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Science 31 March 1995:
Vol. 267. no. 5206, pp. 1997 - 2000
DOI: 10.1126/science.7701323
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Articles

Science, Vol 267, Issue 5206, 1997-2000
Copyright © 1995 by American Association for the Advancement of Science

articles

Rapid adaptation of cardiac ryanodine receptors: modulation by Mg2+ and phosphorylation

HH Valdivia, JH Kaplan, GC Ellis-Davies, and WJ Lederer

Department of Physiology, University of Maryland Medical School, Baltimore 21201, USA.

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.


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Impaired cardiomyocyte relaxation and diastolic function in transgenic mice expressing slow skeletal troponin I in the heart.
R. C Fentzke, S. H Buck, J. R Patel, H. Lin, B. M Wolska, M. O Stojanovic, A. F Martin, R J. Solaro, R. L Moss, and J. M Leiden (1999)
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Ca channels in cardiac myocytes: structure and function in Ca influx and intracellular Ca release.
D. M Bers and E. Perez-Reyes (1999)
Cardiovasc Res 42, 339-360
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Local Control Models of Cardiac Excitation-Contraction Coupling: A Possible Role for Allosteric Interactions between Ryanodine Receptors.
M. D. Stern, L.-S. Song, H. Cheng, J. S.K. Sham, H. T. Yang, K. R. Boheler, and E. Rios (1999)
J. Gen. Physiol. 113, 469-489
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Bay K 8644 Increases Resting Ca2+ Spark Frequency in Ferret Ventricular Myocytes Independent of Ca Influx : Contrast With Caffeine and Ryanodine Effects.
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J. S. K. Sham, L.-S. Song, Y. Chen, L.-H. Deng, M. D. Stern, E. G. Lakatta, and H. Cheng (1998)
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J. Physiol. 510, 155-164
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The control of Ca release from the cardiac sarcoplasmic reticulum: regulation versus autoregulation.
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Voltage change-induced gating transitions of the rabbit skeletal muscle Ca2+ release channel.
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Endocrinology 138, 2056-2065
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Ca2+-induced Ca2+ Release in Chinese Hamster Ovary (CHO) Cells Co-expressing Dihydropyridine and Ryanodine Receptors.
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Peptide Probe of Ryanodine Receptor Function.
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