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 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 cells were studied using the technique of glass electrode. Changes of the calcium uptake rate by sarcoplasmic reticulum and release of inorganic phosphate from sarcoplasmic reticulum were assessed with biochemical techniques.


RESULTS
Tetrandrine exerts a concentration-dependent and frequency-dependent negative inotropic effect and shortens action potential duration. Tetrandrine depresses both dT(E)/dt and dT(L)/dt as well as the tension of myocardium, and reduces dV/dt and amplitude only in the slow action potential, thus implying that tetrandrine blocks the slow calcium channel. In addition, compared with thapsigargin, a specific inhibitor of Ca(2+)-ATPase on SR, tetrandrine 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 Ca(2+)-ATPase and calcium release channels on SR. From this study, we also suggest that the calcium channel appears to be more critical than SR for the contraction of myocardium.
Guan
S
S
Department of Geriatric Medicine, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China.
Lynch
C
C
D000200:Action Potentials / Q000187:drug effects; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D044182:Benzylisoquinolines / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D003331:Coronary Vessels / Q000378:metabolism*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology
D000470:Alkaloids; D044182:Benzylisoquinolines; D010710:Phosphates; C009438:tetrandrine; D019284:Thapsigargin; D002118:Calcium