Ca2激活的K通道对细胞Ca2稳态和兴奋性至关重要;它们耦合细胞内Ca2和膜电压变化。其中,小的,4-14pS,电导SK通道包括三个,KCNN1-3编码,SK1/KCa2.1,SK2/KCa2.2和SK3/KCa2.3,具有特征性的通道亚型,EC50≈10nM,40pM,1nM,阿帕明敏感性。所有SK通道,特别是SK2通道,在心房中表达,心室和传导系统心肌细胞。药理学和基因修饰结果表明,SK通道阻断或敲除延长了动作电位持续时间(APD)和有效不应期(ERPs),特别是在心房中,而且在心室,和窦房,房室结和浦肯野肌细胞,相应地影响心律失常倾向。此外,线粒体SK通道可以减少线粒体Ca2+过载和活性氧的产生。SK通道显示低电压,但明显的Ca2+依赖性(EC50~300-500nM)反映其α-亚基钙调蛋白(CaM)结合域,它们可以通过电压门控或ryanodine受体Ca2通道活性被激活。SK功能还取决于复杂的运输和表达过程以及与来自不同SK亚型的其他离子通道或亚基的关联。心房和心室临床心律失常发生可能通过减少或增加APD相应地加速和稳定折返性转子或增加触发活动的发生率来增加或减少SK表达。本文是“心跳:其分子基础和生理机制”主题问题的一部分。
Ca2+-activated K+ channels are critical to cellular Ca2+ homeostasis and excitability; they couple intracellular Ca2+ and membrane voltage change. Of these, the small, 4-14 pS, conductance SK channels include three, KCNN1-3 encoded, SK1/KCa2.1, SK2/KCa2.2 and SK3/KCa2.3, channel subtypes with characteristic, EC50 ∼ 10 nM, 40 pM, 1 nM, apamin sensitivities. All SK channels, particularly SK2 channels, are expressed in atrial, ventricular and conducting system cardiomyocytes. Pharmacological and genetic modification results have suggested that SK channel block or knockout prolonged action potential durations (APDs) and effective refractory periods (ERPs) particularly in atrial, but also in ventricular, and sinoatrial, atrioventricular node and Purkinje myocytes, correspondingly affect arrhythmic tendency. Additionally, mitochondrial SK channels may decrease mitochondrial Ca2+ overload and reactive oxygen species generation. SK channels show low voltage but marked Ca2+ dependences (EC50 ∼ 300-500 nM) reflecting their α-subunit calmodulin (CaM) binding domains, through which they may be activated by voltage-gated or ryanodine-receptor Ca2+ channel activity. SK function also depends upon complex trafficking and expression processes and associations with other ion channels or subunits from different SK subtypes. Atrial and ventricular clinical arrhythmogenesis may follow both increased or decreased SK expression through decreased or increased APD correspondingly accelerating and stabilizing re-entrant rotors or increasing incidences of triggered activity. This article is part of the theme issue \'The heartbeat: its molecular basis and physiological mechanisms\'.