Purkinje Cells and Arrhythmia Mechanisms

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。 专门的心脏传导系统(CCS)包括一个不同种类的细胞网络，这些细胞协调 心肌电兴奋波在整个心肌中的启动和传播积累 有证据表明，心室传导系统(VCS)功能障碍起着关键的机制作用。 引发了一系列危及生命的室性心律失常，然而在我们的 了解血管紧张素转换酶的形成、功能和功能障碍的分子机制 风投公司。我们的实验室已经建立了新的工具，并发现了我们假设的新基因和新途径 对VCS的形成、功能和功能障碍至关重要。在本申请中，我们提出了一系列实验 旨在测试这些新基因和途径的生物学重要性。

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. The specialized cardiac conduction system (CCS) comprises a heterogeneous network of cells that orchestrate the initiation and propagation of a wave of electrical excitation throughout the myocardium. Accumulating evidence suggests that dysfunction of the ventricular conduction system (VCS) plays a key mechanistic role triggering a broad range of life-threatening ventricular arrhythmias, however major gaps exist in our understanding of the molecular mechanisms responsible for the formation, function and dysfunction of the VCS. Our laboratory has established new tools and identified novel genes and pathways that we hypothesize are critical for VCS formation, function and dysfunction. In this application we propose a series of experiments designed to test the biological importance of these new genes and pathways.