Smooth muscle contraction is essential to normal function of many organ systems in the body. Therefore, an understanding of its normal contractile process is required before studying disease states such as hypertension in which smooth muscle function may be abnormal. Smooth muscle is characterized by its slow shortening velocity and economical useage of ATP during force production. These contractile properties may reflect both the mechanics of the basic force generating element, the myosin crossbridge, and its cyclic interaction with actin. To characterize crossbridge properties in smooth muscle, stare-of-the-art techniques will be used to measure mechanical responses from a single smooth muscle cell, isolated from the toad stomach. The single cell approach will avoid the heterogeneity of cellular responses that can occur in multicellular tissue preparations. To correlate a smooth muscle cell's contractile capabilities to its crossbridge properties, changes in cell length will be used as a means of probing the crossbridge cycle. In addition to mechanical perturbations, membrane permeabilized cells will provide the opportunity to modify the cell's interior chemical environment. Thus changes in the cell's free intracellular concentrations of specific ions (e.g. MgATP) and the effect these chemical perturbations have upon cell mechanics will help identify the specific steps in the crossbridge cycle. Finally, a mathematical model of the crossbridge cycle in smooth muscle, that incorporates the mechanical data obtained in this proposal, will be used to formulate a view of the crossbridge cycle in smooth muscle to help explain smooth muscle's slow, economical contraction.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
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Physiology Study Section (PHY)
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University of Vermont & St Agric College
Schools of Medicine
United States
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Harris, D E; Work, S S; Wright, R K et al. (1994) Smooth, cardiac and skeletal muscle myosin force and motion generation assessed by cross-bridge mechanical interactions in vitro. J Muscle Res Cell Motil 15:11-9
Harris, D E; Warshaw, D M (1993) Smooth and skeletal muscle actin are mechanically indistinguishable in the in vitro motility assay. Circ Res 72:219-24
Harris, D E; Warshaw, D M (1993) Smooth and skeletal muscle myosin both exhibit low duty cycles at zero load in vitro. J Biol Chem 268:14764-8
Work, S S; Warshaw, D M (1992) Computer-assisted tracking of actin filament motility. Anal Biochem 202:275-85
Harris, D E; Warshaw, D M; Periasamy, M (1992) Nucleotide sequences of the rabbit alpha-smooth-muscle and beta-non-muscle actin mRNAs. Gene 112:265-6
Harris, D E; Warshaw, D M (1991) Length vs. active force relationship in single isolated smooth muscle cells. Am J Physiol 260:C1104-12
Harris, D E; Warshaw, D M (1990) Slowing of velocity during isotonic shortening in single isolated smooth muscle cells. Evidence for an internal load. J Gen Physiol 96:581-601
Yamakawa, M; Harris, D E; Fay, F S et al. (1990) Mechanical transients of single toad stomach smooth muscle cells. Effects of lowering temperature and extracellular calcium. J Gen Physiol 95:697-715
Warshaw, D M; Yamakawa, M; Harris, D (1989) Evidence for an internal load in single smooth muscle cells. Prog Clin Biol Res 315:329-45
Warshaw, D M; Rees, D D; Fay, F S (1988) Characterization of cross-bridge elasticity and kinetics of cross-bridge cycling during force development in single smooth muscle cells. J Gen Physiol 91:761-79

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