Electrical Remodeling in Pressure-Overload Cardiac Hypertrophy Role of Calcineurin

Background Myocyte hypertrophy accompanies many forms of heart disease, but its contribution to electrical remodeling is unknown. Methods and Results We studied mouse hearts subjected to pressure overload by surgical thoracic aortic banding. In unbanded control hearts, action potential duration (APD) was significantly longer in subendocardial myocytes compared with subepicardial myocytes. Hypertrophy-associated APD prolongation was significantly greater in subendocardial myocytes compared with subepicardial myocytes, indicating stress-induced amplification of repolarization dispersion. To investigate the underlying basis, we performed voltage-clamp recordings on dissociated myocytes. Under control unoperated conditions, subendocardial myocytes exhibited significantly less transient outward current (Ito) than did subepicardial cells. Hypertrophy was not associated with significant changes in Ito, sustained current, or inward rectifier current densities, but peak L-type Ca2+ current density (ICa,L) increase...