Effect of tetrandrine on cellular electrophysiology and calcium uptake of myocardium in guinea pigs and dogs

Objective To study the effects of tetrandrine, a Chinese herbal medicine, o n the action potential (AP), contraction as well as sarcoplasmic reticulum (SR) calcium uptake of myocardium in guinea-pigs and dogs. Methods Changes in AP, dV/dt, peak tension (PT) and dT/dt of myocardial cel ls were studied using the technique of glass electrode. Changes of the calc ium uptake rate by sarcoplasmic reticulum and release of inorganic phosphat e from sarcoplasmic reticulum were assessed with biochemical techniques. Results Tetrandrine exerts a concentration-dependent and frequency-dependen t negative inotropic effect and shortens action potential duration. Tetrand rine depresses both dT(E)/dt and dT(L)/dt as well as the tension of myocard ium, and reduces dV/dt and amplitude only in the slow action potential, thu s implying that tetrandrine blocks the slow calcium channel. In addition, c ompared with thapsigargin, a specific inhibitor of Ca2+-ATPase on SR, tetra ndrine more apparently suppresses the contraction of the myocardium. Conclusions Tetrandrine is a wide-range calcium antagonist of plant origin. Not only it blocks the voltage-operated calcium channels as other authors reported, but also may play an important role in affecting the function of Ca2+-ATPase and calcium release channels on SR. From this study, we also su ggest that the calcium channel appears to be more critical than SR for the contraction of myocardium.