The mechanism of muscle contraction. Biochemical, mechanical, and structural approaches to elucidate cross-bridge action in muscle.

Muscle contraction occurs when the thin actin and thick myosin filaments slide past each other. It is generally assumed that this process is driven by cross-bridges which extend from the myosin filaments and cyclically interact with the actin filaments as ATP is hydrolysed. Current biochemical studies suggest that the myosin cross-bridge exists in two main conformations. In one conformation, which occurs in the absence of MgATP, the cross-bridge binds very tightly to actin and detaches very slowly. When all the cross-bridges are bound in this way, the muscle is in rigor and extremely resistant to stretch. The second conformation is induced by the binding of MgATP. In this conformation the cross-bridge binds weakly to actin and attaches and detaches so rapidly that it can slip from actin site to actin site, offering very little resistance to stretch. During ATP hydrolysis by isolated actin and myosin in solution, the cross-bridge cycles back and forth between the weak-binding and strong-binding conformations. Assuming a close correlation between the behaviour of isolated proteins in solution and the cross-bridge action in muscle, Eisenberg and Greene have developed a model for cross-bridge action where, in the fixed filament lattice in muscle, the transition from the weak-binding to the strong-binding conformation causes the elastic cross-bridge to become deformed and exert a positive force, while the transition back to the weak-binding conformation upon binding of MgATP, causes deformation which, during fibre shortening, leads to rapid detachment of the cross-bridge and its re-attachment to a new actin site. From the results of in vitro experiments, it was furthermore suggested that relaxation occurs when the transition from the weak-binding to the strong-binding conformation is blocked. Results of recent mechanical and X-ray diffraction experiments on skinned fibre preparations are consistent with the assumed close correlation between the behaviour of isolated proteins in solution and the behaviour of cross-bridges in muscle. Furthermore, X-ray diffraction experiments allowed to provide experimental evidence for the postulated structural difference between attached weak-binding and attached strong-binding cross-bridges. Finally, recent studies have confirmed the prediction of Eisenberg and Greene that the rate limiting step in vitro determines the rate of force generation in muscle.

[1]  H E Huxley,et al.  The Mechanism of Muscular Contraction , 1965, Scientific American.

[2]  E. Eisenberg,et al.  The relation of muscle biochemistry to muscle physiology. , 1980, Annual review of physiology.

[3]  Steven B Marston,et al.  Evidence for a complex between myosin and ADP in relaxed muscle fibres. , 1972, Nature: New biology.

[4]  B. Brenner,et al.  High-resolution equatorial x-ray diffraction from single skinned rabbit psoas fibers. , 1986, Biophysical journal.

[5]  K. Holmes,et al.  Induced Changes in Orientation of the Cross-Bridges of Glycerinated Insect Flight Muscle , 1965, Nature.

[6]  Steven B Marston,et al.  The rates of formation and dissociation of actin-myosin complexes. Effects of solvent, temperature, nucleotide binding and head-head interactions. , 1982, The Biochemical journal.

[7]  E. Eisenberg,et al.  Mechanism of the actomyosin ATPase: effect of actin on the ATP hydrolysis step. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[8]  H. Huxley Structural difference between resting and rigor muscle; evidence from intensity changes in the lowangle equatorial x-ray diagram. , 1968, Journal of molecular biology.

[9]  E. Eisenberg,et al.  Mechanism of action of troponin . tropomyosin. Inhibition of actomyosin ATPase activity without inhibition of myosin binding to actin. , 1981, The Journal of biological chemistry.

[10]  B. Brenner,et al.  X-ray diffraction evidence for cross-bridge formation in relaxed muscle fibers at various ionic strengths. , 1984, Biophysical journal.

[11]  E. Eisenberg,et al.  Rate of force generation in muscle: correlation with actomyosin ATPase activity in solution. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[12]  S. Rosenfeld,et al.  The ATPase mechanism of skeletal and smooth muscle acto-subfragment 1. , 1984, The Journal of biological chemistry.

[13]  E. Taylor,et al.  Mechanism of adenosine triphosphate hydrolysis by actomyosin. , 1971, Biochemistry.

[14]  E. Eisenberg,et al.  Evidence for cross-bridge attachment in relaxed muscle at low ionic strength. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[15]  Steven B Marston The nucleotide complexes of myosin in glycerol-extracted muscle fibres. , 1973, Biochimica et biophysica acta.

[16]  D. Moisescu,et al.  Kinetics of reaction in calcium-activated skinned muscle fibres , 1976, Nature.

[17]  B. Brenner Cross bridge attachment during isotonic shortening in single skinned rabbit psoas fibers , 1983 .

[18]  B. Brenner,et al.  The cross-bridge cycle in muscle. Mechanical, biochemical, and structural studies on single skinned rabbit psoas fibers to characterize cross-bridge kinetics in muscle for correlation with the actomyosin-ATPase in solution. , 1986, Basic research in cardiology.

[19]  A. Huxley Muscular contraction. Review lecture , 1974 .

[20]  J. Haselgrove,et al.  X-ray evidence for radial cross-bridge movement and for the sliding filament model in actively contracting skeletal muscle. , 1973, Journal of molecular biology.

[21]  A. Oplatka,et al.  On the formation and stability of the enzymically active complexes of heavy meromyosin with actin. , 1969, Journal of molecular biology.

[22]  M. Schoenberg Equilibrium muscle cross-bridge behavior. Theoretical considerations. , 1985, Biophysical journal.

[23]  H. Huxley,et al.  Changes in the Cross-Striations of Muscle during Contraction and Stretch and their Structural Interpretation , 1954, Nature.

[24]  A. Huxley,et al.  Structural Changes in Muscle During Contraction: Interference Microscopy of Living Muscle Fibres , 1954, Nature.

[25]  E. Eisenberg,et al.  Inhibition of actomyosin ATPase activity by troponin-tropomyosin without blocking the binding of myosin to actin. , 1982, The Journal of biological chemistry.

[26]  D. Mornet,et al.  Structure of the actin–myosin interface , 1981, Nature.

[27]  E. Eisenberg,et al.  Rate-limiting step in the actomyosin adenosinetriphosphatase cycle: studies with myosin subfragment 1 cross-linked to actin. , 1985, Biochemistry.

[28]  E. Eisenberg,et al.  Stiffness of skinned rabbit psoas fibers in MgATP and MgPPi solution. , 1986, Biophysical journal.

[29]  A. Huxley,et al.  Proposed Mechanism of Force Generation in Striated Muscle , 1971, Nature.

[30]  A. Huxley Muscle structure and theories of contraction. , 1957, Progress in biophysics and biophysical chemistry.

[31]  E. Eisenberg,et al.  Cross-bridge attachment in relaxed muscle. , 1984, Advances in experimental medicine and biology.

[32]  E. Taylor,et al.  Energetics and mechanism of actomyosin adenosine triphosphatase. , 1976, Biochemistry.

[33]  Leepo C. Yu,et al.  Equatorial x-ray intensities and isometric force levels in frog sartorius muscle. , 1979, Journal of molecular biology.

[34]  T. L. Hill,et al.  Muscle contraction and free energy transduction in biological systems. , 1985, Science.

[35]  E. Eisenberg,et al.  The rate-limiting step in the actomyosin adenosinetriphosphatase cycle. , 1984, Biochemistry.

[36]  E. Eisenberg,et al.  Mechanism of actomyosin adenosine triphosphatase. Evidence that adenosine 5'-triphosphate hydrolysis can occur without dissociation of the actomyosin complex. , 1979, Biochemistry.

[37]  P. Wagner Effect of skeletal muscle myosin light chain 2 on the Ca2+-sensitive interaction of myosin and heavy meromyosin with regulated actin. , 1984, Biochemistry.

[38]  T. L. Hill,et al.  Theoretical formalism for the sliding filament model of contraction of striated muscle. Part I. , 1974, Progress in biophysics and molecular biology.

[39]  B. Brenner,et al.  Equatorial x-ray diffraction from single skinned rabbit psoas fibers at various degrees of activation. Changes in intensities and lattice spacing. , 1985, Biophysical journal.

[40]  E. Eisenberg,et al.  Subfragment 1 of myosin: adenosine triphophatase activation by actin. , 1968, Biochemistry.