摘要
哺乳动物心房肌和心室肌的内向整流钾通道(IK1通道)是细胞静息电位的主要电导,并参与动作电位复极末期复极电流的形成。因此,IK1对心肌静息电位有重要的调控作用,并进而影响心肌的兴奋性和心律失常的发生。本文综述了IK1通道的基本特性,它的内向整流机制和通道分子亚单位的构成;讨论了IK1通道在心室肌兴奋性和心律失常发生中的作用,以及调制IK1通道抑制心律失常的可能性。事实上,阻断或增强IK1都可能具有抗心律失常作用,也同时存在致心律失常的风险。动作电位时程延长是一个公认的抗心律失常机制,有证据表明,在心律失常动物模型,阻断IK1可延长动作电位时程并显示抗心律失常效应,但是这些研究迄今并未使特异性IK1阻断剂问世。药物的安全性一直是首要原因,因此,IK1阻断剂的应用前景堪忧。与此相反,最新研究结果显示,适度激动IK1,恢复因病变损伤而去极化的静息电位,可有效减少某些室性心律失常的发生。
The cardiac inwardly rectifying potassium channel （IK1 ）, which is mainly expressed in mammalian atrial and ventricular myocytes, has been considered as the primary conductance controlling the resting potential （RP） and permitting a significant repolarizing current during the terminal phase of action potential. Therefore, IK1 is highly influential on the RP, and the modulation of IK1 would likely have profound effects on cardiac excitability and arrhythmogenesis. This article may shed light on the fundamental properties of cardiac IK1 , the mechanisms of inward rectification and IK1 subunits composition. Furthermore, the article discusses the role of IK1 in ventricular excitability and arrhythmogenesis and explores the possibility of modulating IK1 as an antiarrhythmic mechanism. In fact, both blocking and enhancing IK1 could be antiarrhythmic, but have proarrhythmic potential at the same time. Action potential duration （APD） prolongation has been accepted as an important antiarrhythmic strategy with some evidence in animal models of arrhyth-mogenesis that IK1 blockade can prolongate APD and be antiarrhythmic. However, the potential of IK1 blockade has not resulted in the development of specific IK1 blockers used clinically. Safety concerns are probably the main reason, and the therapeutic potential for IK1 blockers seems somewhat small. On the contrary, the up to date reports indicate that moderately activating IK1 and hyperpolarizing the RP which has been depolarized by pathologic injury are to be feasible and effective to alleviate some kinds of ventricular arrhythmias.
出处
《生理学报》
CAS
CSCD
北大核心
2012年第6期751-757,共7页
Acta Physiologica Sinica
基金
supported by the National Natural Science Foundation of China (No.30840038)
the Specialized Research Fund for the Doctoral Program of Chinese Higher Education (No.200801140001)
the Natural Science Foundation of Shanxi Province
China (No.2009021043-2)
关键词
钾通道
心律失常
整流作用
potassium channel
arrhythmia
rectification
