Abstract 15361: Loss of Caveolin-3 Disrupts Mouse Sinoatrial Node Pacemaking and Stimulates Atrial Arrhythmogenesis

Introduction: Caveolae represent a population of caveolin-3 (Cav3)-containing membrane microdomains housing a number of ion channels and transporters that are involved in sinoatrial node (SAN) pacemaking. Cav3 organizes these channels within macromolecular signaling complexes providing highly localized autonomic regulation of the SAN. Hypothesis: Cav3 is required for functional integrity of the SAN, synchronizing Ca release and Ca-voltage coupling. Methods: ECG telemetry, simultaneous optical mapping of voltage and Ca in whole hearts and isolated atria, and Ca imaging of isolated atrial myocyte were applied to wild type (WT, n=8) and Cav3 knockout (KO, n=8) mice, at baseline and under isoproterenol (Iso). Results: Though no difference in average heart rate (HR) was revealed between groups, KO mice showed significant beat-to-beat HR variability, both in vivo and in vitro (9.4 ± 2.4% from HR in KO vs. 2.2 ± 1.1% in WT, P<0.01). Optical mapping linked the increased HR variability to enhanced ectopic foci out...