Skip to main content
Log in

Interspersed normoxia during live high, train low interventions reverses an early reduction in muscle Na+, K+ATPase activity in well-trained athletes

  • Original Article
  • Published:
European Journal of Applied Physiology Aims and scope Submit manuscript

Abstract

Hypoxia and exercise each modulate muscle Na+, K+ATPase activity. We investigated the effects on muscle Na+, K+ATPase activity of only 5 nights of live high, train low hypoxia (LHTL), 20 nights consecutive (LHTLc) versus intermittent LHTL (LHTLi), and acute sprint exercise. Thirty-three athletes were assigned to control (CON, n = 11), 20-nights LHTLc (n = 12) or 20-nights LHTLi (4 × 5-nights LHTL interspersed with 2-nights CON, n = 10) groups. LHTLc and LHTLi slept at a simulated altitude of 2,650 m (FIO2 0.1627) and lived and trained by day under normoxic conditions; CON lived, trained, and slept in normoxia. A quadriceps muscle biopsy was taken at rest and immediately after standardised sprint exercise, before (Pre) and after 5-nights (d5) and 20-nights (Post) LHTL interventions and analysed for Na+, K+ATPase maximal activity (3-O-MFPase) and content ([3H]-ouabain binding). After only 5-nights LHTLc, muscle 3-O-MFPase activity declined by 2% (< 0.05). In LHTLc, 3-O-MFPase activity remained below Pre after 20 nights. In contrast, in LHTLi, this small initial decrease was reversed after 20 nights, with restoration of 3-O-MFPase activity to Pre-intervention levels. Plasma [K+] was unaltered by any LHTL. After acute sprint exercise 3-O-MFPase activity was reduced (12.9 ± 4.0%, < 0.05), but [3H]-ouabain binding was unchanged. In conclusion, maximal Na+, K+ATPase activity declined after only 5-nights LHTL, but the inclusion of additional interspersed normoxic nights reversed this effect, despite athletes receiving the same amount of hypoxic exposure. There were no effects of consecutive or intermittent nightly LHTL on the acute decrease in Na+, K+ATPase activity with sprint exercise effects or on plasma [K+] during exercise.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Aughey RJ, Gore CJ, Hahn AG, Garnham AP, Clark SA, Petersen AC, Roberts AD, McKenna MJ (2005) Chronic intermittent hypoxia and incremental cycling exercise independently depress muscle in-vitro maximal Na+, K+ATPase activity in well-trained athletes. J Appl Physiol 98:186–192

    Article  PubMed  CAS  Google Scholar 

  • Blanco G, Mercer RW (1998) Isozymes of the Na-K-ATPase: heterogeneity in structure: diversity in function. Am J Physiol Renal Physiol 275:F633–F1268

    CAS  Google Scholar 

  • Brugniaux JV, Schmitt L, Robach P, Nicolet G, Fouillot JP, Moutereau S, Lasne F, Pialoux V, Saas P, Chorvot MC, Cornolo J, Olsen NV, Richalet JP (2006) Eighteen days of “living high, training low” stimulate erythropoiesis and enhance aerobic performance in elite middle-distance runners. J Appl Physiol 100:203–211

    Article  PubMed  Google Scholar 

  • Clark SA, Aughey RJ, Gore CJ, Hahn AG, Townsend NE, Kinsman TA, Chow C-M, McKenna MJ, Hawley JA (2004) Effects of live high, train low hypoxic exposure on lactate metabolism in trained humans. J Appl Physiol 96:517–525

    Article  PubMed  Google Scholar 

  • Clausen T (2003) Na+–K+ pump regulation and skeletal muscle contractility. Physiol Rev 83:1269–1324

    PubMed  CAS  Google Scholar 

  • Clausen T, Everts ME (1989) Regulation of the Na, K-pump in skeletal muscle. Kidney Int 35:1–13

    Article  PubMed  CAS  Google Scholar 

  • Clausen T, Andersen SL, Flatman JA (1993) Na+–K+ pump stimulation elicits recovery of contractility in K+-paralysed rat muscle. J Physiol 472:521–536

    PubMed  CAS  Google Scholar 

  • Clausen T, Overgaard K, Nielsen OB (2004) Evidence that the Na+–K+ leak/pump ratio contributes to the difference in endurance between fast- and slow-twitch muscles. Acta Physiol Scand 180:209–216

    Article  PubMed  CAS  Google Scholar 

  • Evertsen F, Medbø JI, Jebens E, Nicolaysen K (1997) Hard training for 5 mo increases Na+–K+ pump concentration in skeletal muscle of cross-country skiers. Am J Physiol Regul Integr Comp Physiol 272:R1417–R1424

    CAS  Google Scholar 

  • Forster HV, Dempsey JA, Thomson J, Vidruk E, doPico GA (1972) Estimation of arterial pO2, pCO2, pH and lactate from arterialized venous blood. J Appl Physiol 32:134–137

    PubMed  CAS  Google Scholar 

  • Fowles JR, Green HJ, Tupling R, O’Brien S, Roy BD (2002) Human neuromuscular fatigue is associated with altered Na+-K+-ATPase activity following isometric exercise. J Appl Physiol 92:1585–1593

    PubMed  CAS  Google Scholar 

  • Fraser SF, McKenna MJ (1998) Measurement of Na+, K+-ATPase activity in human skeletal muscle. Anal Biochem 258:63–67

    Article  PubMed  CAS  Google Scholar 

  • Fraser SF, Li JL, Carey MF, Wang XN, Sangkabutra T, Sostaric S, Selig SE, Kjeldsen K, McKenna MJ (2002) Fatigue depresses maximal in vitro skeletal muscle Na+-K+-ATPase activity in untrained and trained individuals. J Appl Physiol 93:1650–1659

    PubMed  CAS  Google Scholar 

  • Green HJ, Chin ER, Ball-Burnett M, Ranney D (1993) Increases in human skeletal muscle Na+-K+-ATPase concentration with short-term training. Am J Physiol 264:C1538–C1541

    PubMed  CAS  Google Scholar 

  • Green H, Dahly A, Shoemaker K, Goreham C, Bombardier E, Ball-Burnett M (1999a) Serial effects of high-resistance and prolonged endurance training on Na+–K+ pump concentration and enzymatic activities in human vastus lateralis. Acta Physiol Scand 165:177–184

    Article  CAS  Google Scholar 

  • Green H, MacDougall J, Tarnopolsky M, Melissa NL (1999b) Downregulation of Na+–K+ATPase pumps in skeletal muscle with training in normobaric hypoxia. J Appl Physiol 86:1745–1748

    CAS  Google Scholar 

  • Green S, Bulow J, Saltin B (1999c) Microdialysis and the measurement of muscle interstitial K+ during rest and exercise in humans. J Appl Physiol 87:460–464

    CAS  Google Scholar 

  • Green H, Roy B, Grant S, Burnett M, Tupling R, Otto C, Pipe A, McKenzie D (2000) Downregulation in muscle Na+-K+ATPase following a 21 day expedition to 6194m. J Appl Physiol 88:634–640

    PubMed  CAS  Google Scholar 

  • Green HJ, Barr DJ, Fowles JR, Sandiford SD, Ouyang J (2004) Malleability of human skeletal muscle Na+-K+-ATPase pump with short-term training. J Appl Physiol 97:143–148

    Article  PubMed  CAS  Google Scholar 

  • Hahn AG, Gore CJ (2001) The effect of altitude on cycling performance: a challenge to traditional concepts. Sports Med 31:533–557

    Article  PubMed  CAS  Google Scholar 

  • Hahn AG, Gore CJ, Martin DT, Ashenden MJ, Roberts AD, Logan PA (2001) An evaluation of the concept of living at moderate altitude and training at sea level. Comp Biochem Physiol A Mol Integr Physiol 128:777–789

    Article  PubMed  CAS  Google Scholar 

  • Harmer AR, McKenna MJ, Sutton JR, Snow RJ, Ruell PA, Booth J, Thompson MW, Mackay NA, Stathis CG, Crameri RM, Carey MF, Eager DM (2000) Skeletal muscle metabolic and ionic adaptations during intense exercise following sprint training in humans. J Appl Physiol 89:1763–1803

    Google Scholar 

  • Hawley JA, Myburgh KH, Noakes TD, Dennis SC (1997) Training techniques to improve fatigue resistance and enhance endurance performance. J Sports Sci 15:325–333

    Article  PubMed  CAS  Google Scholar 

  • Huck SW, McLean R (1975) Using a repeated measures ANOVA to analyze the data from a pretest–posttest design: a potentially confusing task. Psychol Bull 82:511–518

    Article  Google Scholar 

  • Juel C (2001) Measurement of interstitial K+ in exercising human skeletal muscle using the microdialysis technique. In: Pumps, channels and their physiological significance. Scandinavian Physiological Society, University of Aarhus, Denmark

  • Klitgaard H, Clausen T (1989) Increased total concentration of Na–K pumps in vastus lateralis muscle of old trained human subjects. J Appl Physiol 67:2491–2494

    PubMed  CAS  Google Scholar 

  • Leivseth G, Clausen T, Everts ME, Bjordal E (1992) Effects of reduced joint mobility and training on Na+, K+-ATPase and Ca2+-ATPase in skeletal muscle. Muscle Nerve 15:843–849

    Article  PubMed  CAS  Google Scholar 

  • Levine BD, Stray-Gundersen J (1992) A practical approach to altitude training: where to live and train for optimal training enhancement. Int J Sports Med 13:s209–S212

    Article  PubMed  Google Scholar 

  • Levine BD, Stray-Gundersen J (1997) “Living high–training low”: effect of moderate-altitude acclimatization with low-altitude training on performance. J Appl Physiol 83:102–112

    PubMed  CAS  Google Scholar 

  • Levine BD, Friedman B, Stray-Gundersen J (1996) Confirmation of the “high–low” hypothesis: living at altitude–training near sea level improves sea level performance. Med Sci Sports Exerc 28

  • Lowry OH, Rosenbrough NJ, Farr AL, Rankin J (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193:265–275

    PubMed  CAS  Google Scholar 

  • Madsen K, Franch J, Clausen T (1994) Effects of intensified endurance training on the concentration of Na+, K+-ATPase and Ca2+-ATPase in human skeletal muscle. Acta Physiol Scand 150:251–258

    PubMed  CAS  Google Scholar 

  • McKenna MJ, Schmidt TA, Hargreaves M, Cameron L, Skinner SL, Kjeldsen K (1993) Sprint training increases human skeletal muscle Na+-K+-ATPase concentration and improves K+ regulation. J Appl Physiol 75:173–180

    PubMed  CAS  Google Scholar 

  • McKenna MJ, Heigenhauser GJF, McKelvie RS, MacDougall JD, Jones NL (1997) Sprint training enhances ionic regulation during intense exercise in man. J Physiol (Lond) 501:687–702

    Article  CAS  Google Scholar 

  • McLoughlin P, Popham P, Linton AF, Bruce RCH, Band DM (1992) Use of arterialized venous blood sampling during incremental exercise. J Appl Physiol 73:937–940

    PubMed  CAS  Google Scholar 

  • Medbø JI, Jebens E, Vikne H, Refsnes PE, Gramvik P (2001) Effect of strenuous strength training on the Na+–K+ pump concentration in skeletal muscle of well-trained men. Eur J Appl Physiol 84:148–154

    Article  PubMed  Google Scholar 

  • Mohr M, Nordsborg N, Nielsen JJ, Pedersen LD, Fischer C, Krustrup P, Bangsbo J (2004) Potassium kinetics in human muscle interstitium during repeated intense exercise in relation to fatigue. Pflugers Arch 448:452–456

    Article  PubMed  CAS  Google Scholar 

  • Murphy KT, Snow RJ, Petersen AC, Murphy RM, Mollica J, Lee JS, Garnham AP, Aughey RJ, Leppik JA, Medved I, Cameron-Smith D, McKenna MJ (2004) Intense exercise up-regulates Na+, K+-ATPase isoform mRNA, but not protein expression in human skeletal muscle. J Physiol (Lond) 556:507–519

    Article  CAS  Google Scholar 

  • Murphy KT, Macdonald WA, McKenna MJ, Clausen T (2005) Ionic mechanisms of excitation-induced regulation of Na+, K+-ATPase mRNA expression in isolated rat EDL muscle. Am J Physiol Regul Integr Comp Physiol

  • Nielsen OB, Clausen T (2000) The Na+/K+-pump protects muscle excitability and contractility during exercise. Exerc Sports Sci Rev 28:159–164

    CAS  Google Scholar 

  • Nordsborg N, Mohr M, Pedersen LD, Nielsen JJ, Langberg H, Bangsbo J (2003) Muscle interstitial potassium kinetics during intense exhaustive exercise: effect of previous arm exercise. Am J Physiol Regul Integr Comp Physiol 285:R143–R148

    PubMed  CAS  Google Scholar 

  • Nordsborg N, Thomassen M, Lundby C, Pilegaard H, Bangsbo J (2005) Contraction induced increases in Na+, K+-ATPase mRNA levels in human skeletal muscle are not amplified by activation of additional muscle mass. Am J Physiol Regul Integr Comp Physiol, 00771.02004

  • Nørgaard A, Kjeldsen K, Clausen T (1984) A method for the determination of the total number of [3H]ouabain binding sites in biopsies of human skeletal muscle. Scand J Clin Lab Investig 44:509–518

    Article  Google Scholar 

  • Nummela A, Rusko H (2000) Acclimatisation to altitude and normoxic training improve 400 m running performance at sea-level. J Sports Sci 18:411–419

    Article  PubMed  CAS  Google Scholar 

  • Overgaard K, Nielsen OB, Flatman JA, Clausen T (1999) Relations between excitability and contractility in rat soleus muscle: role of the Na+K+ pump and Na+/K+ gradients. J Physiol (Lond) 518:215–225

    Article  CAS  Google Scholar 

  • Petersen AC, Murphy KT, Snow RJ, Leppik JA, Aughey RJ, Garnham AP, Cameron-Smith D, McKenna MJ (2005) Depressed Na+, K+-ATPase activity in skeletal muscle is correlated with increased Na+, K+-ATPase mRNA expression following intense exercise. Am J Physiol Regul Integr Comp Physiol, 00378.02004

  • Roberts AD, Clark SA, Townsend NE, Anderson ME, Gore CJ, Hahn AG (2003) Changes in performance, maximal oxygen uptake and maximal accumulated oxygen deficit after 5, 10 and 15 days of live high:train low altitude exposure. Eur J Appl Physiol 88:390–395

    Article  PubMed  CAS  Google Scholar 

  • Sandiford SD, Green HJ, Duhamel TA, Perco JG, Schertzer JD, Ouyang J (2004) Inactivation of human muscle Na+-K+-ATPase in vitro during prolonged exercise is increased with hypoxia. J Appl Physiol 96:1767–1775

    Article  PubMed  CAS  Google Scholar 

  • Saunders PU, Telford RD, Pyne DB, Cunningham RB, Gore CJ, Hahn AG, Hawley JA (2004) Improved running economy in elite runners after 20 days of simulated moderate-altitude exposure. J Appl Physiol 96:931–937

    Article  PubMed  CAS  Google Scholar 

  • Sejersted OM, Sjøgaard G (2000) Dynamics and consequences of potassium shifts in skeletal muscle and heart during exercise. Physiol Rev 80:1411–1481

    PubMed  CAS  Google Scholar 

  • Sjøgaard G, Adams RP, Saltin B (1985) Water and ion shifts in skeletal muscle of humans with intense dynamic knee extension. Am J Physiol 248:R190–R196

    PubMed  Google Scholar 

  • Stray-Gundersen J, Levine BJ (1999) “Living high and training low” can improve sea-level performance in endurance athletes. Br J Sports Med 33:150–151

    PubMed  CAS  Google Scholar 

  • Stray-Gundersen J, Chapman RF, Levine BD (2001) “Living high–training low” altitude training improves sea level performance in male and female elite runners. J Appl Physiol 91:1113–1120

    PubMed  CAS  Google Scholar 

  • Street D, Nielsen JJ, Bangsbo J, Juel C (2005) Metabolic alkalosis reduces exercise-induced acidosis and potassium accumulation in human skeletal muscle interstitium. J Physiol 566:481–489

    Article  PubMed  CAS  Google Scholar 

  • Townsend NE, Gore CJ, Hahn AG, McKenna MJ, Aughey RJ, Clark SA, Kinsman T, Hawley JA, Chow C-M (2002) Living high–training low increases hypoxic ventilatory response of well-trained endurance athletes. J Appl Physiol 93:1498–1505

    PubMed  Google Scholar 

Download references

Acknowledgments

We thank our participants for their generous involvement in this lengthy and demanding study. We also thank Dr. Andrew Garnham and Dr. Kieran Fallon for collection of muscle biopsy samples and the staff of the Department of Physiology, Australian Institute of Sport, for invaluable technical assistance. This study was funded by an Australian Research Council Grant C00002552, and in part by NH&MRC of Australia Grant 256603.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M. J. McKenna.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Aughey, R.J., Clark, S.A., Gore, C.J. et al. Interspersed normoxia during live high, train low interventions reverses an early reduction in muscle Na+, K+ATPase activity in well-trained athletes. Eur J Appl Physiol 98, 299–309 (2006). https://doi.org/10.1007/s00421-006-0280-z

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00421-006-0280-z

Keywords

Navigation