Elucidating the Mechanisms for Arrhythmogenicity in Ventricular Myocytes From Alpha MHC403/+ Hypertrophic Hearts

摘要: Sudden cardiac death is a tragic and devastating complication in patients with inherited heart disease that frequently occurs with increased sympathetic stimulation. Familial hypertrophic cardiomyopathy is a primary disorder of the myocardium characterised by cardiac hypertrophy due to mutations in the genes encoding sarcomeric proteins, such as the cardiac myosin heavy chain protein (MHC). Morphological changes include myocyte hypertrophy, myofibrillar disarray, and fibrosis. Although differences in cardiac function are well described, the exact mechanism contributing to the increased arrhythmogenicity is poorly understood. We performed electrophysiology studies in myocytes from 40 week old heterozygous αMHC403/+ mice expressing the human disease-causing mutation Arg403Gln. At low-frequency stimulation (1 Hz) extra action potentials were common in mutant but absent in negatively genotyped (wt …