Atrial arrhythmia, triggering events and conduction abnormalities in isolated murine RyR2‐P2328S hearts. (4th October 2012)

• Record Type: Journal Article
• Authors: King, J. H.; Zhang, Y.; Lei, M.; Grace, A. A.; Huang, C. L.‐H.; Fraser, J. A.
• Is Part Of: Acta physiologica. Volume 207:Number 2(2013:Feb.)
• Page Start: 308
• Page End: 323
• Publication Date: 2012-10-04
• Subjects: Physiology -- Periodicals; Physiology -- Research -- Periodicals; 612
• DOI: 10.1111/apha.12006
• Languages: English
• ISSNs: 1748-1708

Abstract

<abstract abstract-type="main" xml:lang="en" id="apha12006-abs-0001"> <title>Abstract</title> <sec id="apha12006-sec-0001" sec-type="section"> <title>Aim</title> <p> <italic>RyR2</italic> 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 <italic>RyR2‐P2328S</italic> (<italic>RyR2</italic><sup>S/S</sup>) hearts for ectopic triggering events and for conduction abnormalities that might provide a re‐entrant substrate.</p> </sec> <sec id="apha12006-sec-0002" sec-type="section"> <title>Methods</title> <p>Electrocardiograph recordings were made from regularly stimulated <italic>RyR2</italic><sup>S/S</sup> 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).</p> </sec> <sec id="apha12006-sec-0003" sec-type="section"> <title>Results</title> <p> <italic>RyR2</italic> <sup>S/S</sup> showed frequent sustained tachyarrhythmias, delayed afterdepolarizations and ectopic APs, increased interatrial conduction delays, reduced epicardial CVs and reduced maximum rates of AP depolarization ((d<italic>V</italic>/d<italic>t</italic>)<sub>max</sub>), despite similar effective refractory periods, AP durations and AP amplitudes. Effective interatrial CVs and (d<italic>V</italic>/d<italic>t</italic>)<sub>max</sub> values of APs following ectopic (S2) stimulation were lower than those of APs following regular stimulation and decreased with shortening S1S2 intervals. However, although <italic>RyR2</italic><sup><italic>S/S</italic></sup> atria showed arrhythmias over a wider range of S1S2 intervals, the interatrial CV and (d<italic>V</italic>/d<italic>t</italic>)<sub>max</sub> of S2 APs provoking such arrhythmias were similar in <italic>RyR2</italic><sup><italic>S/S</italic></sup> and WT.</p> </sec> <sec id="apha12006-sec-0004" sec-type="section"> <title>Conclusions</title> <p>These results suggest that abnormal intracellular Ca<sup>2+</sup> homoeostasis produces both arrhythmic triggers and a slow‐conducting arrhythmic substrate in <italic>RyR2</italic><sup>S/S</sup> atria. A similar mechanism might also contribute to arrhythmogenesis in other conditions, associated with diastolic Ca<sup>2+</sup>release, such as atrial fibrillation.</p> </sec> </abstract>