Physiological and pathological modulation of ryanodine receptor function in cardiac muscle.

, , , and . Cell Calcium 35 (6): 583--589 (June 2004)


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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