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Acute atrial arrhythmogenicity and altered Ca(2+) homeostasis in murine RyR2-P2328S hearts.

Zhang, Y, Fraser, JA, Jeevaratnam, K, Hao, X, Hothi, SS, Grace, AA, Lei, M and Huang, CL (2011) Acute atrial arrhythmogenicity and altered Ca(2+) homeostasis in murine RyR2-P2328S hearts. Cardiovasc Res, 89 (4). pp. 794-804.

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Abstract

AIMS: The experiments explored for atrial arrhythmogenesis and its possible physiological background in recently developed hetero-(RyR2(+/S)) and homozygotic (RyR2(S/S)) RyR2-P2328S murine models for catecholaminergic polymorphic ventricular tachycardia (VT) for the first time. They complement previous clinical and experimental reports describing increased ventricular arrhythmic tendencies associated with physical activity, stress, or catecholamine infusion, potentially leading to VT and ventricular fibrillation. METHODS AND RESULTS: Atrial arrhythmogenic properties were compared at the whole animal, Langendorff-perfused heart, and single, isolated atrial myocyte levels using electrophysiological and confocal fluorescence microscopy methods. This demonstrated that: (i) electrocardiographic parameters in intact anaesthetized wild-type (WT), RyR2(+/S) and RyR2(S/S) mice were statistically indistinguishable both before and after addition of isoproterenol apart from increases in heart rates. (ii) Bipolar electrogram and monophasic action potential recordings showed significantly higher incidences of arrhythmogenesis in isolated perfused RyR2(S/S), but not RyR2(+/S), relative to WT hearts during either regular pacing or programmed electrical stimulation. The addition of isoproterenol increased such incidences in all three groups. (iii) However, there were no accompanying differences in cardiac anatomy or action potential durations at 90% repolarization and refractory periods. (iv) In contrast, episodes of diastolic Ca(2+) release were observed under confocal microscopy in isolated fluo-3-loaded RyR2(S/S), but not RyR2(+/S) or WT, atrial myocytes. The introduction of isoproterenol resulted in significant diastolic Ca(2+) release in all three groups. CONCLUSIONS: These findings establish acute atrial arrhythmogenic properties in RyR2-P2328S hearts and correlate these with altered Ca(2+) homeostasis in an absence of repolarization abnormalities for the first time.

Item Type: Article
Authors :
NameEmailORCID
Zhang, YUNSPECIFIEDUNSPECIFIED
Fraser, JAUNSPECIFIEDUNSPECIFIED
Jeevaratnam, Kk.jeevaratnam@surrey.ac.ukUNSPECIFIED
Hao, XUNSPECIFIEDUNSPECIFIED
Hothi, SSUNSPECIFIEDUNSPECIFIED
Grace, AAUNSPECIFIEDUNSPECIFIED
Lei, MUNSPECIFIEDUNSPECIFIED
Huang, CLUNSPECIFIEDUNSPECIFIED
Date : 1 March 2011
Identification Number : 10.1093/cvr/cvq229
Uncontrolled Keywords : Action Potentials, Acute Disease, Animals, Calcium, Electrocardiography, Homeostasis, Mice, Mutation, Myocardium, Refractory Period, Electrophysiological, Ryanodine Receptor Calcium Release Channel, Ventricular Fibrillation
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 10:27
Last Modified : 17 May 2017 14:49
URI: http://epubs.surrey.ac.uk/id/eprint/827847

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