Boyden Penelope A, ter Keurs Henk
Department of Pharmacology, Center for Molecular Therapeutics, Columbia University, NY 10032, USA.
Pharmacol Ther. 2005 Nov;108(2):149-79. doi: 10.1016/j.pharmthera.2005.03.011. Epub 2005 Jul 20.
Under several types of conditions, reversal of steps of excitation-contraction coupling (RECC) can give rise to nondriven electrical activity. In this review we explore those conditions for several cardiac cell types (SA, atrial, Purkinje, ventricular cells). We find that abnormal spontaneous Ca2+ release from intracellular Ca2+ stores, aberrant Ca2+ influx from sarcolemmal channels or abnormal Ca2+ surges in nonuniform muscle can be the initiators of the RECC. Often, with such increases in Ca2+, spontaneous Ca2+ waves occur and lead to membrane depolarizations. Because the change in membrane voltage is produced by Ca2+-dependent changes in ion channel function, we also review here what is known about the molecular interaction of Ca2+ and several Ca2+-dependent processes, including the intracellular Ca2+ release channels implicated in the genetic basis of some forms of human arrhythmias. Finally, we review what is known about the effectiveness of several agents in modifying such Ca2+-dependent arrhythmias.
在几种类型的条件下，兴奋 - 收缩偶联步骤的逆转（RECC）可引发非驱动性电活动。在本综述中，我们探讨了几种心脏细胞类型（窦房结细胞、心房细胞、浦肯野细胞、心室细胞）的这些条件。我们发现，细胞内钙库中异常的自发钙释放、肌膜通道异常的钙内流或不均匀肌肉中异常的钙激增可能是RECC的起始因素。通常，随着钙的这种增加，自发钙波会出现并导致膜去极化。由于膜电压的变化是由离子通道功能中钙依赖性变化产生的，我们在此还回顾了关于钙与几种钙依赖性过程的分子相互作用的已知信息，包括与某些形式的人类心律失常遗传基础相关的细胞内钙释放通道。最后，我们回顾了关于几种药物在改变此类钙依赖性心律失常方面有效性的已知信息。
