title: Regulation of sarcoplasmic reticulum Ca2+release by serine-threonine phosphatases in the heart.
abstract: The amount and timing of Ca2+release from the sarcoplasmic reticulum (SR) during cardiac cycle are the main determinants of cardiac contractility. Reversible phosphorylation of the SR Ca2+release channel, ryanodine receptor type 2 (RyR2) is the central mechanism of regulation of Ca2+release in cardiomyocytes. Three major serine-threonine phosphatases including PP1, PP2A and PP2B (calcineurin) have been implicated in modulation of RyR2 function. Changes in expression levels of these phosphatases, their activity and targeting to the RyR2 macromolecular complex were demonstrated in many animal models of cardiac disease and humans and are implicated in cardiac arrhythmia and heart failure. Here we review evidence in support of regulation of RyR2-mediated SR Ca2+release by serine-threonine phosphatases and the role and mechanisms of dysregulation of phosphatases in various disease states.
authors: The Warren Alpert Medical School of Brown University, Rhode Island Hospital, Department of Medicine, Cardiovascular Research Center, United States. Electronic address: dmitry_terentyev@brown.edu.
authors: Dmitry
authors: D
authors: Terentyev
authors: Cardiff University, School of Medicine, Wales Heart Research Institute, United Kingdom.
authors: Shanna
authors: S
authors: Hamilton
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D055786:Gene Knockout Techniques; D006331:Heart Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D009206:Myocardium / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D010749:Phosphoprotein Phosphatases; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium
keywords: Cardiac arrhythmia; Heart failure; Ryanodine receptor; Sarcoplasmic reticulum calcium release; Serine threonine phosphatase