striated muscle regulation of isometric tension by multiple equilibria横纹肌等长张力由多个调节平衡.pdfVIP

Striated Muscle Regulation of Isometric Tension by Multiple Equilibria 1 2 3 Henry G. Zot *, Javier E. Hasbun , Nguyen Van Minh 1 Department of Biology, University of West Georgia, Carrollton, Georgia, United States of America, 2 Department of Physics, University of West Georgia, Carrollton, Georgia, United States of America, 3 Department of Mathematics, University of West Georgia, Carrollton, Georgia, United States of America Abstract 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 ,20 subunits being moved by the concerted action of 3–5 myosin heads, which compares favorably with