Howlett S E, Gordon T
Department of Pharmacology, University of Alberta, Edmonton, Canada.
J Mol Cell Cardiol. 1990 Sep;22(9):975-85. doi: 10.1016/0022-2828(90)91037-8.
The characteristics of high affinity dihydropyridine binding sites were compared in normal and cardiomyopathic hamster hearts to probe for possible defects in the calcium channel which could lead to calcium overload and, in turn, to the muscle necrosis characteristic of cardiomyopathy. Kinetic studies of the temperature dependence of [3H]-nitrendipine binding to ventricular homogenates from 60-day-old normal and cardiomyopathic hamsters showed that, in normal hamsters, the rate of dissociation (0.049 +/- 0.006/min at 25 degrees C) was highly temperature-dependent (Q10 = 4.40 +/- 0.69) and that neither the rate nor the temperature dependence was influenced by disease. The rate of association (1.12 +/- 0.11/min/nM at 25 degrees C) was weakly temperature-dependent (Q10 = 1.25 +/- 0.04) and similarly unaffected by disease. The rate of dissociation of [3H]-nitrendipine was increased by verapamil and decreased by diltiazem with little effect on the association rate. Allosteric interactions of diltiazem and verapamil with the dihydropyridine receptor were identical in normal and cardiomyopathic hearts and, together with the normal temperature sensitivity, show that there is no abnormality at the related binding sites for nitrendipine, verapamil and diltiazem in the calcium channel of the cardiomyopathic heart.
比较正常和心肌病仓鼠心脏中高亲和力二氢吡啶结合位点的特征，以探究钙通道可能存在的缺陷，这些缺陷可能导致钙超载，进而导致心肌病特有的肌肉坏死。对[3H] - 尼群地平与60日龄正常和心肌病仓鼠心室匀浆结合的温度依赖性进行动力学研究表明，在正常仓鼠中，解离速率（25℃时为0.049±0.006/分钟）高度依赖温度（Q10 = 4.40±0.69），且速率和温度依赖性均不受疾病影响。结合速率（25℃时为1.12±0.11/分钟/纳摩尔）对温度的依赖性较弱（Q10 = 1.25±0.04），同样不受疾病影响。维拉帕米可增加[3H] - 尼群地平的解离速率，地尔硫卓则降低其解离速率，而对结合速率影响较小。地尔硫卓和维拉帕米与二氢吡啶受体的变构相互作用在正常和心肌病心脏中是相同的，并且与正常的温度敏感性一起表明，心肌病心脏钙通道中尼群地平、维拉帕米和地尔硫卓的相关结合位点没有异常。
