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.
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.
Authors: Na Li; David Y Chiang; Sufen Wang; Qiongling Wang; Liang Sun; Niels Voigt; Jonathan L Respress; Sameer Ather; Darlene G Skapura; Valerie K Jordan; Frank T Horrigan; Wilhelm Schmitz; Frank U Müller; Miguel Valderrabano; Stanley Nattel; Dobromir Dobrev; Xander H T Wehrens Journal: Circulation Date: 2014-01-07 Impact factor: 29.690
Authors: Qing Lou; Andriy E Belevych; Przemysław B Radwański; Bin Liu; Anuradha Kalyanasundaram; Bjorn C Knollmann; Vadim V Fedorov; Sándor Györke Journal: J Physiol Date: 2014-12-02 Impact factor: 5.182
Authors: Na Li; Qiongling Wang; Martha Sibrian-Vazquez; Robert C Klipp; Julia O Reynolds; Tarah A Word; Larry Scott; Guy Salama; Robert M Strongin; Jonathan J Abramson; Xander H T Wehrens Journal: Int J Cardiol Date: 2016-10-29 Impact factor: 4.164
Authors: Alexey V Glukhov; Anuradha Kalyanasundaram; Qing Lou; Lori T Hage; Brian J Hansen; Andriy E Belevych; Peter J Mohler; Björn C Knollmann; Muthu Periasamy; Sandor Györke; Vadim V Fedorov Journal: Eur Heart J Date: 2013-11-11 Impact factor: 29.983