title: Is ryanodine receptor phosphorylation key to the fight or flight response and heart failure?
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.
authors.affiliation: Department of Experimental Pharmacology and Toxicology, Cardiovascular Research Center Hamburg, University Medical Center Hamburg Eppendorf, Hamburg, Germany.  t.eschenhagen@uke.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Eschenhagen
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D056966:Excitation Contraction Coupling; D006333:Heart Failure / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D008955:Models, Cardiovascular; D009206:Myocardium / Q000378:metabolism; D010766:Phosphorylation; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000737:chemistry; D013312:Stress, Physiological
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D012694:Serine; D002118:Calcium