Hyperactive ryanodine receptors in human heart failure and ischaemic cardiomyopathy reside outside of couplons

Abstract

In HF and after MI, RyR microdomain re-organization enhances spontaneous Ca2+ release at non-coupled sites in a manner dependent on CaMKII activation and mito-ROS production. This specific modulation generates a substrate for arrhythmia that appears to be responsive to selective pharmacologic modulation.