective on supraventricular tachycardias.