Inhibition of CaMKII phosphorylation of RyR2 prevents inducible ventricular arrhythmias in mice with Duchenne muscular dystrophy.

ABSTRACT:

Background

Ventricular tachycardia (VT) is the second most common cause of death in patients with Duchenne muscular dystrophy (DMD). Recent studies have implicated enhanced sarcoplasmic reticulum (SR) Ca(2+) leak via type 2 ryanodine receptor (RyR2) as a cause of VT in the mdx mouse model of DMD. However, the signaling mechanisms underlying induction of SR Ca(2+) leak and VT are poorly understood.

Objective

To test whether enhanced Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) phosphorylation of RyR2 underlies SR Ca(2+) leak and induction of VT in mdx mice.

Methods

Programmed electrical stimulation was performed on anesthetized mice and confocal imaging of Ca(2+) release events in isolated ventricular myocytes.

Results

Programmed electrical stimulation

SUBMITTER: Ather S 

PROVIDER: S-EPMC3605194 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature