Rapid adaptation of cardiac ryanodine receptors: modulation by Mg2+ 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 (Ca2+) to repeatedly but transiently activate channels. Adaptation of RyRs in the absence of magnesium (Mg2+) and adenosine triphosphate is an extremely slow process (taking seconds). Photorelease of Ca2+ from nitrophenyl-EGTA, a photolabile Ca2+ chelator, demonstrated that RyR adaptation is rapid (milliseconds) in canine heart muscle when physiological Mg2+ concentrations are present. Phosphorylation of the RyR by protein kinase A increased the responsiveness of the channel to Ca2+ 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.
Valdivia
H H
HH
Department of Physiology, University of Maryland Medical School, Baltimore 21201, USA.
Kaplan
J H
JH
Ellis-Davies
G C
GC
Lederer
W J
WJ
D000222:Adaptation, Physiological; D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004285:Dogs; D007700:Kinetics; D008051:Lipid Bilayers; D008274:Magnesium / Q000494:pharmacology*; D009124:Muscle Proteins / Q000187:drug effects / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010766:Phosphorylation; D019837:Ryanodine Receptor Calcium Release Channel
D015220:Calcium Channels; D008051:Lipid Bilayers; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D000255:Adenosine Triphosphate; D017868:Cyclic AMP-Dependent Protein Kinases; D008274:Magnesium; D002118:Calcium