Referenced in: none

Automatically associated channels: Kv10.1

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

Authors: Thomas Eschenhagen

Journal, date & volume: J. Clin. Invest., 2010 Dec 1 , 120, 4197-203

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21099119

Abstract
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.