FHFs and Cardiac Electrophysiology

项目摘要 心脏病仍然是美国和其他发达国家的主要死亡原因。半年 这些死亡是突然发生的，通常是由于急性心肌梗塞时出现的室性快速性心律失常。 缺血、获得性心脏病或遗传综合征，包括通道病和心肌病。 尽管进行了数十年的研究，但我们对相关分子机制的理解存在重大差距 对于正常的心脏节律，以及增加节律紊乱风险的异常。我们 实验室已经鉴定出称为成纤维细胞生长因子同源因子（FHF）的分子， 调节心律。在没有FHF的情况下，心脏会发生严重的传导疾病和心律失常。 在本申请中，我们提出了一系列旨在了解机制的实验， FHF蛋白的缺乏导致这些疾病表现。

PROJECT SUMMARY Heart disease remains the leading cause of death in the United States and other developed countries. Half of these deaths occur suddenly, typically from ventricular tachyarrhythmias that arise in the setting of acute ischemia, acquired heart disease or inherited syndromes including channelopathies and cardiomyopathies. Despite decades of research, major gaps exist in our understanding of the molecular mechanisms responsible for normal cardiac rhythmicity, as well as abnormalities that increase the risk of rhythm disturbances. Our laboratory has identified molecules, known as fibroblast growth factor homologous factors (FHFs), that potently regulate heart rhythm. In the absence of FHFs, hearts develop significant conduction disease and arrhythmias. In this application we propose a series of experiments designed to understand the mechanisms through which deficiency of FHF proteins results in these disease manifestions.