title: Atrial arrhythmia, triggering events and conduction abnormalities in isolated murine RyR2-P2328S hearts.
abstract: OBJECTIVE
  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.
authors.affiliation: Physiological Laboratory, University of Cambridge, Cambridge, UK.
authors.forename: J H
authors.initials: JH
authors.lastname: King
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: M
authors.initials: M
authors.lastname: Lei
authors.forename: A A
authors.initials: AA
authors.lastname: Grace
authors.forename: C L-H
authors.initials: CL
authors.lastname: Huang
authors.forename: J A
authors.initials: JA
authors.lastname: Fraser
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism*; D004562:Electrocardiography; D006325:Heart Atria / Q000378:metabolism / Q000503:physiopathology*; D051379:Mice; D008817:Mice, Mutant Strains; D009924:Organ Culture Techniques; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics / Q000378:metabolism*
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium