Zhang Xiao-Dong, Lieu Deborah K, Chiamvimonvat Nipavan
Division of Cardiovascular Medicine, Department of Internal Medicine, University of California, Davis, California.
Division of Cardiovascular Medicine, Department of Internal Medicine, University of California, Davis, California.
Heart Rhythm. 2015 Aug;12(8):1845-51. doi: 10.1016/j.hrthm.2015.04.046. Epub 2015 May 5.
Small-conductance Ca2+ -activated K+ (SK, KCa2) channels are unique in that they are gated solely by changes in intracellular Ca2+ and, hence, function to integrate intracellular Ca2+ and membrane potentials on a beat-to-beat basis. Recent studies have provided evidence for the existence and functional significance of SK channels in the heart. Indeed, our knowledge of cardiac SK channels has been greatly expanded over the past decade. Interests in cardiac SK channels are further driven by recent studies suggesting the critical roles of SK channels in human atrial fibrillation, the SK channel as a possible novel therapeutic target in atrial arrhythmias, and upregulation of SK channels in heart failure in animal models and in human heart failure. However, there remain critical gaps in our knowledge. Specifically, blockade of SK channels in cardiac arrhythmias has been shown to be both antiarrhythmic and proarrhythmic. This contemporary review provides an overview of the literature on the role of cardiac SK channels in cardiac arrhythmias and serves as a discussion platform for the current clinical perspectives. At the translational level, development of SK channel blockers as a new therapeutic strategy in the treatment of atrial fibrillation and the possible proarrhythmic effects merit further considerations and investigations.
小电导Ca2+激活K+（SK，KCa2）通道的独特之处在于，它们仅由细胞内Ca2+的变化门控，因此其功能是在逐搏基础上整合细胞内Ca2+和膜电位。最近的研究为心脏中SK通道的存在及其功能意义提供了证据。事实上，在过去十年中，我们对心脏SK通道的了解有了极大的扩展。最近的研究表明SK通道在人类心房颤动中起关键作用，SK通道可能是心房心律失常的新型治疗靶点，以及动物模型和人类心力衰竭中心脏SK通道上调，这些进一步推动了对心脏SK通道的研究兴趣。然而，我们的知识仍存在关键空白。具体而言，已证明在心律失常中阻断SK通道既有抗心律失常作用，也有致心律失常作用。这篇当代综述概述了关于心脏SK通道在心律失常中作用的文献，并作为当前临床观点的讨论平台。在转化层面，将SK通道阻滞剂开发为治疗心房颤动的新治疗策略以及可能的致心律失常作用值得进一步考虑和研究。
