Abstract 11919: AMP-Activated Protein Kinase Response to Metabolic Stress: A Novel Determinant of Atrial Fibrillation Progression

Introduction: Metabolic stress is observed in clinical and experimental atrial fibrillation (AF). Metabolic stress activates AMP-dependent protein kinase (AMPK) via phosphorylation; activated AMPK produces compensatory changes in the determinants of energy balance. Here, we examined AMPK responses in AF and their role in remodeling responses of atrial Ca2+ handling and contractility. Methods: AMPK and Cav1.2 protein were quantified by immunoblot. Ca2+ transients (CaTs, Indo1 AM), cell shortening (CS, videometry), L-type Ca2+ (ICa,L) and NCX (INCX) current (patch clamp) were measured in dog left atrial (LA) cardiomyocytes (CMs) under metabolic stress due to glycolysis inhibition (GI, 10 mM 2-deoxyglucose/10 mM pyruvate). Results: In dogs with 1-wk electrically-maintained AF (n=4), the phosphorylation ratio (PhR) of AMPK (indicating activation) increased in LA by 101%* (*p<0.05) vs. controls (n=4). Metabolic stress due to GI in 2 Hz paced LA CMs increased AMPK PhR by 103%* vs. quiescent CMs. In 2 Hz paced c...