Regulation of sarcoplasmic reticulum Ca2+ release by serine-threonine phosphatases in the heart

Terentyev, Dmitry and Hamilton, Shanna 2016. Regulation of sarcoplasmic reticulum Ca2+ release by serine-threonine phosphatases in the heart. Journal of Molecular and Cellular Cardiology 101 , pp. 156-164. 10.1016/j.yjmcc.2016.08.020

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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.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine
Publisher:	Elsevier
ISSN:	0022-2828
Date of Acceptance:	27 August 2016
Last Modified:	11 Dec 2020 03:19
URI:	https://orca.cardiff.ac.uk/id/eprint/103369

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