汉防已甲素对心肌细胞电生理和心肌肌浆网钙吸收的效应

摘要

Objective To study the effects of tetrandrine, a Chinese herbal medicine, on the action potential (AP),rncontraction as well as sarcoplasmic reticulum (SR) calcium uptake of myocardium in guinea-pigs and dogs.rnMethods Changes in AP, dV/dt, peak tension (PT) and dT/dt of myocardial cells were studied using the rntechnique of glass electrode. Changes of the calcium uptake rate by sarcoplasmic reticulum and release of rninorganic phosphate from sarcoplasmic reticulum were assessed with biochemical techniques.rnResults Tetrandrine exerts a concentration-dependent and frequency-dependent negative inotropic effect rnand shortens action potential duration. Tetrandrine depresses both dT(E)/dt and dT(L)/dt as well as the rntension of myocardium, and reduces dV/dt and amplitude only in the slow action potential, thus implying rnthat tetrandrine blocks the slow calcium channel. In addition, compared with thapsigargin, a specific rninhibitor of Ca2+-ATPase on SR, tetrandrine more apparently suppresses the contraction of the rnmyocardium.rnConclusions Tetrandrine is a wide-range calcium antagonist of plant origin. Not only it blocks the voltagernoperated calcium channels as other authors reported, but also may play an important role in affecting the rnfunction of Ca2+ -ATPase and calcium release channels on SR. From this study, we also suggest that the rncalcium channel appears to be more critical than SR for the contraction of my ocardium.%目的本文旨在研究汉防已甲素对豚鼠及狗的心肌动作电位(AP)、收缩力及肌浆网钙吸收的作用。rn方法用玻璃微电极的方法，研究用药后心肌细胞AP、dV/dt、峰张力(PT)及dT/dt等指标的改变，并用生rn化方法估价用药后心肌肌浆网钙吸收率及无机磷释放等指标的变化。rn结果汉防已甲素起着浓度依赖性和频率依赖性负性变力性作用，且缩短了动作电位时程。汉防已甲素rn抑制心肌dT(E)/dt和dT(L)/dt，也抑制了心肌张力，并降低了慢动作电位的dV/dt和幅度，这些暗示汉防rn已甲素可阻止慢钙通道。另外，与Thapsigargin(一种特异性肌浆网Ca2+-ATP酶抑制剂)进行了比较，汉防rn已甲素较之更为明显地抑制了心肌的收缩。rn结论汉防已甲素是一种植物性广谱钙离子拮抗剂。它不仅阻止电压操纵的钙通道(象其它作者所报导rn的那样)，而且在影响Ca2+-ATP酶及肌浆网钙释放通道方面也起着重要的作用。我们的资料提示钙通道rn对心肌收缩似乎比肌浆网更为关键。