title: Rate constant of muscle force redevelopment reflects cooperative activation as well as cross-bridge kinetics.
abstract: The rate of muscle force redevelopment after release-restretch protocols has previously been interpreted using a simple two-state cross-bridge cycling model with rate constants for transitions between non-force-bearing and force-bearing states, f, and between force-bearing and non-force-bearing states, g. Changes in the rate constant of force redevelopment, as with varying levels of Ca2+ activation, have traditionally been attributed to Ca(2+)-dependent f. The current work adds to this original model a state of unactivated, noncycling cross-bridges. The resulting differential equation for activated, force-bearing cross-bridges, Ncf, was Ncf = -[g+f(K/(K + 1))] Ncf+f(K/(K + 1))NT, where K is an equilibrium constant defining the distribution between cycling and noncycling cross-bridges and NT is the total number of cross-bridges. Cooperativity by which force-bearing cross-bridges participate in their own activation was introduced by making K depend on Ncf. Model results demonstrated that such cooperativity, which tends to enhance force generation at low levels of Ca2+ activation, has a counter-intuitive effect of slowing force redevelopment. These dynamic effects of cooperativity are most pronounced at low Ca2+ activation. As Ca2+ activation increases, the cooperative effects become less important to the dynamics of force redevelopment and, at the highest levels of Ca2+ activation, the dynamics of force redevelopment reflect factors other than cooperative mechanisms. These results expand on earlier interpretations of Ca2+ dependence of force redevelopment; rather than Ca(2+)-dependent f, Ca(2+)-dependent force redevelopment arises from changing expressions of cooperativity between force-bearing cross-bridges and activation.
authors.affiliation: Department of Veterinary and Comparative Anatomy, Physiology, and Pharmacology, Washington State University, Pullman 99164, USA. cvselkbc@vetmed.wsu.edu
authors.forename: K
authors.initials: K
authors.lastname: Campbell
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology; D006321:Heart / Q000502:physiology*; D007700:Kinetics; D008954:Models, Biological; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000502:physiology*; D009200:Myocardial Contraction
chemical_list: D002118:Calcium