Chronic intermittent hypoxia and incremental cycling exercise independently depress muscle in vitro maximal Na+-K+-ATPase activity in well-trained athletes

Athletes commonly attempt to enhance performance by training in normoxia but sleeping in hypoxia [live high and train low (LHTL)]. However, chronic hypoxia reduces muscle Na⁺-K⁺-ATPase content, whereas fatiguing contractions reduce Na⁺-K⁺-ATPase activity, which each may impair performance. We examined whether LHTL and intense exercise would decrease muscle Na⁺-K⁺-ATPase activity and whether these effects would be additive and sufficient to impair performance or plasma K⁺ regulation. Thirteen subjects were randomly assigned to two fitness-matched groups, LHTL (n = 6) or control (Con, n = 7). LHTL slept at simulated moderate altitude (3,000 m, inspired O₂ fraction = 15.48%) for 23 nights and lived and trained by day under normoxic conditions in Canberra (altitude ~600 m). Con lived, trained, and slept in normoxia. A standardized incremental exercise test was conducted before and after LHTL. A vastus lateralis muscle biopsy was taken at rest and after exercise, before and after LHTL or Con, and analyzed for maximal Na⁺-K⁺-ATPase activity [K⁺-stimulated 3-O-methylfluorescein phosphatase (3-O-MFPase)] and Na⁺-K⁺-ATPase content ([³H]ouabain binding sites). 3-O-MFPase activity was decreased by –2.9 ± 2.6% in LHTL (P < 0.05) and was depressed immediately after exercise (P < 0.05) similarly in Con and LHTL (–13.0 ± 3.2 and –11.8 ± 1.5%, respectively). Plasma K⁺ concentration during exercise was unchanged by LHTL; [3H]ouabain binding was unchanged with LHTL or exercise. Peak oxygen consumption was reduced in LHTL (P < 0.05) but not in Con, whereas exercise work was unchanged in either group. Thus LHTL had a minor effect on, and incremental exercise reduced, Na⁺-K⁺-ATPase activity. However, the small LHTL-induced depression of 3-O-MFPase activity was insufficient to adversely affect either K⁺ regulation or total work performed.

Effect of exercise intensity and hypoxia on skeletal muscle AMPK signaling and substrate metabolism in humans

We compared in human skeletal muscle the effect of absolute vs. relative exercise intensity on AMP-activated protein kinase (AMPK) signaling and substrate metabolism under normoxic and hypoxic conditions. Eight untrained males cycled for 30 min under hypoxic conditions (11.5% O2, 111 ± 12 W, 72 ± 3% hypoxia VO2 peak; 72% Hypoxia) or under normoxic conditions (20.9% O2) matched to the same absolute (111 ± 12 W, 51 ± 1% normoxia VO2 peak; 51% Normoxia) or relative (to VO2 peak) intensity (171 ± 18 W, 73 ± 1% normoxia VO2 peak; 73% Normoxia). Increases (P < 0.05) in AMPK activity, AMPK{alpha} Thr172 phosphorylation, ACCbeta Ser221 phosphorylation, free AMP content, and glucose clearance were more influenced by the absolute than by the relative exercise intensity, being greatest in 73% Normoxia with no difference between 51% Normoxia and 72% Hypoxia. In contrast to this, increases in muscle glycogen use, muscle lactate content, and plasma catecholamine concentration were more influenced by the relative than by the absolute exercise intensity, being similar in 72% Hypoxia and 73% Normoxia, with both trials higher than in 51% Normoxia. In conclusion, increases in muscle AMPK signaling, free AMP content, and glucose disposal during exercise are largely determined by the absolute exercise intensity, whereas increases in plasma catecholamine levels, muscle glycogen use, and muscle lactate levels are more closely associated with the relative exercise intensity.