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AIM: RyR2 mutations are associated with catecholaminergic polymorphic tachycardia, a condition characterized by ventricular and atrial arrhythmias. The present experiments investigate the atrial electrophysiology of homozygotic murine RyR2-P2328S (RyR2(S/S)) hearts for ectopic triggering events and for conduction abnormalities that might provide a re-entrant substrate. METHODS: Electrocardiograph recordings were made from regularly stimulated RyR2(S/S) and wild type (WT) hearts, perfused using a novel modified Langendorff preparation. This permitted the simultaneous use of either floating intracellular microelectrodes to measure action potential (AP) parameters, or a multielectrode array to measure epicardial conduction velocity (CV). RESULTS: RyR2(S/S) showed frequent sustained tachyarrhythmias, delayed afterdepolarizations and ectopic APs, increased interatrial conduction delays, reduced epicardial CVs and reduced maximum rates of AP depolarization ((dV/dt)(max)), despite similar effective refractory periods, AP durations and AP amplitudes. Effective interatrial CVs and (dV/dt)(max) values of APs following ectopic (S2) stimulation were lower than those of APs following regular stimulation and decreased with shortening S1S2 intervals. However, although RyR2(S/S) atria showed arrhythmias over a wider range of S1S2 intervals, the interatrial CV and (dV/dt)(max) of S2 APs provoking such arrhythmias were similar in RyR2(S/S) and WT. CONCLUSIONS: These results suggest that abnormal intracellular Ca(2+) homoeostasis produces both arrhythmic triggers and a slow-conducting arrhythmic substrate in RyR2(S/S) atria. A similar mechanism might also contribute to arrhythmogenesis in other conditions, associated with diastolic Ca(2+) release, such as atrial fibrillation.

Original publication

DOI

10.1111/apha.12006

Type

Journal article

Journal

Acta Physiol (Oxf)

Publication Date

02/2013

Volume

207

Pages

308 - 323

Keywords

Action Potentials, Animals, Arrhythmias, Cardiac, Calcium, Electrocardiography, Heart Atria, Mice, Mice, Mutant Strains, Organ Culture Techniques, Ryanodine Receptor Calcium Release Channel