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

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.

Properties of slow- and fast-twitch skeletal muscle from mice with an inherited capacity for hypoxic exercise.

Muscle fiber type, myosin heavy chain (MHC) isoform composition, capillary density (CD) and citrate synthase (CS) activity were investigated in predominantly slow-twitch (soleus or SOL) and fast-twitch (extensor digitorum longus or EDL) skeletal muscle from mice with inherited differences in hypoxic exercise tolerance. Striking differences in hypoxic exercise tolerance previously have been found in two inbred strains of mice, Balb/cByJ (C) and C57BL/6J (B6), and their F1 hybrid following exposure to hypobaric hypoxia. Mice from the three strains were exposed for 8 weeks to either normobaric normoxia or hypobaric hypoxia (1/2 atm). Hypoxia exposure led to a slightly higher 2b fiber composition and a lower fiber area of types 1 and 2a in SOL of all mice. In the EDL, muscle fiber and MHC isoform composition remained unaffected by chronic hypoxia. Chronic hypoxia did not significantly affect CD in either muscle from any of the three strains. There were relatively larger differences in CS activity among strains and treatment, and in SOL the highest CS activity was found in the F1 mice that had been acclimated to hypoxia. In general, however, neither differences among strains nor treatment in these properties of muscle vary in a way that clearly relates to inherited hypoxic exercise tolerance.