Acute atrial arrhythmogenicity and altered Ca2+ homeostasis in murine RyR2-P2328S hearts

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Acute atrial arrhythmogenicity and altered Ca2+ homeostasis in murine RyR2-P2328S hearts

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 assoc...

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Abnormal Ca2+ homeostasis, atrial arrhythmogenesis, and sinus node dysfunction in murine hearts modeling RyR2 modification

Ryanodine receptor type 2 (RyR2) mutations are implicated in catecholaminergic polymorphic ventricular tachycardia (CPVT) thought to result from altered myocyte Ca(2+) homeostasis reflecting inappropriate "leakiness" of RyR2-Ca(2+) release channels arising from increases in their basal activity, alterations in their phosphorylation, or defective interactions with other molecules or ions. The la...

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Flecainide exerts paradoxical effects on sodium currents and atrial arrhythmia in murine RyR2-P2328S hearts

AIMS Cardiac ryanodine receptor mutations are associated with catecholaminergic polymorphic ventricular tachycardia (CPVT), and some, including RyR2-P2328S, also predispose to atrial fibrillation. Recent work associates reduced atrial Nav 1.5 currents in homozygous RyR2-P2328S (RyR2(S/S) ) mice with slowed conduction and increased arrhythmogenicity. Yet clinically, and in murine models, the Nav...

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Pharmacological changes in cellular Ca2+ homeostasis parallel initiation of atrial arrhythmogenesis in murine langendorff-perfused hearts

1. Intracellular Ca(2+) overload has been associated with established atrial arrhythmogenesis. The present experiments went on to correlate acute initiation of atrial arrhythmogenesis in Langendorff-perfused mouse hearts with changes in Ca(2+) homeostasis in isolated atrial myocytes following pharmacological procedures that modified the storage or release of sarcoplasmic reticular (SR) Ca(2+) o...

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Physiological consequences of the P2328S mutation in the ryanodine receptor (RyR2) gene in genetically modified murine hearts

AIM To explore the physiological consequences of the ryanodine receptor (RyR2)-P2328S mutation associated with catecholaminergic polymorphic ventricular tachycardia (CPVT). METHODS We generated heterozygotic (RyR2 p/s) and homozygotic (RyR2 s/s) transgenic mice and studied Ca2+ signals from regularly stimulated, Fluo-3-loaded, cardiac myocytes. Results were compared with monophasic action pot...

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ژورنال

عنوان ژورنال: Cardiovascular Research

سال: 2010

ISSN: 1755-3245,0008-6363

DOI: 10.1093/cvr/cvq229