Dichloroacetate accelerates the fall in intracellular PO2 at onset of contractions in Xenopus single muscle fibers.
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.
Howlett
Richard A
RA
Department of Medicine, University of California, San Diego, La Jolla, California 92093-0623, USA. rhowlett@ucsd.edu
Hogan
Michael C
MC
D000818:Animals; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D007700:Kinetics; D009119:Muscle Contraction; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D013997:Time Factors; D014981:Xenopus
D003999:Dichloroacetic Acid; D010100:Oxygen