Cardiac Resynchronization Therapy Reduces Subcellular Heterogeneity of Ryanodine Receptors, T-Tubules, and Ca ²⁺ Sparks Produced by Dyssynchronous Heart Failure

Abstract

RyR density exhibits remarkable subcellular heterogeneity in DHF. RyR remodeling occurred in lateral and anterior cardiomyocytes, but remodeling of t-system was confined to lateral myocytes. These findings indicate that different mechanisms underlie remodeling of RyRs and t-system. Furthermore, we suggest that ventricular dyssynchrony exacerbates subcellular remodeling in heart failure. CRT efficiently reduced subcellular heterogeneity. These results will help to explain remodeling of excitation-contraction coupling in disease and restoration after CRT.