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Atrial arrhythmia, triggering events and conduction abnormalities in isolated murine R y R 2‐ P 2328 S hearts
Author(s) -
King J. H.,
Zhang Y.,
Lei M.,
Grace A. A.,
Huang C. L.H.,
Fraser J. A.
Publication year - 2013
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12006
Subject(s) - ryanodine receptor 2 , medicine , atrial fibrillation , cardiology , nerve conduction velocity , refractory period , afterdepolarization , tachycardia , electrophysiology , ryanodine receptor , chemistry , repolarization , calcium
Aim R y R 2 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 R y R 2‐ P 2328 S ( R y R 2 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 R y R 2 S/S and wild type ( WT ) hearts, perfused using a novel modified L angendorff 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 R y R 2 S/S showed frequent sustained tachyarrhythmias, delayed afterdepolarizations and ectopic AP s, increased interatrial conduction delays, reduced epicardial CV s and reduced maximum rates of AP depolarization ((d V /d t ) max ), despite similar effective refractory periods, AP durations and AP amplitudes. Effective interatrial CV s and (d V /d t ) max values of AP s following ectopic ( S 2) stimulation were lower than those of AP s following regular stimulation and decreased with shortening S 1 S 2 intervals. However, although R y R 2 S/S atria showed arrhythmias over a wider range of S 1 S 2 intervals, the interatrial CV and (d V /d t ) max of S 2 AP s provoking such arrhythmias were similar in R y R 2 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 R y R 2 S/S atria. A similar mechanism might also contribute to arrhythmogenesis in other conditions, associated with diastolic Ca 2+ release, such as atrial fibrillation.