title: Physiological and pathological modulation of ryanodine receptor function in cardiac muscle.
abstract: Calcium release from the sarcoplasmic reticulum (SR) in cardiac muscle occurs through a specialised release channel, the ryanodine receptor, RyR, via the process of Ca-induced Ca release (CICR). The open probability of the RyR is increased by elevation of cytoplasmic Ca concentration ([Ca(2+)](i)). However, in addition to Ca, other modulators affect the RyR open probability. Agents which increase the RyR opening during systole produce a transient increase of systolic [Ca(2+)](i) followed by a return to the initial level due to a compensating decrease of SR Ca content. Increasing RyR opening during diastole decreases SR Ca content and thereby decreases systolic [Ca(2+)](i). We therefore conclude that potentiation of RyR opening will, if anything, decrease systolic [Ca(2+)](i). The effects of specific examples of modulators of the RyR, such as phosphorylation, metabolic changes, heart failure and polyunsaturated fatty acids, are discussed.
authors.affiliation: Unit of Cardiac Physiology, University of Manchester, 1.524 Stopford Building, Oxford Road, Manchester M13 9PT, UK. eisner@man.ac.uk
authors.forename: D A
authors.initials: DA
authors.lastname: Eisner
authors.forename: M E
authors.initials: ME
authors.lastname: Díaz
authors.forename: S C
authors.initials: SC
authors.lastname: O'Neill
authors.forename: A W
authors.initials: AW
authors.lastname: Trafford
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D006321:Heart / Q000502:physiology*; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium