Local control models of cardiac excitation-contraction coupling. A possible role for allosteric interactions between ryanodine receptors
| Autor: | M D, Stern, L S, Song, H, Cheng, J S, Sham, H T, Yang, K R, Boheler, E, Ríos |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
diad junction
Calcium Channels L-Type Muscle Proteins Heart Ryanodine Receptor Calcium Release Channel musculoskeletal system Models Biological Myocardial Contraction Article Rats sarcoplasmic reticulum Animals dihydropyridine receptor Computer Simulation Calcium Channels Energy Metabolism Ion Channel Gating Monte Carlo Method Monte Carlo Algorithms calcium-induced calcium release |
| Zdroj: | The Journal of General Physiology |
| ISSN: | 0022-1295 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|