Frequency-dependent depression of Vmax in K(+)-depolarized guinea pig papillary muscle by tetrandrine

Abstract

The effect of tetrandrine (Tet), a calcium antagonist, on the maximal upstroke velocity (Vmax) of depolarization in K(+)-depolarized guinea pig papillary muscles was studied by standard microelectrode method with computer. The results showed that: (1) the resting block of Tet on Vmax was concentration dependent; (2) the drug (50 or 100 mumol.L-1) caused a marked frequency-dependent block of Vmax, which accounted for 65 +/- 8% of total block at a concentration of 100 mumol.L-1 and the pacing frequency of 0.3 Hz; (3) the recovery kinetics of Vmax could be characterized as a biexponential function, of which the second phase was prolonged by the drug; (4) compared with verapamil, nitrendipine, and diltiazem, the above-mentioned effects of Tet on Vmax were similar to those of diltiazem. These results suggest that Tet can block calcium channel in both frequency-dependent and frequency-independent manner, mainly the former.