This research seeks to understand the metabolic basis of muscle fatigue by examining the quantitative relationship between energy metabolism and fatigability at the level of individual motor units.
The specific aims are: 1) to determine the enzymatic correlates of fatigue under the appropriate stimulus conditions, 2) to determine the effect of reduced use on fatigue resistance, and 3) to determine the metabolic intermediaries associated with fatigue.
The first aim should reveal the enzymes of energy metabolism which govern the ability of muscle to maintain a given force output;
the second aims tests the stability of these functional correlates under conditions of induced muscle atrophy; the third measures dynamic metabolic events during fatigue which should correspond to the enzymatic phenotype. The experimental approach involves the electrophysiological characterization (i.e., axonal condition velocity, electromyography, force and fatigability) of functionally isolated motor units. The subsequent biochemical analyses of the constituent muscle fibers include: activities of enzymes (adenylokinase, creatine kinase, lactate dehydrogenase, malate dehydrogenase and beta-hydroxyacyl CoA dehydrogenase) and concentrations of phosphogens and metabolites of energy metabolism using single-fiber microflurometric assays and myosin isoform characterization using single-fiber polyacrylamide gel electrophoresis. Motor unit fibers will be identified by both glycogen depletion and 2-deoxyglucose uptake of selectively activated motor axons. Associations will be measured with statistical analyses. The proposal will provide fundamental information on the biochemical-physiological interactions that underlie muscle performance in health and in muscle disease such as Duchenne Dystrophy, Limb-Girdle Dystrophy, Motoneuron Disease, Myasthenia Gravis, Thyrotoxicosis, Progressive Muscle Atrophy, and Spinal Muscular Atrophy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS020762-04
Application #
3401329
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1986-04-01
Project End
1994-03-31
Budget Start
1989-04-01
Budget End
1990-03-31
Support Year
4
Fiscal Year
1989
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
Stauffer, E K; McDonagh, J C; Hornby, T G et al. (2007) Historical reflections on the afterhyperpolarization--firing rate relation of vertebrate spinal neurons. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 193:145-58
Gorman, R B; McDonagh, J C; Hornby, T G et al. (2005) Measurement and nature of firing rate adaptation in turtle spinal neurons. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 191:583-603
Stauffer, E K; Stuart, D G; McDonagh, J C et al. (2005) Afterhyperpolarization-firing rate relation of turtle spinal neurons. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 191:135-46
Callister, Robert J; Sesodia, Sanjay; Enoka, Roger M et al. (2004) Fatigue of rat hindlimb motor units: biochemical-physiological associations. Muscle Nerve 30:714-26
McDonagh, J C; Callister, R J; Favron, M L et al. (2004) Resistance to disuse atrophy in a turtle hindlimb muscle. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 190:321-9
Callister, R J; Donnelly, R P; Pierce, P A et al. (1996) Motor pool organization of the external gastrocnemius muscle in the turtle, Pseudemys (Trachemys) scripta elegans. J Morphol 227:171-83
Callister, R J; Laidlaw, D H; Stuart, D G (1995) A commentary on the segmental motor system of the turtle: implications for the study of its cellular mechanisms and interactions. J Morphol 225:213-27
Laidlaw, D H; Callister, R J; Stuart, D G (1995) Fiber-type composition of hindlimb muscles in the turtle, Pseudemys (Trachemys) scripta elegans. J Morphol 225:193-211
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

Showing the most recent 10 out of 15 publications