Role of RyR2 posttranslational modification in arrhythmias

Cardiac arrhythmias remain the leading cause of death in patients with heart disease. An important trigger for arrhythmias is the inappropriate opening of the cardiac ryanodine receptor (RyR2). However, the mechanism by which these openings occur is not well understood. Phosphorylation is typically thought to increase the inappropriate opening of RyR2. However, we have preliminary evidence of a novel phosphorylation event that suppresses RyR2 function and protects against arrhythmias. Using protein biochemistry, biophysics, advanced imaging in ventricular myocytes and ECG measurements in transgenic animals; this project proposes to determine how this phosphorylation event controls RyR2 function.