NeuroSearch A/S, Ballerup, and Danish National Research Foundation Centre for Cardiac Arrhythmia, University of Copenhagen, Denmark.
Acta Physiol (Oxf). 2010 Feb;198 Suppl 676:1-48. doi: 10.1111/j.1748-1716.2009.02072.x.
The cardiac action potential can be divided into five distinct phases designated phases 0-4. The exact shape of the action potential comes about primarily as an orchestrated function of ion channels. The present review will give an overview of ion channels involved in generating the cardiac action potential with special emphasis on potassium channels involved in phase 3 repolarization. In humans, these channels are primarily K(v)11.1 (hERG1), K(v)7.1 (KCNQ1) and K(ir)2.1 (KCNJ2) being the responsible alpha-subunits for conducting I(Kr), I(Ks) and I(K1). An account will be given about molecular components, biophysical properties, regulation, interaction with other proteins and involvement in diseases. Both loss and gain of function of these currents are associated with different arrhythmogenic diseases. The second part of this review will therefore elucidate arrhythmias and subsequently focus on newly developed chemical entities having the ability to increase the activity of I(Kr), I(Ks) and I(K1). An evaluation will be given addressing the possibility that this novel class of compounds have the ability to constitute a new anti-arrhythmic principle. Experimental evidence from in vitro, ex vivo and in vivo settings will be included. Furthermore, conceptual differences between the short QT syndrome and I(Kr) activation will be accounted for.
心肌动作电位可分为五个不同的阶段，分别为 0-4 期。动作电位的确切形态主要是由离子通道的协调功能产生的。本综述将概述参与产生心肌动作电位的离子通道，特别强调参与 3 期复极化的钾通道。在人类中，这些通道主要是 K(v)11.1（hERG1）、K(v)7.1（KCNQ1）和 K(ir)2.1（KCNJ2），它们是传导 I(Kr)、I(Ks)和 I(K1)的负责的α亚基。将介绍分子成分、生物物理特性、调节、与其他蛋白质的相互作用以及与疾病的关系。这些电流的功能丧失和获得都与不同的心律失常疾病有关。因此，本综述的第二部分将阐明心律失常，随后将重点介绍具有增加 I(Kr)、I(Ks)和 I(K1)活性的新开发的化学实体。将评估这一类新化合物是否具有构成新的抗心律失常原理的能力。将包括来自体外、离体和体内研究的实验证据。此外，还将说明短 QT 综合征和 I(Kr)激活之间的概念差异。
