title: Regulation of a smooth muscle contraction: a hypothesis based on skinned fiber studies.
abstract: It seems clear that a simple Ca2+ dependent switch (MLC phosphorylation) cannot completely explain all of the disparate mechanical and energetic results obtained under numerous experimental conditions in numerous laboratories. Some of the problems of the simple switch model are that: 1. Force can be developed in the complete absence of increases in MLC phosphorylation; 2. Crossbridge cycling rate, as measured by either shortening velocity or directly by ATPase activity, can be regulated independent of changes in MLC phosphorylation; and 3. Ca2+ can directly influence both force and crossbridge cycling rate. Thus, we believe that there are two distinct Ca2+ dependent regulatory systems which normally act in parallel to contract smooth muscle. One of these is the Ca2+ dependent MLC phosphorylation-dephosphorylation. system which is likely to be responsible for the rapid development of force. The other is the hypothesized Ca2+ dependent system which is probably responsible for the slow development of force as well as the maintenance of previously developed force, represented in Figure 5 as K8. This second system involves a calmodulin-like protein with a higher Ca2+ sensitivity than that for the Ca(2+)-calmodulin-MLC kinase system. Under most conditions, the total force attained by smooth muscle in response to stimulation is the result of the concerted activation of both of these regulatory systems. The available information is consistent with this hypothesis of two regulatory systems functioning in parallel. In addition to the information presented in this chapter, work from a number of laboratories (Moreland and Ford, 1982; Fujiwara et al., 1989; Kitazawa et al., 1989; Somlyo et al., 1989; Kubota et al., 1990; Kitazawa and Somlyo, this volume) have suggested the possibility that a regulated MLC phosphatase may functionally alter the Ca2+ sensitivity of the contractile filaments. There is evidence suggesting that the sensitivity of MLC kinase to activation by Ca2+ and calmodulin may be regulated (Stull et al., this volume). Protein kinase C has been postulated to play an important role in the regulation of myofilament Ca2+ sensitivity (Nishimura et al., this volume). MgADP has been suggested to affect the kinetics of latchbridge attachment and detachment (Kerrick and Hoar, 1987; Nishimura and van Breemen, 1989). Cooperativity between crossbridges as described by Somlyo et al. (1988) and Siegman et al. (this volume) might also be an important component in the regulation of smooth muscle contraction.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Bockus Research Institute, Graduate Hospital, Philadelphia, PA 19146.
authors.forename: R S
authors.initials: RS
authors.lastname: Moreland
authors.forename: J W
authors.initials: JW
authors.lastname: Pott
authors.forename: J
authors.initials: J
authors.lastname: Cilea
authors.forename: S
authors.initials: S
authors.lastname: Moreland
mesh_terms: D000818:Animals; D006801:Humans; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000201:enzymology / Q000502:physiology*; D009186:Myelin Sheath / Q000502:physiology; D009219:Myosin-Light-Chain Kinase / Q000502:physiology
chemical_list: D009219:Myosin-Light-Chain Kinase