Ca2+ release channels (Ryanodine receptors) and arrhythmogenesis

Abstract

Intracellular calcium (Ca2+) release channels (ryanodine receptors type 2, RyR2) are present on the sarcoplasmic reticulum (SR) in cardiomyocytes and are required for excitation-contraction coupling in cardiac muscle. RyR2s are macromolecular channel complexes associated with regulatory proteins that modulate RyR2 function in response to extracellular signals. Recent studies have provided new mechanistic insight into the role of diastolic SR Ca2+ leak through RyR2 as a trigger for a wide range of cardiac arrhythmias. RyR2 has been implicated to play a central role in arrhythmias associated with catecholaminergic polymorphic ventricular tachycardia (CPVT), heart failure (HF) and drug-induced arrhythmias. At present, there is no FDA approved medication that selectively targets RyR2. However, novel therapeutic approaches are being evaluated to correct defective RyR2 Ca2+ release based on recent advances in the understanding of the cellular mechanisms underlying arrhythmias in HF and CPVT.