%0 Journal Article %1 Ster_1999_469 %A Stern, M. D. %A Song, L. S. %A Cheng, H. %A Sham, J. S. %A Yang, H. T. %A Boheler, K. R. %A R�os, E. %D 1999 %J J. Gen. Physiol. %K Algorithms; Animals; Biological; Calcium Carlo Channel Channel, Channels, Computer Contraction, Energy Gating, Heart, Ion L-Type; Metabolism, Method; Models, Monte Muscle Myocardial Proteins, Rats; Receptor Release Reticulum, Ryanodine Sarcoplasmic Simulation; metabolism physiology; %N 3 %P 469--489 %T Local control models of cardiac excitation-contraction coupling. A possible role for allosteric interactions between ryanodine receptors. %U http://www.jgp.org/cgi/content/abstract/113/3/469 %V 113 %X 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.

@article{Ster_1999_469, 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 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.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Stern, M. D. and Song, L. S. and Cheng, H. and Sham, J. S. and Yang, H. T. and Boheler, K. R. and R�os, E.}, biburl = {https://www.bibsonomy.org/bibtex/273b5001df51085078782745b8be0ae8c/hake}, description = {The whole bibliography file I use.}, file = {Ster_1999_469.pdf:Ster_1999_469.pdf:PDF}, institution = {Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. sternM@grc.nia.nih.gov}, interhash = {f39f026ca7cee525b90a44033713b7b2}, intrahash = {73b5001df51085078782745b8be0ae8c}, journal = {J. Gen. Physiol.}, keywords = {Algorithms; Animals; Biological; Calcium Carlo Channel Channel, Channels, Computer Contraction, Energy Gating, Heart, Ion L-Type; Metabolism, Method; Models, Monte Muscle Myocardial Proteins, Rats; Receptor Release Reticulum, Ryanodine Sarcoplasmic Simulation; metabolism physiology;}, month = Mar, number = 3, pages = {469--489}, pdf = {Ster_1999_469.pdf}, pmid = {10051521}, timestamp = {2009-06-03T11:21:33.000+0200}, title = {Local control models of cardiac excitation-contraction coupling. A possible role for allosteric interactions between ryanodine receptors.}, url = {http://www.jgp.org/cgi/content/abstract/113/3/469}, volume = 113, year = 1999 }