Skeletal muscle is a complex tissue capable increasing its metabolic rate several hundred fold in a matter of seconds. In order to meet energetic demands, skeletal muscle can form ATP through multiple pathways (i.e., PCr hydrolysis, anaerobic glycolysis, and oxidative phosphorylation). Each pathway offers a unique combination of maximal ATP production rate and capacity, and all three must work in concert for effective muscle function. Elucidating the complex integration of these pathways is crucial to the understanding of muscle function in both healthy and diseased states. Although extensive research has been conducted on the regulation and integration of these pathways, several key questions remain unanswered. Part of the reason for this difficulty is due to the techniques used to study skeletal muscle metabolism. For example, many in vitro measurements (e.g., enzyme assays, isolated mitochondria) do not allow the study of integrated muscle function, whereas the use of whole muscle preparations can be confounded by issues such as blood flow and fiber heterogeneity. The isolated fiber technique offers a unique opportunity to study intact skeletal muscle in a controlled environment. Therefore, the isolated fiber technique will be used to: 1.) determine the rate of onset kinetics of glycolysis in different fiber types, 2). determine the role of metabolic channeling in setting the onset kinetics of oxidative phosphorylation, and 3.) determine the intracellular PO2 at which respiration becomes O2 dependent. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32AR053219-01A1
Application #
6936796
Study Section
Special Emphasis Panel (ZRG1-F10 (20))
Program Officer
Nuckolls, Glen H
Project Start
2005-05-01
Project End
2006-04-30
Budget Start
2005-05-01
Budget End
2006-04-30
Support Year
1
Fiscal Year
2005
Total Cost
$49,928
Indirect Cost
Name
University of California San Diego
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Koga, S; Wüst, R C I; Walsh, B et al. (2013) Increasing temperature speeds intracellular PO2 kinetics during contractions in single Xenopus skeletal muscle fibers. Am J Physiol Regul Integr Comp Physiol 304:R59-66
Walsh, B; Howlett, R A; Stary, C M et al. (2006) Measurement of activation energy and oxidative phosphorylation onset kinetics in isolated muscle fibers in the absence of cross-bridge cycling. Am J Physiol Regul Integr Comp Physiol 290:R1707-13