Electrical remodeling contributes to complex tachyarrhythmias in connexin43-deficient mouse hearts

摘要: Loss of connexin43 (Cx43) gap junction channels in the heart results a marked increase incidence spontaneous and inducible polymorphic ventricular tachyarrhythmias (PVTs). The mechanisms resulting this phenotype remain unclear. We hypothesized that uncoupling promotes regional ion channel remodeling, thereby increasing electrical heterogeneity facilitating development PVT. In isolated-perfused control hearts, programmed stimulation elicited infrequent monomorphic (MVT), dominant frequencies (DFs) during MVT were similar right ventricle (RV) left (LV). Moreover, conduction properties, action potential durations (APDs), repolarizing current densities RV LV myocytes. contrast, PVT was common Cx43 conditional knockout (OCKO) arrhythmias characterized by significantly higher DFs compared to LV. APDs OCKO myocytes shorter than those from chamber-matched controls, with being most affected. APD shortening associated levels sustained both chambers as well inward rectifier only Thus, alterations cell-cell coupling lead changes potassium expression, which case facilitates reentrant arrhythmias. propose new mechanistic link between remodeling. These findings may be relevant not cardiac tissue but also other organ systems where remodeling is known occur.