The objective of our work is to understand the influences affecting the metabolic capacity of skeletal muscle. While it is clear that innervation is a critical element in normal development and maintenance of muscle, the extent to which innervation can dominate over factors intrinsic to muscle and its environment, and indeed, the nature of the neural control remains unclear. Fundamental aspects of the neural influences on muscle will be addressed under four major topics: 1) Biochemical differentiation during development; 2) Biochemical transformations in mature muscle, particularly with artificial stimulation and exercise; 3) The correlation of muscle biochemistry and the physiological properties of the parent nerve; 4) The biochemical nature of muscle diseases including those with alterations of the nervous system. In this research we propose to circumvent an inherent complication in the study of nerve-muscle interactions. Skeletal muscle is an intimate mixture of highly specialized fibers which differ greatly in biochemical properties. Fibers lying next to each other may vary as much as 50-fold in some enzyme concentrations, thereby limiting the usefulness of whole muscle studies. The analytical methods employed here provide the capability to analyze individual fibers and, thus, eliminate the problems of interpretation of whole muscle data. A new technique has been developed to measure enzymes in single fibers identified morphologically and histochemically in cross-sections. This in situ identification provides a means to select for study fibers of a given type or to select affected fibers in diseased muscle in which most of the fibers may be unaffected. In addition, it allows the direct comparison of other characteristics of muscle that can be measured in cross-section, particularly those identifiable with specific antibody staining techniques.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK038375-06
Application #
3237732
Study Section
Molecular Cytology Study Section (CTY)
Project Start
1986-08-01
Project End
1989-07-31
Budget Start
1988-08-01
Budget End
1989-07-31
Support Year
6
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Washington University
Department
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Zurlo, F; Nemeth, P M; Choksi, R M et al. (1994) Whole-body energy metabolism and skeletal muscle biochemical characteristics. Metabolism 43:481-6
Sesodia, S; Choksi, R M; Nemeth, P M (1994) Nerve-dependent recovery of metabolic pathways in regenerating soleus muscles. J Muscle Res Cell Motil 15:573-81
Nemeth, P M; Rosser, B W; Choksi, R M et al. (1992) Metabolic response to a high-fat diet in neonatal and adult rat muscle. Am J Physiol 262:C282-6
Hurov, J; Rosser, B W; Baker, K M et al. (1992) Metabolic transitions in rat jaw muscles during postnatal development. J Craniofac Genet Dev Biol 12:98-106
Nemeth, P M; Rosser, B W; Wilkinson, R S (1991) Metabolic and contractile uniformity of isolated motor unit fibres of snake muscle. J Physiol 434:41-55
Wilkinson, R S; Nemeth, P M; Rosser, B W et al. (1991) Metabolic capacity and myosin expression in single muscle fibres of the garter snake. J Physiol 440:113-29
Kelly, A M; Rosser, B W; Hoffman, R et al. (1991) Metabolic and contractile protein expression in developing rat diaphragm muscle. J Neurosci 11:1231-42
Turk, W R; Heller, S L; Norris, B J et al. (1990) Increased muscular beta-hydroxyacyl CoA dehydrogenase with McArdle's disease. Muscle Nerve 13:607-12
Manchester, J K; Chi, M M; Norris, B et al. (1990) Effect of microgravity on metabolic enzymes of individual muscle fibers. FASEB J 4:55-63
Nemeth, P M; Norris, B J; Solanki, L et al. (1989) Metabolic specialization in fast and slow muscle fibers of the developing rat. J Neurosci 9:2336-43

Showing the most recent 10 out of 11 publications