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, on the action po tential (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 cells were studi ed using the technique of glass electrode. Changes of the calcium uptake rate b y sarcoplasmic reticulum and release of inorganic phosphate from sarcoplasmic re ticulum were assessed with biochemical techniques.Results Tetrandrine exerts a concentration-dependent and frequency-dependent negative inotropic effect and shortens action potential duration. Tetrandrine depresses bothdT(E)/dt and dT(L)/dt as well as the tension of myocardium, and reduces d V/dt and amplitude only in the slow action potential, thus implying that tetrand rine blocks the slow calcium channel. In addition, compared with thapsigargin, a specific inhibitor of Ca(2+)-ATPase on SR, tetrandrine more apparently su ppresses the contraction of the myocardium.Conclusions Tetrandrine is a wide-range calcium antagonist of plant origin. Not only it bl ocks the voltage-operated calcium channels as other authors reported, but a lso may play an important role in affecting the function of Ca(2+)-ATPase a nd calcium release channels on SR. From this study, we also suggest that the ca lcium channel appears to be more critical than SR for the contraction of myocard ium.