Phosphorylation of the cardiac ryanodine receptor by Ca2+/calmodulin-dependent protein kinase II: the dominating twin of protein kinase A?

Excitation–contraction coupling in the heart relies on Ca -induced Ca release from the sarcoplasmic reticulum (SR). Ca influx via L-type Ca channels during an action potential triggers Ca release from the SR via Ca release channels, or ryanodine receptors (RyR2). Fine tuning of RyR2-mediated SR Ca release is central to cardiac function. When RyR2-mediated Ca release increases, the resulting augmentation of the [Ca ]i transient causes increased contraction. Uncontrolled openings of RyR2 during diastole, on the other hand, may elicit delayed afterdepolarizations and arrhythmias. Dysfunction of RyR2 may occur under certain pathological conditions, eg, excess sympathetic stimulation, and may contribute to such cardiac diseases as heart failure1 or atrial fibrillation.2 Furthermore, mutations in RyR2 can cause stress-induced ventricular tachycardias and sudden death in otherwise healthy individuals.3 Thus, proper regulation and function of RyR2 is essential for adequate cardiac function.