Morad M, Goldman Y E, Trentham D R
Nature. 1983;304(5927):635-8. doi: 10.1038/304635a0.
'Calcium-antagonists' are a group of pharmacological agents which are potent vasodilators and are clinically used for the treatment of angina. They are thought to block Ca2+ channels in vascular smooth muscle and myocardium but other sites of action have been proposed. These agents bind tightly to heart muscle and suppress action potential and contraction. Nifedipine and nisoldipine (BAY K 5552) are Ca2+ antagonists which have o-nitrobenzyl groups and are photolabile. We have found that short pulses of UV light rapidly inactivate these drugs in ventricular muscle. This observation allowed us to study the effect of Ca2+ antagonists on action potential, Ca2+ current and tension in conditions in which diffusion of those drugs from their site of action was not rate limiting. Our studies, described here, suggest that the primary mechanism of action of Ca2+ antagonists is the blockade of the Ca2+ channel and support the idea that extracellular space is the immediate source of contractile Ca2+ in the frog heart.
“钙拮抗剂”是一类药理制剂，它们是强效血管扩张剂，临床上用于治疗心绞痛。人们认为它们能阻断血管平滑肌和心肌中的Ca2+通道，但也有人提出了其他作用位点。这些制剂与心肌紧密结合，抑制动作电位和收缩。硝苯地平和尼索地平（BAY K 5552）是具有邻硝基苄基且对光不稳定的钙拮抗剂。我们发现，短脉冲紫外光可使心室肌中的这些药物迅速失活。这一观察结果使我们能够在这些药物从作用位点扩散不是限速因素的条件下，研究钙拮抗剂对动作电位、Ca2+电流和张力的影响。我们在此描述的研究表明，钙拮抗剂的主要作用机制是阻断Ca2+通道，并支持细胞外空间是蛙心收缩性Ca2+直接来源的观点。
