Clustering properties of the cardiac ryanodine receptor in health and heart failure.

The cardiac ryanodine receptor (RyR2) is an intracellular Ca release channel vital for the function of the heart. Physiologically, RyR2 is triggered to release Ca from the sarcoplasmic reticulum (SR) which enables cardiac contraction; however, spontaneous Ca leak from RyR2 has been implicated in the pathophysiology of heart failure (HF). RyR2 channels have been well documented to assemble into clusters within the SR membrane, with the organisation of RyR2 clusters recently gaining interest as a mechanism by which the occurrence of pathological Ca leak is regulated, including in HF.

Direct regulation of the cardiac ryanodine receptor (RyR2) by O-GlcNAcylation.

Background: O-GlcNAcylation is the enzymatic addition of a sugar, O-linked β-N-Acetylglucosamine, to the serine and threonine residues of proteins, and is abundant in diabetic conditions. We have previously shown that O-GlcNAcylation can trigger arrhythmias by indirectly increasing pathological Ca leak through the cardiac ryanodine receptor (RyR2) via Ca/calmodulin-dependent kinase II (CaMKII). However, RyR2 is well known to be directly regulated by other forms of serine and threonine modification, therefore, this study aimed to determine whether RyR2 is directly modified by O-GlcNAcylation and if this also alters the function of RyR2 and Ca leak.

The function and regulation of calsequestrin-2: implications in calcium-mediated arrhythmias.

Unlabelled: Cardiac arrhythmias are life-threatening events in which the heart develops an irregular rhythm. Mishandling of Ca within the myocytes of the heart has been widely demonstrated to be an underlying mechanism of arrhythmogenesis. This includes altered function of the ryanodine receptor (RyR2)-the primary Ca release channel located to the sarcoplasmic reticulum (SR).