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

Zhang, Yanmin, Matthews, Gareth D.K. ORCID: https://orcid.org/0000-0001-8353-4806, Lei, Ming and Huang, Christopher L.H. (2013) Abnormal Ca2+ homeostasis, atrial arrhythmogenesis, and sinus node dysfunction in murine hearts modeling RyR2 modification. Frontiers in Physiology, 4 JUN. ISSN 1664-042X

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Ryanodine receptor type 2 (RyR2) mutations are implicated in catecholaminergic polymorphic ventricular tachycardia (CPVT) thought to result from altered myocyte Ca2+ homeostasis reflecting inappropriate "leakiness" of RyR2-Ca2+ release channels arising from increases in their basal activity, alterations in their phosphorylation, or defective interactions with other molecules or ions. The latter include calstabin, calsequestrin-2, Mg2+, and extraluminal or intraluminal Ca2+. Recent clinical studies additionally associate RyR2 abnormalities with atrial arrhythmias including atrial tachycardia (AT), fibrillation (AF), and standstill, and sinus node dysfunction (SND). Some RyR2 mutations associated with CPVT in mouse models also show such arrhythmias that similarly correlate with altered Ca2+ homeostasis. Some examples show evidence for increased Ca2+/calmodulin-dependent protein kinase II (CaMKII) phosphorylation of RyR2. A homozygotic RyR2-P2328S variant demonstrates potential arrhythmic substrate resulting from reduced conduction velocity (CV) in addition to delayed afterdepolarizations (DADs) and ectopic action potential (AP) firing. Finally, one model with an increased RyR2 activity in the sino-atrial node (SAN) shows decreased automaticity in the presence of Ca2+-dependent decreases in ICa, L and diastolic sarcoplasmic reticular (SR) Ca2+ depletion.

Item Type: Article
Uncontrolled Keywords: atrial arrhythmias,mouse models,mutation,ryr2,sinus node dysfunction,physiology,physiology (medical) ,/dk/atira/pure/subjectarea/asjc/1300/1314
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 10 Nov 2022 13:30
Last Modified: 15 Dec 2022 03:46
URI: https://ueaeprints.uea.ac.uk/id/eprint/89768
DOI: 10.3389/fphys.2013.00150

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