Gating pore current is a novel biophysical defect of Nav1.5 mutations associated with unusual cardiac arrhythmias and dilation

摘要

Dilated cardiomyopathy (DCM) is the most common cause of heart failure (HF) in North America. It provokes the dilatation of cardiac cavities and impairs contractility and systolic function. DCM accounts for over 90% of all cardiomyopathy cases referred to specialized centers and is collectively the most common reason for heart transplants in the young. Familial or genetically related DCM makes up 20-35% of all DCM cases [1]. Most genes associated with DCM encode structural proteins involved in contractile function and the cytoskeletal matrix. Mutations in these genes are believed to decrease the overall structural integrity of myocytes, leading to cell disarray, the development of fibrosis characteristic of DCM and myocyte death [2].