RYR2 and Ventricular arrhythmia: In general ventricular arrhythmias are initiated and maintained by either focal (ectopic) or re-entry mechanisms, which have been linked to increased diastolic SR Ca2+ leak from RyR2 and subsequent activation of the Na+/Ca2+-exchanger (NCX) at the cellular level (Weiss et al., 2000; Jalife et al., 2003; Prystowsky et al., 2012; Qu and Weiss, 2015).