Abstract 16944: Cx43 Hemichannel Inhibition Prevents Arrhythmias in Duchenne Muscular Dystrophy Mice

Duchenne muscular dystrophy (DMD) is a fatal disease characterized by skeletal and cardiac muscle pathologies due to the absence of the membrane stabilizing protein dystrophin. Although most research has focused on skeletal muscle, 100% of patients over the age of 18 are diagnosed with cardiomyopathy, associated with the development of arrhythmias and eventual heart failure. The connexin proteins, normally responsible for the formation of gap junctions, are known to play a significant role in cardiac conduction. Remodeling of these proteins has been linked to the development of arrhythmias following myocardial infarction. Through analysis of Cx43, the most abundant connexin in the heart, we found that both mild mdx and severe mdx:utr(-/-) models of DMD display significant protein upregulation and mislocalization to the lateral sides of cardiomyocytes. Interestingly, this pattern is more extreme in the severe model, consistent with the degree of cardiac phenotype. To assess the role of Cx43 in DMD arrhythm...