Abstract |
The RyR ( ryanodine receptor) mediates rapid Ca2+ efflux from the ER (endoplasmic reticulum) and is responsible for triggering numerous Ca2+-activated physiological processes. The most studied RyR-mediated process is excitation-contraction coupling in striated muscle, where plasma membrane excitation is transmitted to the cell interior and results in Ca2+ efflux that triggers myocyte contraction. Recently, single-residue mutations in the cardiac RyR ( RyR2) have been identified in families that exhibit CPVT ( catecholaminergic polymorphic ventricular tachycardia), a condition in which physical or emotional stress can trigger severe tachyarrhythmias that can lead to sudden cardiac death. The RyR2 mutations in CPVT are clustered in the N- and C-terminal domains, as well as in a central domain. Further, a critical signalling role for dysfunctional RyR2 has also been implicated in the generation of arrhythmias in the common condition of HF ( heart failure). We have prepared cardiac RyR2 plasmids with various CPVT mutations to enable expression and analysis of Ca2+ release mediated by the wild-type and mutated RyR2. These studies suggest that the mutational locus may be important in the mechanism of Ca2+ channel dysfunction. Understanding the causes of aberrant Ca2+ release via RyR2 may assist in the development of effective treatments for the ventricular arrhythmias that often leads to sudden death in HF and in CPVT.
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Authors | N L Thomas, C H George, F A Lai |
Journal | Biochemical Society transactions
(Biochem Soc Trans)
Vol. 34
Issue Pt 5
Pg. 913-8
(Nov 2006)
ISSN: 0300-5127 [Print] England |
PMID | 17052226
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Ryanodine Receptor Calcium Release Channel
- Calcium
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Topics |
- Calcium
(metabolism)
- Endoplasmic Reticulum
(physiology)
- Humans
- Models, Molecular
- Mutation
- Myocardium
(pathology)
- Protein Conformation
- Ryanodine Receptor Calcium Release Channel
(chemistry, genetics, physiology)
- Tachycardia, Ventricular
(genetics, physiopathology)
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