Katz A M
J Clin Hypertens. 1986 Sep;2(3 Suppl):28S-37S.
The calcium-channel blockers represent a group of organic chemical structures that share the ability to inhibit Ca2+ entry into excitable cells. In coronary and peripheral arterial smooth muscle and the heart, inhibition of Ca2+ entry blunts the ability of Ca2+ to serve as an intracellular messenger. Thus, calcium-channel blockers are smooth-muscle dilators and have a negative inotropic effect on the working myocardial cells of the atria and ventricles. Calcium-channel blockers also have effects on impulse formation and conduction in some regions of the heart. A fast, Na+-dependent ionic current is responsible for the upstroke of the action potential in the working cells of the atria and ventricles and in the rapidly conducting cells of the His-Purkinje system, so that the calcium-channel blockers do not inhibit conduction in these cells. In the sinoatrial and atrioventricular nodes, where depolarization is due primarily to a Ca2+-dependent slow inward current, the calcium-channel blockers slow the sinus pacemaker and inhibit atrioventricular conduction. The actions of different calcium-channel blockers are not always similar; for example, nifedipine is much more potent as an inhibitor of calcium channels in smooth muscle than in the heart, whereas verapamil and diltiazem are approximately equipotent in heart and vascular smooth muscle. It is likely that the calcium-channel blockers reach their specific binding sites in membranes by first dissolving in the phospholipid bilayer, after which they may interact with hydrophobic regions of proteins that make up, or regulate, these channels. Further knowledge of these molecular properties should facilitate the development of new calcium-channel blockers with improved specificity.
钙通道阻滞剂是一类具有共同特性的有机化学结构，即能够抑制钙离子进入可兴奋细胞。在冠状动脉和外周动脉平滑肌以及心脏中，抑制钙离子进入会削弱钙离子作为细胞内信使的能力。因此，钙通道阻滞剂是平滑肌舒张剂，对心房和心室的工作心肌细胞具有负性肌力作用。钙通道阻滞剂对心脏某些区域的冲动形成和传导也有影响。快速的、依赖钠离子的离子电流负责心房和心室工作细胞以及希氏 - 浦肯野系统快速传导细胞动作电位的上升支，所以钙通道阻滞剂不会抑制这些细胞的传导。在窦房结和房室结，去极化主要归因于依赖钙离子的缓慢内向电流，钙通道阻滞剂会减慢窦性起搏并抑制房室传导。不同钙通道阻滞剂的作用并不总是相似的；例如，硝苯地平作为平滑肌中钙通道的抑制剂比在心脏中更有效，而维拉帕米和地尔硫䓬在心脏和血管平滑肌中的作用大致相当。钙通道阻滞剂可能首先溶解在磷脂双分子层中，然后到达膜中的特定结合位点，之后它们可能与构成或调节这些通道的蛋白质的疏水区域相互作用。对这些分子特性的进一步了解应有助于开发具有更高特异性的新型钙通道阻滞剂。
