Physiological and pathological modulation of ryanodine receptor function in cardiac muscle |
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Authors: | Eisner D A Díaz M E O'Neill S C Trafford A W |
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Affiliation: | Unit of Cardiac Physiology, University of Manchester, 1.524 Stopford Building, Oxford Road, Manchester M13 9PT, UK. eisner@man.ac.uk |
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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. |
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Keywords: | Calcium release Ryanodine receptor Cardiac muscle Sarcoplasmic reticulum |
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