Recent molecular insights from mutated IKS channels in cardiac arrhythmia
Recent molecular insights from mutated IKS channels in cardiac arrhythmia
复制标题
DOI：
10.1016/j.coph.2013.12.004
复制
发表时间：
2014-04-01
影响因子：
4
通讯作者：
Attali, Bernard
中科院分区：
文献类型：
--
作者：
Dvir, Meidan;Peretz, Asher;Attali, Bernard
KCNQ 1与KCNE 1的共组装产生I-KS钾电流，该电流对于心脏动作电位的适当复极化至关重要。KCNQ 1或KCNE 1基因的突变会导致危及生命的心律失常，引起长QT综合征、短QT综合征、窦性心动过缓和心房颤动。最近的研究结果开始提供一个图片的功能获得性和功能丧失性突变是如何与临床多效性心脏表型。在这篇综述中，我们讨论了最近的分子的见解，从突变改变不同的结构模块的通道复合物是必要的适当的I-KS功能。我们提出了可能的分子机制的突变损害的电压传感功能，以及那些改变的通道调节磷脂酰肌醇-4，5-二磷酸，钙调蛋白和蛋白激酶A。我们还讨论了疾病的I-KS通道的意义，充分的药理学靶向心律失常。
Co-assembly of KCNQ1 with KCNE1 generates the I-KS potassium current that is vital for the proper repolarization of the cardiac action potential. Mutations in either KCNQ1 or KCNE1 genes lead to life-threatening cardiac arrhythmias causing long QT syndrome, short QT syndrome, sinus bradycardia and atrial fibrillation. Findings emerging from recent studies are beginning to provide a picture of how gain-of-function and loss-of-function mutations are associated with pleiotropic cardiac phenotypes in the clinics. In this review, we discuss recent molecular insights obtained from mutations altering different structural modules of the channel complex that are essential for proper I-KS function. We present the possible molecular mechanisms underlying mutations impairing the voltage sensing functions, as well as those altering the channel regulation by phosphatidylinositol-4,5-bisphosphate, calmodulin and protein kinase A. We also discuss the significance of diseased I-KS channels for adequate pharmacological targeting of cardiac arrhythmias.