Atrial arrhythmia, triggering events and conduction abnormalities in isolated murine RyR2-P2328S hearts

作者：King J H; Zhang Y; Lei M; Grace A A; Huang C L H; Fraser J A^*

来源：Acta Physiologica, 2013, 207(2): 308-323.

DOI：10.1111/apha.12006

• atrial fibrillation
• calcium
• conduction velocity
• RyR2
• triggered activity

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 (RyR2S/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 RyR2S/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 RyR2S/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 RyR2S/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 RyR2S/S and WT. Conclusions These results suggest that abnormal intracellular Ca2+ homoeostasis produces both arrhythmic triggers and a slow-conducting arrhythmic substrate in RyR2S/S atria. A similar mechanism might also contribute to arrhythmogenesis in other conditions, associated with diastolic Ca2+release, such as atrial fibrillation.

• 出版日期2013-2