In cardiac muscle, release of activator calcium from the sarcoplasmic reticulum occurs by calcium- induced calcium release through ryanodine receptors (RyRs), which are clustered in a dense, regular, two-dimensional lattice array at the diad junction. We simulated numerically the stochastic dynamics of RyRs and L-type sarcolemmal calcium channels interacting via calcium nano-domains in the junctional cleft. Four putative RyR gating schemes based on single-channel measurements in lipid bilayers all failed to give stable excitation–contraction coupling, due either to insufficiently strong inactivation to terminate locally regenerative calcium-induced calcium release or insufficient cooperativity to discriminate against RyR activation by background calcium. If the ryanodine receptor was represented, instead, by a phenomenological four-state gating scheme, with channel opening resulting from simultaneous binding of two Ca2+ ions, and either calcium-dependent or activation-linked inactivation, the simulations gave a good semiquantitative accounting for the macroscopic features of excitation–contraction coupling. It was possible to restore stability to a model based on a bilayer-derived gating scheme, by introducing allosteric interactions between nearest-neighbor RyRs so as to stabilize the inactivated state and produce cooperativity among calcium binding sites on different RyRs. Such allosteric coupling between RyRs may be a function of the foot process and lattice array, explaining their conservation during evolution.
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1 March 1999
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March 01 1999
Local Control Models of Cardiac Excitation–Contraction Coupling : A Possible Role for Allosteric Interactions between Ryanodine Receptors
Michael D. Stern,
Michael D. Stern
From the *Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224; ‡Division of Pulmonary and Critical Care Medicine, Johns Hopkins Medical Institutes, Baltimore, Maryland 21224; and §Molecular Biophysics and Physiology, Rush University School of Medicine, Chicago, Illinois 60612
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Long-Sheng Song,
Long-Sheng Song
From the *Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224; ‡Division of Pulmonary and Critical Care Medicine, Johns Hopkins Medical Institutes, Baltimore, Maryland 21224; and §Molecular Biophysics and Physiology, Rush University School of Medicine, Chicago, Illinois 60612
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Heping Cheng,
Heping Cheng
From the *Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224; ‡Division of Pulmonary and Critical Care Medicine, Johns Hopkins Medical Institutes, Baltimore, Maryland 21224; and §Molecular Biophysics and Physiology, Rush University School of Medicine, Chicago, Illinois 60612
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James S.K. Sham,
James S.K. Sham
From the *Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224; ‡Division of Pulmonary and Critical Care Medicine, Johns Hopkins Medical Institutes, Baltimore, Maryland 21224; and §Molecular Biophysics and Physiology, Rush University School of Medicine, Chicago, Illinois 60612
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Huang Tian Yang,
Huang Tian Yang
From the *Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224; ‡Division of Pulmonary and Critical Care Medicine, Johns Hopkins Medical Institutes, Baltimore, Maryland 21224; and §Molecular Biophysics and Physiology, Rush University School of Medicine, Chicago, Illinois 60612
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Kenneth R. Boheler,
Kenneth R. Boheler
From the *Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224; ‡Division of Pulmonary and Critical Care Medicine, Johns Hopkins Medical Institutes, Baltimore, Maryland 21224; and §Molecular Biophysics and Physiology, Rush University School of Medicine, Chicago, Illinois 60612
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Eduardo Ríos
Eduardo Ríos
From the *Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224; ‡Division of Pulmonary and Critical Care Medicine, Johns Hopkins Medical Institutes, Baltimore, Maryland 21224; and §Molecular Biophysics and Physiology, Rush University School of Medicine, Chicago, Illinois 60612
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Michael D. Stern
From the *Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224; ‡Division of Pulmonary and Critical Care Medicine, Johns Hopkins Medical Institutes, Baltimore, Maryland 21224; and §Molecular Biophysics and Physiology, Rush University School of Medicine, Chicago, Illinois 60612
Long-Sheng Song
From the *Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224; ‡Division of Pulmonary and Critical Care Medicine, Johns Hopkins Medical Institutes, Baltimore, Maryland 21224; and §Molecular Biophysics and Physiology, Rush University School of Medicine, Chicago, Illinois 60612
Heping Cheng
From the *Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224; ‡Division of Pulmonary and Critical Care Medicine, Johns Hopkins Medical Institutes, Baltimore, Maryland 21224; and §Molecular Biophysics and Physiology, Rush University School of Medicine, Chicago, Illinois 60612
James S.K. Sham
From the *Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224; ‡Division of Pulmonary and Critical Care Medicine, Johns Hopkins Medical Institutes, Baltimore, Maryland 21224; and §Molecular Biophysics and Physiology, Rush University School of Medicine, Chicago, Illinois 60612
Huang Tian Yang
From the *Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224; ‡Division of Pulmonary and Critical Care Medicine, Johns Hopkins Medical Institutes, Baltimore, Maryland 21224; and §Molecular Biophysics and Physiology, Rush University School of Medicine, Chicago, Illinois 60612
Kenneth R. Boheler
From the *Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224; ‡Division of Pulmonary and Critical Care Medicine, Johns Hopkins Medical Institutes, Baltimore, Maryland 21224; and §Molecular Biophysics and Physiology, Rush University School of Medicine, Chicago, Illinois 60612
Eduardo Ríos
From the *Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224; ‡Division of Pulmonary and Critical Care Medicine, Johns Hopkins Medical Institutes, Baltimore, Maryland 21224; and §Molecular Biophysics and Physiology, Rush University School of Medicine, Chicago, Illinois 60612
Address correspondence to Michael D. Stern, Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224. Fax: 410-558-8150; E-mail: [email protected] or [email protected]
Received:
October 20 1998
Accepted:
January 20 1999
Online ISSN: 1540-7748
Print ISSN: 0022-1295
1999
J Gen Physiol (1999) 113 (3): 469–489.
Article history
Received:
October 20 1998
Accepted:
January 20 1999
Citation
Michael D. Stern, Long-Sheng Song, Heping Cheng, James S.K. Sham, Huang Tian Yang, Kenneth R. Boheler, Eduardo Ríos; Local Control Models of Cardiac Excitation–Contraction Coupling : A Possible Role for Allosteric Interactions between Ryanodine Receptors. J Gen Physiol 1 March 1999; 113 (3): 469–489. doi: https://doi.org/10.1085/jgp.113.3.469
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