FHFs and Cardiac Electrophysiology

项目总结 在美国和其他发达国家，心脏病仍然是主要的死亡原因。一半的人 这些死亡发生得很突然，通常是由急性心肌梗塞时出现的室性心动过速引起的。 缺血、获得性心脏病或遗传性综合征，包括经络病和心肌病。 尽管经过了几十年的研究，但在我们对相关分子机制的理解上仍存在重大差距 对于正常的心律失常，以及增加心律紊乱风险的异常。我们的 实验室已经确定了一种被称为成纤维细胞生长因子同源因子(FHFs)的分子，它可以有效地 调节心率。在没有FHFs的情况下，心脏会出现严重的传导性疾病和心律失常。 在本申请中，我们提出了一系列实验，旨在了解通过这些机制 缺乏FHF蛋白会导致这些疾病的表现。

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.