title: Physiological consequences of thin filament cooperativity for vertebrate striated muscle contraction: a theoretical study.
abstract: Bindings of both myosin and Ca(2+) to the thin filament of vertebrate striated muscle are known to be strongly cooperative. Here the relation between these two sources of cooperativity and their consequences for physiological properties are assessed by comparing two models, with and without Monod-type myosin-binding cooperativity. In both models a thin filament regulatory unit (RU) is in either 'off' or 'on' state, and the equilibrium between them (K (on)) is [Ca(2+)]-dependent. The calculations predict the following: (1) In both models, myosin binding stabilizes the RU in the 'on' state, causing troponin to trap Ca(2+). This stabilization in turn increases the Ca(2+)-binding cooperativity, ensuring efficient regulation to occur in a narrow [Ca(2+)] range. (2) In the cooperative model, the RU is stabilized with a relatively low myosin affinity for actin (K approximately approximately 1), while the non-cooperative model requires a much higher affinity (K approximately approximately 10) to produce the same effect. (3) The cooperative model reproduces the known effects of [Ca(2+)] on the rate of force development and shortening velocity with a low K, but again the non-cooperative model requires a higher value. (4) Because of the finite value of K (on), the thin filaments can never be fully activated by increasing [Ca(2+)], indicating that contracting muscles are under strong influence of thin-filament cooperativity even at saturating [Ca(2+)]. Interpretation of data on muscle mechanics without considering these cooperative effects could therefore lead to a substantial (10-fold) overestimate of cross-bridge binding properties.
authors.affiliation: Research and Utilization Division, SPring-8, Japan Synchrotron Radiation Research Institute, 1-1-1 Kouto, Sayo-cho, Sayo-gun, Hyogo 679-5198, Japan. iwamoto@spring8.or.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Iwamoto
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D009119:Muscle Contraction / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology*; D009218:Myosins / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D013314:Stress, Mechanical; D014336:Troponin / Q000378:metabolism*
chemical_list: D014336:Troponin; D009218:Myosins; D002118:Calcium