Chachin Motohiko, Kurachi Yoshihisa
Department of Pharmacology II, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
Nihon Yakurigaku Zasshi. 2002 Jun;119(6):345-51. doi: 10.1254/fpj.119.345.
Recently, there has been considerable attention focused on drugs that prolong the QT interval of the electrocardiogram. This occasionally evolves to fetal, polymorphic ventricular arrhythmias, torsades de pointes. Therefore, the early detection of the risk of drug-induced QT prolongation is important for avoiding the adverse cardiovascular effect in clinical use. It has been suggested that the QT prolongation and ventricular arrhythmia caused by drugs might be secondary to their ability to interfere with cardiac potassium channels involved in action potential repolarization and in particular with rapidly activating delayed rectifier K+ current (IKr). In cardiac myocytes, IKr contributes to termination of the plateau phase of action potential. The ether-a-go-go related gene in humans expressed a K+ channel current with biophysical characteristics similar to those of IKr. Electrophysiological studies on cloned HERG channels can provide fundamental information concerning the cardiac safety profile of new developing drugs.
最近，延长心电图QT间期的药物受到了广泛关注。这偶尔会演变为胎儿多形性室性心律失常——尖端扭转型室速。因此，早期检测药物诱导的QT延长风险对于避免临床使用中的不良心血管效应很重要。有人提出，药物引起的QT延长和室性心律失常可能继发于它们干扰参与动作电位复极化的心脏钾通道的能力，特别是快速激活延迟整流钾电流（IKr）。在心肌细胞中，IKr有助于动作电位平台期的终止。人类的醚 - 去极化相关基因表达了一种具有与IKr相似生物物理特性的钾通道电流。对克隆的HERG通道进行电生理研究可以为新研发药物的心脏安全性提供基本信息。
