CARDIAC POTASSIUM CHANNEL SUBUNITS AND SUDDEN DEATH

描述 (根据申请者摘要改编)背景：心脏性猝死是一种 这是美国心血管疾病死亡的重要原因。《长河》 QT综合征(LQT)是一种与室性疾病相关的遗传性疾病 心律失常和猝死。KVLQT1基因的突变导致了大多数 继承的LQT的常见形式。KvLQT1蛋白与一种调节基因共组装 形成缓慢激活的心脏延迟整流(IKs)的亚基 频道。IKs是心脏复极的重要调节器，AS 这样，iKs的减少可能会促进心律失常的易感性。 这个提议的目标是：(1)表征分子 Iks通道亚基之间的相互作用和(2)定义分子 KVLQT1和hminK基因LQT相关突变的发病机制这些研究 将使用克隆的人水貂和KvLQT1蛋白进行异源实验 在非洲爪哇卵母细胞中表达。 意义：深入了解肺气郁结证的分子发病机制 钾离子通道调控的分子机制将促进心肌梗死的发生 威胁生命的心律失常的新治疗策略。 环境：犹他大学是一所卓越的研究机构 心脏离子通道研究领域和LQT的分子遗传学。

DESCRIPTION (Adapted from applicants' abstract) Background: sudden cardiac death is an important cause of cardiovascular mortality in the United States. The long QT syndrome (LQT) is an inherited disorder associated with ventricular arrhythmias and sudden death. Mutations in the gene KVLQT1 cause the most common form of inherited LQT. KvLQT1 proteins coassemble with a regulatory subunit, minK, to form the slowly activating cardiac delayed rectifier (Iks) channel. Iks is an important modulator of cardiac repolarization, and as such, reductions in Iks may promote arrhythmia susceptibility. The goals of this proposal are: (1) To characterize the molecular interactions between Iks channel subunits and (2) To define the molecular pathogenesis of LQT-associated mutations in KVLQT1 and hminK. The studies will be performed using cloned human minK and KvLQT1 proteins heterologously expressed in Xenopus oocytes. Significance: Insight into the molecular pathogenesis of LQT and the molecular mechanisms of K+ channel regulation will facilitate development of novel treatment strategies for life-threatening arrhythmias. Environment: The University of Utah is a preeminent research institution in the field of cardiac ion channel research and the molecular genetics of LQT.