High energy phosphate concentrations and AMPK phosphorylation in skeletal muscle from mice with inherited differences in hypoxic exercise tolerance

Comp Biochem Physiol A Mol Integr Physiol. 2009 Apr;152(4):478-85. doi: 10.1016/j.cbpa.2008.11.019. Epub 2008 Dec 6.


The effect of chronic hypobaric hypoxia (1/2 atmospheric pressure) on high energy phosphate (HEP) compounds was investigated in slow (soleus; SOL) and fast twitch (extensor digitorum longus; EDL) muscle from 3 strains of mice with large differences in hypoxic exercise tolerance (HET). Phosphocreatine concentration ([PCr]) decreased 16-29% following hypoxia in EDL and SOL in all strains, while [ADP] and [AMP] increased. In the EDL, HET was negatively correlated with the PCr/ATP ratio and positively correlated with the ATP/P(i) ratio. The free energy of ATP hydrolysis (DeltaG(obs)) remained constant despite the substantial changes that occurred in HEP profiles. The alteration of HEP set points and preservation of DeltaG(obs) are consistent with the notion that (1) maximal rates of steady-state ATP turnover are reduced under hypoxia, and (2) HEP perturbations during rest to work transitions are reduced in skeletal muscle from hypoxia acclimated animals. We therefore expected a lower phosphorylation ratio of AMP-activated protein kinase (AMPK-P/AMPK) during stimulation in hypoxic acclimated animals. However, neither the resting nor stimulated AMPK-P/AMPK was influenced by hypoxia, although there were significant differences among strains.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • Body Mass Index
  • Energy Metabolism*
  • Hypoxia / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Models, Animal
  • Muscle, Skeletal / metabolism*
  • Phosphates / metabolism*
  • Phosphorylation
  • Physical Exertion / physiology*


  • Phosphates
  • AMP-Activated Protein Kinases