A model for the interaction of muscle cross-bridges with ligands which compete with ATP.
A model is presented to describe the inhibition of muscle fiber contraction by ligands that compete with MgATP. Two ligands, adenosine 5' (beta, gamma-imido) triphosphate (AMPPNP) and pyrophosphate (PPi), decrease the force developed in isometric contractions and act as weak competitive inhibitors of the maximum velocity of contraction (Pate & Cooke, 1985). These observations provide information on the energetics of actomyosin ligand states at the end of the power-stroke where MgATP dissociates the myosin cross-bridge from actin, and they are analysed in terms of a seven state model of cross-bridge kinetics. The model can reconcile the observations that these ligands bind tightly to fibers, Kd = 10(-4) M, while they are only weak inhibitors of fiber velocity, Ki = 2 X 10(-3) M. It provides a reasonable fit to the data and leads to several conclusions concerning the properties of the cross-bridge states. The states with bound ligand are shifted axially so that they occur earlier in the power-stroke than the nucleotide-free rigor state. This shift also explains the axial lengthening seen upon addition of ligands to rigor fibers. We can conclude that these ligands cause small perturbations in the cross-bridge configuration rather than large shifts. A second conclusion is that cross-bridges do not detach from actin during their power-strokes. Instead they traverse the entire length of the power stroke and are detached only at the end, leading to the suggestion that the cycling of bridges in isometric fibers is due to fluctuations in the relative positions of thick and thin filaments. With some further assumptions, the model also explains many of the rate constants and equilibrium constants of the actin-myosin-ligand interaction that have been measured in solution.
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000266:Adenylyl Imidodiphosphate / Q000494:pharmacology; D000818:Animals; D011756:Diphosphates / Q000494:pharmacology; D007700:Kinetics; D008024:Ligands / Q000494:pharmacology*; D008954:Models, Biological; D009119:Muscle Contraction / Q000187:drug effects*; D013816:Thermodynamics
D011756:Diphosphates; D008024:Ligands; D000266:Adenylyl Imidodiphosphate; D000255:Adenosine Triphosphate