Is ryanodine receptor phosphorylation key to the fight or flight response and heart failure?

In situations of stress the heart beats faster and stronger. According to Marks and colleagues, this response is, to a large extent, the consequence of facilitated Ca²+ release from intracellular Ca²+ stores via ryanodine receptor 2 (RyR2), thought to be due to catecholamine-induced increases in RyR...

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Bibliographic Details
Published inThe Journal of clinical investigation Vol. 120; no. 12; pp. 4197 - 4203
Main Author Eschenhagen, Thomas
Format Journal Article
LanguageEnglish
Published United States American Society for Clinical Investigation 01.12.2010
Subjects
Alarm reaction
Animals
Arrhythmia
Biomedical research
Calcium - metabolism
Care and treatment
Cell receptors
Excitation Contraction Coupling
Heart failure
Heart Failure - etiology
Heart Failure - genetics
Heart Failure - metabolism
Humans
Mice
Mice, Mutant Strains
Models, Cardiovascular
Myocardium - metabolism
Observations
Phosphorylation
Physiological aspects
Properties
Ryanodine Receptor Calcium Release Channel - chemistry
Ryanodine Receptor Calcium Release Channel - genetics
Ryanodine Receptor Calcium Release Channel - metabolism
Serine - chemistry
Stress, Physiological
United States
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Summary:In situations of stress the heart beats faster and stronger. According to Marks and colleagues, this response is, to a large extent, the consequence of facilitated Ca²+ release from intracellular Ca²+ stores via ryanodine receptor 2 (RyR2), thought to be due to catecholamine-induced increases in RyR2 phosphorylation at serine 2808 (S2808). If catecholamine stimulation is sustained (for example, as occurs in heart failure), RyR2 becomes hyperphosphorylated and "leaky," leading to arrhythmias and other pathology. This "leaky RyR2 hypothesis" is highly controversial. In this issue of the JCI, Marks and colleagues report on two new mouse lines with mutations in S2808 that provide strong evidence supporting their theory. Moreover, the experiments revealed an influence of redox modifications of RyR2 that may account for some discrepancies in the field.
ISSN:0021-9738
1558-8238
DOI:10.1172/jci45251