Abnormal termination of Ca2+ release is a common defect of RyR2 mutations associated with cardiomyopathies.

ABSTRACT:

Rationale

Naturally occurring mutations in the cardiac ryanodine receptor (RyR2) have been associated with both cardiac arrhythmias and cardiomyopathies. It is clear that delayed afterdepolarization resulting from abnormal activation of sarcoplasmic reticulum Ca2+ release is the primary cause of RyR2-associated cardiac arrhythmias. However, the mechanism underlying RyR2-associated cardiomyopathies is completely unknown.

Objective

In the present study, we investigate the role of the NH2-terminal region of RyR2 in and the impact of a number of cardiomyopathy-associated RyR2 mutations on the termination of Ca2+ release.

Methods and results

The 35-residue exon-3 region of RyR2 is associated with dilated cardiomyopathy. Single-cell luminal Ca2+ imaging revealed that the de

SUBMITTER: Tang Y 

PROVIDER: S-EPMC3345272 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature