Substantial ATP supply by glycolysis is thought to reflect cellular anoxia
in vertebrate muscle. An alternative hypothesis is that the lactate generat
ed during contraction reflects sustained glycolytic ATP supply under well-o
xygenated conditions. We distinguished these hypotheses by comparing intrac
ellular glycolysis during anoxia to lactate efflux from muscle during susta
ined, aerobic contractions. We examined the tailshaker muscle of the rattle
snake because of its uniform cell properties, exclusive blood circulation,
and ability to sustain rattling for prolonged periods. Here we show that gl
ycolysis is independent of the O-2 level and supplies one-third of the high
ATP demands of sustained tailshaking, Fatigue is avoided by rapid H+ and l
actate efflux resulting from blood flow rates that are among the highest re
ported for vertebrate muscle. These results reject the hypothesis that glyc
olysis necessarily reflects cellular anoxia. Instead, they demonstrate that
glycolysis can provide a high and sustainable supply of ATP along with oxi
dative phosphorylation without muscle fatigue.