title: Modulation of cardiac ryanodine receptor activity by ROS and RNS.
abstract: Calcium release through cardiac ryanodine receptors (RyR2) triggers heart muscle contraction. Reactive oxygen/nitrogen species (ROS/RNS), normally produced in the heart, promote endogenous RyR2 S-nitrosylation and S-glutathionylation. These reversible redox modifications increase RyR2 activity in vitro, and presumably also in vivo. RyR2 S-glutathionylation increases under physiologically relevant conditions (tachycardia and exercise), suggesting that cardiac cells utilize this redox modification to increase RyR2 activity under increased demand. In contrast, in vivo changes in RyR2 S-nitrosylation in response to physiological stimuli remain uncharacterized. The number and identity of the highly reactive RyR2 cysteine residues and the nature of the redox modification they undergo are presently unknown. Likewise, the physiological sources of ROS/RNS responsible for functionally relevant RyR2 redox modifications have not been completely identified. The redox state of RyR2 is altered in heart failure leading to enhanced RyR2 activity, which presumably contributes to decrease SR calcium content and induce other calcium release abnormalities observed in heart failure. Greater understanding of RyR2 redox modulation is necessary to counteract the deleterious consequences of RyR2 activity deregulation caused by oxidative stress.
authors.affiliation: Facultad de Medicina, Instituto de Ciencias Biomedicas and Centro de Estudios Moleculares de la Celula, Universidad de Chile, 838-0453 Santiago, Chile. pdonoso@med.uchile.cl
authors.forename: Paulina
authors.initials: P
authors.lastname: Donoso
authors.forename: Gina
authors.initials: G
authors.lastname: Sanchez
authors.forename: Ricardo
authors.initials: R
authors.lastname: Bull
authors.forename: Cecilia
authors.initials: C
authors.lastname: Hidalgo
mesh_terms: D002118:Calcium / Q000378:metabolism; D003545:Cysteine / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006321:Heart / Q000502:physiology; D032383:Myocytes, Cardiac / Q000201:enzymology; D019255:NADPH Oxidases / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010084:Oxidation-Reduction; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
chemical_list: D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D019837:Ryanodine Receptor Calcium Release Channel; D019001:Nitric Oxide Synthase; D019255:NADPH Oxidases; D005978:Glutathione; D003545:Cysteine; D002118:Calcium