The adjustment of skeletal muscle oxidative phosphorylation in response to higher metabolic rates is characterized by a delay followed by a monoexponential rise to steady state where this can be achieved. The setting of this response is due, in part, to a complex myriad of events including matching of convective, and conductive (facilitated via myoglobin) 02 delivery to demand, alterations in redox and phosphorylation state, and increased mitochondrial activation. While exercise training may speed V02 kinetics, disease states such as heart failure and diabetes slow V02 kinetics. Metabolic responses to muscle contractions are determined, in part, by muscle fiber type composition and recent data suggests that nitric oxide (NO), a molecule involved in exercise hyperemia, also impairs mitochondrial function. The present proposal aims to study V02 dynamics in isolated skeletal myocytes (thus, independent of Q02 issues) to elucidate specific roles of muscle fiber type, NO and myoglobin. Specifically, the following hypotheses are proposed regarding the transition from rest to electrically stimulated contraction: 1) Slow oxidative myocytes will have faster V02 kinetics compared with less oxidative, more glycolytic fibers and the speed of the kinetics will correlate positively with mitochondrial volume density, 2) Inhibition of NO synthase will result in faster V02 kinetics and conversely, exogenous NO will slow the V02 response, and 3) Absence of myoglobin will significantly slow V02 kinetics.

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 #
1F32AR048461-01
Application #
6442800
Study Section
Special Emphasis Panel (ZRG1-SSS-3 (20))
Program Officer
Lymn, Richard W
Project Start
2002-03-01
Project End
Budget Start
2002-03-01
Budget End
2003-02-28
Support Year
1
Fiscal Year
2002
Total Cost
$36,592
Indirect Cost
Name
University of California San Diego
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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Kindig, Casey A; Stary, Creed M; Hogan, Michael C (2005) Effect of dissociating cytosolic calcium and metabolic rate on intracellular PO2 kinetics in single frog myocytes. J Physiol 562:527-34
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Kindig, Casey A; Howlett, Richard A; Hogan, Michael C (2005) Effect of contractile duration on intracellular PO2 kinetics in Xenopus single skeletal myocytes. J Appl Physiol 98:1639-45
Kindig, Casey A; Walsh, Brandon; Howlett, Richard A et al. (2005) Relationship between intracellular PO2 recovery kinetics and fatigability in isolated single frog myocytes. J Appl Physiol 98:2316-9
Kindig, Casey A; Howlett, Richard A; Stary, Creed M et al. (2005) Effects of acute creatine kinase inhibition on metabolism and tension development in isolated single myocytes. J Appl Physiol 98:541-9
Haseler, Luke J; Kindig, Casey A; Richardson, Russell S et al. (2004) The role of oxygen in determining phosphocreatine onset kinetics in exercising humans. J Physiol 558:985-92
Richardson, Troy E; Kindig, Casey A; Musch, Timothy I et al. (2003) Effects of chronic heart failure on skeletal muscle capillary hemodynamics at rest and during contractions. J Appl Physiol 95:1055-62

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