Changes in ATP, phosphocreatine, and 16 metabolites in muscle stimulated for up to 96 hours
Salmons, S.; Jarvis, J.C.; Mayne, C.N.; Chi, M.M.; Manchester, J.K.; McDougal, D.B.; Lowry, O.H.
American Journal of Physiology 271(4 Pt 1): C1167-C1171
1996
ISSN/ISBN: 0002-9513 PMID: 8897822 Document Number: 461572
Rabbit tibialis anterior muscles were stimulated continuously at 10 Hz for periods ranging from 2 min to 96 h and were analyzed for energy reserves and metabolic intermediates. Glycogen, ATP, and phosphocreatine fell rapidly during the first 5 min of stimulation. Glycogen continued to fall to very low levels, whereas ATP and phosphocreatine rose, reaching 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 control at 24 h. In the first 2 min, glycolytic intermediates, glucose 6-phosphate (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 compounds participate in shuttling reducing equivalents from cytoplasm into mitochondria. Citrate and alpha-ketoglutarate underwent much more modest 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, then rose to 12 times control at 2 h, fell somewhat, and peaked at 16 times control at 24 h. Aspartate and alanine both exhibited a biphasic rise 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 consequence of rapid glycogenolysis together with inhibition of hexokinase by G-1,6-P-2 and elevated G-6-P. Paradoxically, glycogen resynthesis apparently occurred when the glycogen synthase stimulator, G-6-P, was very 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 changes in G- 1,6-P-2 and 6PG levels suggests that the accumulation of 6PG was initiated by some other influence.