Acute inhibition of respiratory capacity of muscle reduces peak oxygen consumption.
Electron transport capacity of skeletal muscle was inhibited in situ in an acute dose-dependent manner with myxothiazol, a tight-binding inhibitor of ubiquinone-cytochrome c reductase, complex III of the respiratory chain. Peak oxygen consumption of rat hindlimb muscle was determined via consecutive 10-min isometric contraction (100 ms at 100 Hz) periods of increasing energy demands (4, 8, 15, 30, 45, and 60 tetani/min), using an isolated hindlimb preparation perfused with a high oxygen delivery (approximately 6-8 mumol.min-1.g-1). Peak oxygen consumption decreased from 4.61 +/- 0.19 mumol.min-1.g-1 (control) in a dose-dependent manner to 0.73 +/- 0.07 mumol.min-1.g-1 at 0.50 microM myxothiazol in blood. Oxygen extraction decreased from 65 to 12% of delivered oxygen. Furthermore, the reduction in peak respiratory rate became evident at lower energy demands of the contraction sequence. Myxothiazol inhibition of respiration was not dependent on the presence of muscle contractions but was evident when mitochondria were uncoupled with carbonyl cyanide m-chlorophenylhydrazone. A 50% effective dosage (ED50) of 0.21 microM myxothiazol for inhibition of peak oxygen consumption closely resembled the inhibition of NADH-cytochrome c reductase activity (ED50 of 0.27 microM) determined from homogenates of the same muscles. This suggests that the peak oxygen consumption of skeletal muscle is tightly coupled to the capacity for electron transport evaluated by flux through NADH-cytochrome c reductase. If the enzyme activity measured in vitro correctly represents available enzymatic capacity within contracting muscle, approximately 75% of electron transport capacity for handling reducing equivalents generated from NADH is utilized during peak oxygen consumption of rat hindlimb muscle contracting in situ.
McAllister
R M
RM
Department of Physiology, State University of New York, Syracuse 13210.
Terjung
R L
RL
D000818:Animals; D004558:Electric Stimulation; D004579:Electron Transport; D007537:Isometric Contraction; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000502:physiology*; D009245:NADH Dehydrogenase / Q000378:metabolism; D009928:Organ Specificity; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013384:Succinate Cytochrome c Oxidoreductase / Q000378:metabolism
D013384:Succinate Cytochrome c Oxidoreductase; D009245:NADH Dehydrogenase