Local Control Models of Cardiac Excitation–Contraction Coupling: A Possible Role for Allosteric Interactions between Ryanodine Receptors

Michael D Stern; Long-Sheng Song; Heping Cheng; James S.K Sham; Huang Tian Yang; Kenneth R Boheler; Eduardo Ríos

doi:10.1085/jgp.113.3.469

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Local Control Models of Cardiac Excitation–Contraction Coupling: A Possible Role for Allosteric Interactions between Ryanodine Receptors

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Local Control Models of Cardiac Excitation–Contraction Coupling: A Possible Role for Allosteric Interactions between Ryanodine Receptors

Michael D Stern, Long-Sheng Song, Heping Cheng, James S.K Sham, Huang Tian Yang, Kenneth R Boheler and Eduardo Ríos

The Journal of general physiology, Vol.113(3), pp.469-489

03/01/1999

DOI: 10.1085/jgp.113.3.469

PMID: 10051521

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Abstract

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 Ca 2+ 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.

diad junction

Monte Carlo

sarcoplasmic reticulum

calcium-induced calcium release

dihydropyridine receptor

Details

Title: Subtitle: Local Control Models of Cardiac Excitation–Contraction Coupling: A Possible Role for Allosteric Interactions between Ryanodine Receptors
Creators: Michael D Stern - From the
Long-Sheng Song - From the
Heping Cheng - From the
James S.K Sham - From the
Huang Tian Yang - From the
Kenneth R Boheler - From the
Eduardo Ríos - From the
Resource Type: Journal article
Publication Details: The Journal of general physiology, Vol.113(3), pp.469-489
DOI: 10.1085/jgp.113.3.469
PMID: 10051521
NLM abbreviation: J Gen Physiol
ISSN: 0022-1295
eISSN: 1540-7748
Publisher: The Rockefeller University Press
Language: English
Date published: 03/01/1999
Academic Unit: Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Internal Medicine
Record Identifier: 9984094665502771

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