title: Substrate and product dependence of force and shortening in fast and slow smooth muscle.
abstract: To explore the molecular mechanisms responsible for the variation in smooth muscle contractile kinetics, the influence of MgATP, MgADP, and inorganic phosphate (P(i)) on force and shortening velocity in thiophosphorylated "fast" (taenia coli: maximal shortening velocity Vmax = 0.11 ML/s) and "slow" (aorta: Vmax = 0.015 ML/s) smooth muscle from the guinea pig were compared. P(i) inhibited active force with minor effects on the V(max). In the taenia coli, 20 mM P(i) inhibited force by 25%. In the aorta, the effect was markedly less (< 10%), suggesting differences between fast and slow smooth muscles in the binding of P(i) or in the relative population of P(i) binding states during cycling. Lowering of MgATP reduced force and V(max). The aorta was less sensitive to reduction in MgATP (Km for Vmax: 80 microM) than the taenia coli (Km for Vmax: 350 microM). Thus, velocity is controlled by steps preceding the ATP binding and cross-bridge dissociation, and a weaker binding of ATP is not responsible for the lower V(max) in the slow muscle. MgADP inhibited force and V(max). Saturating concentrations of ADP did not completely inhibit maximal shortening velocity. The effect of ADP on Vmax was observed at lower concentrations in the aorta compared with the taenia coli, suggesting that the ADP binding to phosphorylated and cycling cross-bridges is stronger in slow compared with fast smooth muscle.
authors.affiliation: Department of Physiological Sciences, Lund University, Tornavägen 10, BMC F11, S-22184 Lund, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Löfgren
authors.forename: U
authors.initials: U
authors.lastname: Malmqvist
authors.forename: A
authors.initials: A
authors.lastname: Arner
mesh_terms: D000199:Actins / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D003106:Colon / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology*; D018656:Muscle Fibers, Fast-Twitch / Q000201:enzymology; D018657:Muscle Fibers, Slow-Twitch / Q000201:enzymology; D009130:Muscle, Smooth / Q000166:cytology / Q000502:physiology*; D009218:Myosins / Q000378:metabolism; D010710:Phosphates / Q000494:pharmacology
chemical_list: D000199:Actins; D010710:Phosphates; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; D009218:Myosins