Cardiac BIN1 folds T-tubule membrane, controlling ion flux and limiting arrhythmia.

摘要: Cardiomyocyte T tubules are important for regulating ion flux. Bridging integrator 1 (BIN1) is a T-tubule protein associated with calcium channel trafficking that downregulated in failing hearts. Here we find cardiac normally contain dense protective inner membrane folds formed by isoform of BIN1. In mice Bin1 deletion, folding decreased, which does not change overall cardiomyocyte morphology but leads to free diffusion local extracellular and potassium ions, prolonging action-potential duration increasing susceptibility ventricular arrhythmias. We also found rescued expression the BIN1 BIN1+13+17, promotes N-WASP-dependent actin polymerization stabilize at Z discs. BIN1+13+17 recruits fold membrane, creating 'fuzzy space' protectively restricts When amount as occurs acquired cardiomyopathy, altered, arrhythmia can result.