Dynamics of Oxygen Uptake in Contracting Single Myocytes

说明：（由申请人提供）：骨骼肌的调整

DESCRIPTION: (provided by applicant): 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.