Physiological and pathological modulation of ryanodine receptor function in cardiac muscle.
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.
Eisner
D A
DA
Unit of Cardiac Physiology, University of Manchester, 1.524 Stopford Building, Oxford Road, Manchester M13 9PT, UK. eisner@man.ac.uk
Díaz
M E
ME
O'Neill
S C
SC
Trafford
A W
AW
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*
D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium