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Sarcoplasmic reticulum Ca2+ leak in heart failure: mere observation or functional relevance?

George, Christopher H 2007. Sarcoplasmic reticulum Ca2+ leak in heart failure: mere observation or functional relevance? Cardiovascular Research 77 (2) , pp. 302-314. 10.1093/cvr/cvm006

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Heart failure (HF) is a chronic multi-factorial disease characterized by sarcoplasmic reticulum (SR) dysfunction that manifests as severely reduced contractility and increased risk of arrhythmia. Several lines of evidence have revealed the existence of defective ryanodine receptor (RyR2)-mediated Ca2+ leak in HF, although its relevance as a causative factor rather than a phenotypic consequence of the disease is questioned. This review will consider the relative contribution of RyR2-mediated Ca2+ leak to the profound cellular, transcriptional and electrical remodelling associated with HF. In particular, it will focus on our current understanding of the role of defective phosphorylation of RyR2 as a both a chronic mediator of excitation–contraction coupling (ECC) dysfunction and as a potent catalyst of RyR2-dependent arrhythmogenesis. A hypothetical concept that SR Ca2+ leak fundamentally underlies the increased arrhythmogenic susceptibility in HF, but that it may not directly contribute to contractile dysfunction, which may involve maladaptive perturbations in metabolism and energy utilization, is also discussed.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: Sarcoplasmic reticulum; Ryanodine receptor; Calcium handling Arrhythmia
Publisher: Elsevier
ISSN: 0008-6363
Last Modified: 28 Jun 2019 02:45

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