抗心律失常药物作用的靶点——HERG K^+通道

HERG K^+ channel,the target of anti-arrhythmias drugs

快速延迟整流钾电流(rapidly activating com ponent of delayed rectifier potassium current,IKr)在心肌动作电位复极化过程中发挥重要作用。HERG基因编码心脏快速延迟整流钾通道的α亚基,HERG基因突变导致遗传性长QT间期综合征(long QT syndrome,LQTS),另外IKr/HERG通道是绝大多数能引起心脏QT间期延长药物的作用靶标,其他一些化学结构不同的药物也可阻断该通道,引起QT间期延长,甚至发展成获得性心律失常。本文从门控机制及功能、HERG通道相关的心律失常、药物与通道相互作用机制、优化通道靶点的策略等四个方面综述IKr/HERG通道在抗心律失常方面的最新研究进展。

Rapidly activating component of delayed rectifier potassium current （IKr） plays a key role in the repolarization phase of cardiac action potential. Human ether-a-go-go-related gene （HERG） encodes the α subunit of this potassium channel. Mutations of HERG gene induce genetic long QT syndrome （LQTS）. Furthermore, IKr/HERG is the target of some drugs which may cause cardiac QT interval prolongation. Some other drugs with different chemical structures also may block the channel and prolong QT interval, which even developed into acquired arrhythmias. This review summarized the recent progress of structure, gating mechanisms and functions of IKr/HERG channel, IK/HERG related arrhythmias, interaction between K ^＋ channel and drugs, and strategies of grading-up the IKr/HERG target.