title: Phosphate and ADP differently inhibit coordinated smooth muscle myosin groups.
abstract: Actin filaments propelled in vitro by groups of skeletal muscle myosin motors exhibit distinct phases of active sliding or arrest, whose occurrence depends on actin length (L) within a range of up to 1.0 μm. Smooth muscle myosin filaments are exponentially distributed with ≈150 nm average length in vivo--suggesting relevance of the L-dependence of myosin group kinetics. Here, we found L-dependent actin arrest and sliding in in vitro motility assays of smooth muscle myosin. We perturbed individual myosin kinetics with varying, physiological concentrations of phosphate (Pi, release associated with main power stroke) and adenosine diphosphate (ADP, release associated with minor mechanical step). Adenosine triphosphate was kept constant at physiological concentration. Increasing [Pi] lowered the fraction of time for which actin was actively sliding, reflected in reduced average sliding velocity (ν) and motile fraction (fmot, fraction of time that filaments are moving); increasing [ADP] increased the fraction of time actively sliding and reduced the velocity while sliding, reflected in reduced ν and increased fmot. We introduced specific Pi and ADP effects on individual myosin kinetics into our recently developed mathematical model of actin propulsion by myosin groups. Simulations matched our experimental observations and described the inhibition of myosin group kinetics. At low [Pi] and [ADP], actin arrest and sliding were reflected by two distinct chemical states of the myosin group. Upon [Pi] increase, the probability of the active state decreased; upon [ADP] increase, the probability of the active state increased, but the active state became increasingly similar to the arrested state.
authors: Department of Physiology, McGill University, Montréal, Québec, Canada; Centre for Applied Mathematics in Bioscience and Medicine, Montréal, Québec, Canada; Meakins-Christie Laboratories, Montréal, Québec, Canada. Electronic address: lennart.hilbert@mail.mcgill.ca.
authors: Lennart
authors: L
authors: Hilbert
authors: Department of Physiology, McGill University, Montréal, Québec, Canada; Meakins-Christie Laboratories, Montréal, Québec, Canada.
authors: Zsombor
authors: Z
authors: Balassy
authors: Meakins-Christie Laboratories, Montréal, Québec, Canada.
authors: Nedjma B
authors: NB
authors: Zitouni
authors: Department of Physiology, McGill University, Montréal, Québec, Canada; Centre for Applied Mathematics in Bioscience and Medicine, Montréal, Québec, Canada; Department of Physics, McGill University, Montréal, Québec, Canada; Department of Mathematics, McGill University, Montréal, Québec, Canada.
authors: Michael C
authors: MC
authors: Mackey
authors: Department of Physiology, McGill University, Montréal, Québec, Canada; Meakins-Christie Laboratories, Montréal, Québec, Canada; Department of Medicine, McGill University, Montréal, Québec, Canada; Department of Biomedical Engineering, McGill University, Montréal, Québec, Canada. Electronic address: anne.lauzon@mcgill.ca.
authors: Anne-Marie
authors: AM
authors: Lauzon
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000818:Animals; D002645:Chickens; D003198:Computer Simulation; D007700:Kinetics; D008954:Models, Biological; D009068:Movement; D010710:Phosphates / Q000494:pharmacology*; D024745:Smooth Muscle Myosins / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000199:Actins; D010710:Phosphates; D000244:Adenosine Diphosphate; D024745:Smooth Muscle Myosins
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