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Department of Medicine, University of California, San Diego, La Jolla, California 92093-0623
This study investigated the relationship between intracellular PO2 (PIO2) and dichloroacetate (DCA) administration following a significant step-change increase in oxidative metabolism in intact isolated Xenopus single muscle fibers. Single fibers (n = 22) were dissected from the lumbrical muscle, injected with the oxygen-sensitive compound palladium-meso-tetra (4-carboxyphenyl) porphine, and randomly assigned to one of two treatment groups. One group (DCA; n = 12) was incubated for 30 min with 1.2 mM DCA, whereas the second group [control (Con); n = 10] was incubated for 30 min in Ringer solution only. After incubation, fibers were electrically stimulated to elicit tetanic contractions (0.5 Hz) for 2 min during which PIO2 was monitored. PIO2 before contractions began was 32.0 ± 1.8 and 29.0 ± 1.8 Torr for DCA and Con, respectively, and fell to 6.0 ± 1.3 and 8.8 ± 2.4 Torr (no significant difference), respectively, after steady state was reached. The kinetics of the fall, determined by both the time delay (from the start of contractions to the initial decrease in PIO2) and the tau (63% of the change to a steady state in PIO2), were calculated. In DCA cells, the tau was significantly (P < 0.05) faster than Con (22.1 ± 3.6 vs. 39.7 ± 5.8 s). In contrast, the time delay was not significantly (P > 0.45) different between the two groups (11.4 ± 1.7 vs. 12.6 ± 2.3 s, respectively). The amount of fatigue, reflected by a decrease in force production from initial, was not significantly different between groups. These data suggest that by stimulating pyruvate dehydrogenase with DCA in isolated single skeletal muscle cells, the faster fall in PIO2 is indicative of oxidative metabolism being more rapidly activated. This is the first evidence that oxygen uptake at the onset of contractions may be altered by DCA during moderate- to high-intensity contractile activity.
oxygen kinetics; oxidative metabolism; pyruvate dehydrogenase; metabolic inertia; fatigue
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