Changes in atp, phosphocreatine and 16 metabolites in muscle stimulated for up to 96 hours. Salmons, Stanley, Jonathan C. Jarvis, Caroline N. Mayne, Maggie M. Y. Chi, Jill K. Manchester, David B. McDougal, and Oliver H. Lowry. Department of Human Anatomy and Cell Biology and The Muscle Research Centre, University of Liverpool, Liverpool, L69 3BX, United Kingdom; and Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO, USA
APStracts 3:0142C, 1996.
Rabbit tibialis anterior muscles were stimulated continuously at 10 Hz for periods ranging from 2 min to 96 hrs and 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 hr, despite ongoing stimulation. After 2 hr 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 hr. In the first 2 min, glycolytic intermediates, glucose-6-phosphate (G6P), fructose 1,6 -bisphosphate, lactate and pyruvate, more than doubled, then returned to or below control levels. Malate and 3-glycero-phosphate 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 bisphosphate (GBP) fell to 1/3rd of control by 2 hr, then rose dramatically at 4 hr. At 4 days it was still twice control. 6 -Phosphogluconate (6PG) doubled at 2 min, then rose to 12 times control at 2 hr, fell somewhat and peaked at 16 times control at 24 hr. Aspartate and alanine both exhibited a biphasic rise in concentration, while glutamate fell to 30% in 15 min and rose slowly after 4 hr. The rise in glucose was interpreted to be the consequence of rapid glycogenolysis together with inhibition of hexokinase by GBP and elevated G6P. Paradoxically, glycogen resynthesis apparently occurred when the glycogen synthetase stimulator, G6P, was very low, and the glycolysis stimulator, GBP, was high. Although GBP is an inhibitor of 6PG dehydrogenase, the timing of the changes in GBP and 6PG levels suggests that the accumulation of 6PG was initiated by some other influence.

Received 21 November 1994; accepted in final form 12 April 1996.
APS Manuscript Number C681-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 May 96