This project will use NMR spectroscopy and other methods to examine the role of changes in energetically important metabolites (e.g., PCr, ATP, inorganic phosphate, lactic acid, pH) in the regulation of mammalian skeletal muscle metabolism. The major specific aim is to test competing models of the control of respiration in intact muscle. This will be accomplished by examining the relationships between cytoplasmic phosphate metabolites, mitochondrial NADH/NAD ratio (measured by surface fluorescence) and respiration in cat fast (biceps) and slow-twitch (soleus) muscles at rest and during and after stimulation. Additional studies will examine the effects of experimentally-imposed changes in pH, PCr, ATP, and substrate supply on these relationships. These experiments will also examine the effects of imposed changes in pH and phosphate metabolites on regulation of glycolysis and force development. Additional experiments will examine whether there is functionally-- significant compartmentation of adenine nucleotides in muscle, test the validity of 1H-NMR methods for measurement of lactic acid, and define the relationships between pH and lactic acid during recovery after muscle stimulation. A key feature of these studies compared to other NMR studies of muscle is the use of well-characterized perfused muscle preparations, which enables experimental manipulations not possible in muscles in situ. The results will advance our basic understanding of muscle metabolism, as well as provide essential background for the rational design and interpretation of clinical NMR studies of muscle.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
2R01AR038972-04A1
Application #
3159024
Study Section
Physiology Study Section (PHY)
Project Start
1987-07-01
Project End
1995-03-31
Budget Start
1991-04-01
Budget End
1992-03-31
Support Year
4
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Michigan State University
Department
Type
Schools of Medicine
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824