The wide acceptance of the crossbridge/sliding filament theory of skeletal muscle contraction has led to many efforts to extend it to the case of smooth muscle. Substantial evidence is accumulating that this extension is generally valid; however, major differences do exist in the cellular control mechanisms and mechanical behavior. Smooth muscle function appears to involve special properties of the myosin crossbridges; metabolic cost of force maintenance is relatively low, and resistance to stretch is enhanced during relaxation. It is the long-term goal of this research to understand the relationship between the known biochemical regulatory mechanisms and unique mechanical features of the muscle by using mechanical methods which will provide a new perspective on these special properties. Smooth muscle from rat uterus and rabbit mesotubarium will be stimulated electrically or by potassium depolarization. The complex stiffness (which appears to reflect, and be modified by, changes in hypothesized crossbridge number and mechanical state) will be measured and analyzed during contraction and relaxation by examining the amplitude and phase of force responses to very small sinusoidal length oscillations. These will be applied to muscle in a variety of contractile states. The responses are sensitive to the oscillation frequency and the putative mechanical transitions in the crossbridge cycle. In some cases the regulatory system will be manipulated by varying calcium and mgATP in muscles which have been chemically """"""""skinned"""""""" by using detergents or glycerol. Special attention will be paid to states mimicking relaxation in intact muscle (i.e., calcium or substrate removal). The contraction-phase determinants of the load-bearing processes of relaxing muscle will also be studied to identify factors which may influence the formation of special detachment-resistants of the load-bearing processes of relaxing muscle will also be studied to identify factors which may influence the formation of special detachment-resistant crossbridge states. Understanding the control of contraction and relaxation of reproductive smooth muscle is important in the critical health-related area of normal uterine function during labor, especially as it bears upon the problems of premature labor and incomplete relaxation during labor. Extrapolation of the results of this work may also benefit our understanding of other smooth-muscle-related problems such as hypertension and other vascular problems and certain respiratory, urological, and intestinal disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
5R01AM034385-02
Application #
3153156
Study Section
Physiology Study Section (PHY)
Project Start
1984-07-01
Project End
1987-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Type
Schools of Medicine
DUNS #
005436803
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
Tanner, J A; Haeberle, J R; Meiss, R A (1988) Regulation of glycerinated smooth muscle contraction and relaxation by myosin phosphorylation. Am J Physiol 255:C34-42
Meiss, R A (1987) Stiffness of active smooth muscle during forced elongation. Am J Physiol 253:C484-93
Meiss, R A (1987) Crossbridge properties studied during forced elongation of active smooth muscle. Prog Clin Biol Res 245:347-56