Rapid Adaptation of Cardiac Ryanodine Receptors: Modulation by Mg$^{2+}$ and Phosphorylation

Channel adaptation is a fundamental feature of sarcoplasmic reticulum calcium release channels (called ryanodine receptors, RyRs). It permits successive increases in the intracellular concentration of calcium (Ca$^{2+}$) to repeatedly but transiently activate channels. Adaptation of RyRs in the abse...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 1995-03, Vol.267 (5206), p.1997-2000
Main Authors: Valdivia, Hector H., Kaplan, Jack H., Graham C. R. Ellis-Davies, Lederer, W. Jonathan
Format: Article
Language:English
Subjects:
Electrodes
Kinetics
Lasers
Lipid bilayers
Myocardium
Phosphorylation
Receptors
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Summary:Channel adaptation is a fundamental feature of sarcoplasmic reticulum calcium release channels (called ryanodine receptors, RyRs). It permits successive increases in the intracellular concentration of calcium (Ca$^{2+}$) to repeatedly but transiently activate channels. Adaptation of RyRs in the absence of magnesium (Mg$^{2+}$) and adenosine triphosphate is an extremely slow process (taking seconds). Photorelease of Ca$^{2+}$ from nitrophenyl-EGTA, a photolabile Ca$^{2+}$ chelator, demonstrated that RyR adaptation is rapid (milliseconds) in canine heart muscle when physiological Mg$^{2+}$ concentrations are present. Phosphorylation of the RyR by protein kinase A increased the responsiveness of the channel to Ca$^{2+}$ and accelerated the kinetics of adaptation. These properties of the RyR from heart may also be relevant to other cells in which multiple agonist-dependent triggering events regulate cellular functions.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.7701323