title: Regulation of shortening velocity by cross-bridge phosphorylation in smooth muscle.
abstract: We have proposed a model that incorporates a dephosphorylated "latch bridge" to explain the mechanics and energetics of smooth muscle. Cross-bridge phosphorylation is proposed as a prerequisite for cross-bridge attachment and rapid cycling. Features of the model are 1) myosin light chain kinase and phosphatase can act on both free and attached cross bridges, 2) dephosphorylation of an attached phosphorylated cross bridge produces a noncycling "latch bridge," and 3) latch bridges have a slow detachment rate. This model quantitatively predicts the latch state: stress maintenance with reduced phosphorylation, cross-bridge cycling rates, and ATP consumption. In this study, we adapted A. F. Huxley's formulation of crossbridge cycling (A. F. Huxley, Progr. Biophys. Mol. Biol. 7: 255-318, 1957) to the latch-bridge model to predict the relationship between isotonic shortening velocity and phosphorylation. The model successfully predicted the linear dependence of maximum shortening velocity at zero external load (V0) on phosphorylation, as well as the family of stress-velocity curves determined at different times during a contraction when phosphorylation values varied. The model implies that it is unnecessary to invoke an internal load or multiple regulatory mechanisms to explain regulation of V0 in smooth muscle.
authors.affiliation: Department of Physiology, School of Medicine, University of Virginia, Charlottesville 22908.
authors.forename: C M
authors.initials: CM
authors.lastname: Hai
authors.forename: R A
authors.initials: RA
authors.lastname: Murphy
mesh_terms: D000465:Algorithms; D008954:Models, Biological; D009130:Muscle, Smooth / Q000502:physiology*; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D010766:Phosphorylation; D011487:Protein Conformation; D012984:Software
chemical_list: D009219:Myosin-Light-Chain Kinase