Atrial arrhythmogenesis in catecholaminergic polymorphic ventricular tachycardia – is there a mechanistic link between sarcoplasmic reticulum Ca2+ leak and re‐entry?

Abstract

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is caused by mutations in the genes encoding the cardiac ryanodine receptor channel (RyR2) or the major sarcoplasmic reticulum (SR) Ca2+ buffer calsequestrin-2 (Casq2) (Leenhardt et al., 2012). Traditionally, CPVT has been described as a bi-directional or polymorphic ventricular arrhythmia occurring during conditions of increased sympathetic tone, which may originate from ectopic activity due to abnormal (sub)cellular Ca2+ handling (Leenhardt et al., 2012). Recent studies, however, have suggested that CPVT mutations in RyR2 are also associated with atrial arrhythmias. In this edition of Acta Physiologica, King et al. (King et al., 2012) show for the first time that atria from mice homozygous for the CPVT-associated mutation P2328S in RyR2 (RyR2S/S) have a reduced conduction velocity (CV) and lower maximum rates of action potential (AP) upstroke velocity compared to wild-type (WT) mice. Moreover, these parameters correlated strongly with arrhythmia susceptibility suggesting a potential novel arrhythmogenic mechanism due to RyR2 mutations.