Smooth muscle contraction is essential to the normal function of many organ systems within 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. An intriguing mechanical property of smooth muscle is its ability to produce as much force per cross-sectional area of muscle as skeletal muscle with far less myosin (i.e. fewer cross-bridges). These data suggest that smooth muscle cross-bridges may generate more average force than skeletal muscle cross-bridges. Since force generation in these two muscle types is believed to result from the cyclic interaction of myosin cross-bridges with actin, smooth muscle cross-bridges may achieve a higher average force by spending a larger fraction of each cross-bridge cycle attached to actin in a high force producing state (i.e. higher duty cycle). To address this question, an in vitro motility assay will be used to directly measure both the velocity and force of a single fluorescently labeled actin filament as it slides over a myosin coated glass coverslip. This proposal begins to characterize smooth muscle force generation at the molecular level.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
1R01AR042231-01
Application #
3162590
Study Section
Physiology Study Section (PHY)
Project Start
1993-08-01
Project End
1998-07-31
Budget Start
1993-08-01
Budget End
1994-07-31
Support Year
1
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Vermont & St Agric College
Department
Type
Schools of Medicine
DUNS #
066811191
City
Burlington
State
VT
Country
United States
Zip Code
05405
Malghani, M S; Yang, J; Wu, J (1998) Generation and growth of bilayer defects induced by ultrasound. J Acoust Soc Am 103:1682-5
Guilford, W H; Warshaw, D M (1998) The molecular mechanics of smooth muscle myosin. Comp Biochem Physiol B Biochem Mol Biol 119:451-8
Warshaw, D M; Hayes, E; Gaffney, D et al. (1998) Myosin conformational states determined by single fluorophore polarization. Proc Natl Acad Sci U S A 95:8034-9
VanBuren, P; Begin, K; Warshaw, D M (1998) Fluorescent phalloidin enables visualization of actin without effects on myosin's actin filament sliding velocity and hydrolytic properties in vitro. J Mol Cell Cardiol 30:2777-83
Dupuis, D E; Guilford, W H; Wu, J et al. (1997) Actin filament mechanics in the laser trap. J Muscle Res Cell Motil 18:17-30
Guilford, W H; Dupuis, D E; Kennedy, G et al. (1997) Smooth muscle and skeletal muscle myosins produce similar unitary forces and displacements in the laser trap. Biophys J 72:1006-21
VanBuren, P; Waller, G S; Harris, D E et al. (1994) The essential light chain is required for full force production by skeletal muscle myosin. Proc Natl Acad Sci U S A 91:12403-7
VanBuren, P; Work, S S; Warshaw, D M (1994) Enhanced force generation by smooth muscle myosin in vitro. Proc Natl Acad Sci U S A 91:202-5
Siegman, M J; Mooers, S U; Warren, T B et al. (1994) Comparison of the effects of 2,3-butanedione monoxime on force production, myosin light chain phosphorylation and chemical energy usage in intact and permeabilized smooth and skeletal muscles. J Muscle Res Cell Motil 15:457-72