Cardiac sarcoplasmic reticulum calcium leak: basis and roles in cardiac dysfunction

Synchronized SR calcium (Ca) release is critical to normal cardiac myocyte excitation-contraction coupling, and ideally this release shuts off completely between heartbeats. However, other SR Ca release events are referred to collectively as SR Ca leak (which includes Ca sparks and waves as well as...

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Bibliographic Details
Published inAnnual review of physiology Vol. 76; p. 107
Main Author Bers, Donald M
Format Journal Article
LanguageEnglish
Published United States 01.01.2014
Subjects
Animals
Calcium - metabolism
Calcium Signaling - physiology
Heart Diseases - metabolism
Heart Diseases - physiopathology
Humans
Myocardium - metabolism
Myocytes, Cardiac - metabolism
Rabbits
Rats
Ryanodine Receptor Calcium Release Channel - physiology
Sarcoplasmic Reticulum - metabolism
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Summary:Synchronized SR calcium (Ca) release is critical to normal cardiac myocyte excitation-contraction coupling, and ideally this release shuts off completely between heartbeats. However, other SR Ca release events are referred to collectively as SR Ca leak (which includes Ca sparks and waves as well as smaller events not detectable as Ca sparks). Much, but not all, of the SR Ca leak occurs via ryanodine receptors and can be exacerbated in pathological states such as heart failure. The extent of SR Ca leak is important because it can (a) reduce SR Ca available for release, causing systolic dysfunction; (b) elevate diastolic [Ca]i, contributing to diastolic dysfunction; (c) cause triggered arrhythmias; and (d) be energetically costly because of extra ATP used to repump Ca. This review addresses quantitative aspects and manifestations of SR Ca leak and its measurement, and how leak is modulated by Ca, associated proteins, and posttranslational modifications in health and disease.
ISSN:1545-1585
DOI:10.1146/annurev-physiol-020911-153308