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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 inward rectifier potassium channel (IK1 channel) in mammalian atrial and ventricular muscles is the major conductance of the resting potential of cells and participates in the formation of bipolar repolarization current at the action potential. Therefore, IK1 plays an important role in the regulation of myocardial resting potentials, which in turn affects the cardiac excitability and arrhythmia. This review summarizes the basic characteristics of IK1 channel, its inward rectification mechanism and the formation of channel molecular subunits. It also discusses the role of IK1 channel in the occurrence of ventricular myocyte excitability and arrhythmia, and the possibility of modulation of IK1 channel to inhibit arrhythmia. In fact, blocking or enhancing IK1 may have anti-arrhythmic effects, but also the risk of arrhythmia. Action potential duration prolongation is a well-established mechanism of anti-arrhythmia. Evidence suggests that blockade of IK1 prolongs action potential duration and exhibits antiarrhythmic effects in animal models of arrhythmias, but so far these studies have not led to specific IK1 Blockers come out. Drug safety has always been the primary reason, therefore, the prospects for the application of IK1 blockers are worrisome. In contrast, the latest findings show that moderately excited IK1 restores resting potentials depolarized due to lesion lesion, which can effectively reduce the incidence of certain ventricular arrhythmias.