S. Salmons et al., CHANGES IN ATP, PHOSPHOCREATINE, AND 16 METABOLITES IN MUSCLE STIMULATED FOR UP TO 96 HOURS, American journal of physiology. Cell physiology, 40(4), 1996, pp. 1167-1171
Rabbit tibialis anterior muscles were stimulated continuously at 10 Hz
for periods ranging from 2 min to 96 h and were analyzed for energy r
eserves and metabolic intermediates. Glycogen, ATP, and phosphocreatin
e fell rapidly during the first 5 min of stimulation. Glycogen continu
ed to fall to very low levels, whereas ATP and phosphocreatine rose, r
eaching 70% of control by 1 h, despite ongoing stimulation. After 2 h,
glycogen also increased, regaining control levels in 4 days. Glucose
rose to 4.5 times control in 30 min and still exceeded 2.5 times contr
ol at 24 h. In the first 2 min, glycolytic intermediates, glucose B-ph
osphate (G-6-P), fructose 1,6-bisphosphate, lactate, and pyruvate more
than doubled and then returned to control levels or below. Malate and
3-glycerophosphate rose 600 and 200%, respectively. Both of these com
pounds participate in shuttling reducing equivalents from cytoplasm in
to mitochondria. Citrate and alpha-ketoglutarate underwent much more m
odest changes. Glucose 1,6-bisphosphate (G-1,6-P-2) fell to one-third
of control by 2 h and then rose dramatically at 4 h. At 4 days it was
still twice control. The 6-phosphogluconate (6PG) doubled at 2 min, th
en rose to 12 times control at 2 h, fell somewhat, and peaked at 16 ti
mes control at 24 h. Aspartate and alanine both exhibited a biphasic r
ise in concentration, whereas glutamate fell to 30% in 15 min and rose
slowly after 4 h. The rise in glucose was interpreted to be the conse
quence of rapid glycogenolysis together with inhibition of hexokinase
by G-1,6-P-2 and elevated G-6-P. Paradoxically, glycogen resynthesis a
pparently occurred when the glycogen synthase stimulator, G-6-P, was v
ery low, and the glycolysis stimulator, G-1,6-P-2, was high. Although
G-1,6-P-2 is an inhibitor of 6PG dehydrogenase, the timing of the chan
ges in G-1,6-P-2 and 6PG levels suggests that the accumulation of 6PG
was initiated by some other influence.