Striated muscle regulation of isometric tension by multiple equilibria
| Autor: | Nguyen Van Minh, Javier E. Hasbun, Henry G. Zot |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Biophysics/Theory and Simulation
Myofilament Myosin light-chain kinase Biophysics lcsh:Medicine macromolecular substances Myosins 010402 general chemistry Models Biological Biochemistry 01 natural sciences Fluorescence Physiology/Muscle and Connective Tissue 03 medical and health sciences Myosin head Biophysics/Macromolecular Assemblies and Machines Isometric Contraction Cell Biology/Cytoskeleton Myosin Animals lcsh:Science Biochemistry/Biomacromolecule-Ligand Interactions 030304 developmental biology Oxadiazoles 0303 health sciences Computational Biology/Systems Biology Multidisciplinary Meromyosin Chemistry lcsh:R Computational Biology Tropomyosin Muscle Striated 0104 chemical sciences Muscle Tonus Myosin binding Calcium Biophysics/Biomacromolecule-Ligand Interactions lcsh:Q Myofibril Protein Binding Research Article |
| Zdroj: | PLoS ONE, Vol 4, Iss 12, p e8052 (2009) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Cooperative activation of striated muscle by calcium is based on the movement of tropomyosin described by the steric blocking theory of muscle contraction. Presently, the Hill model stands alone in reproducing both myosin binding data and a sigmoidal-shaped curve characteristic of calcium activation (Hill TL (1983) Two elementary models for the regulation of skeletal muscle contraction by calcium. Biophys J 44: 383-396.). However, the free myosin is assumed to be fixed by the muscle lattice and the cooperative mechanism is based on calcium-dependent interactions between nearest neighbor tropomyosin subunits, which has yet to be validated. As a result, no comprehensive model has been shown capable of fitting actual tension data from striated muscle. We show how variable free myosin is a selective advantage for activating the muscle and describe a mechanism by which a conformational change in tropomyosin propagates free myosin given constant total myosin. This mechanism requires actin, tropomyosin, and filamentous myosin but is independent of troponin. Hence, it will work equally well with striated, smooth and non-muscle contractile systems. Results of simulations with and without data are consistent with a strand of tropomyosin composed of approximately 20 subunits being moved by the concerted action of 3-5 myosin heads, which compares favorably with the predicted length of tropomyosin in the overlap region of thick and thin filaments. We demonstrate that our model fits both equilibrium myosin binding data and steady-state calcium-dependent tension data and show how both the steepness of the response and the sensitivity to calcium can be regulated by the actin-troponin interaction. The model simulates non-cooperative calcium binding both in the presence and absence of strong binding myosin as has been observed. Thus, a comprehensive model based on three well-described interactions with actin, namely, actin-troponin, actin-tropomyosin, and actin-myosin can explain the cooperative calcium activation of striated muscle. |
| Databáze: | OpenAIRE |
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