A century of exercise physiology: effects of muscle contraction and exercise on skeletal muscle Na+,K+-ATPase, Na+ and K+ ions, and on plasma K+ concentration—historical developments

Michael J. McKenna*, Jean Marc Renaud, Niels Ørtenblad, Kristian Overgaard

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperReviewResearchpeer-review

Abstract

This historical review traces key discoveries regarding K+ and Na+ ions in skeletal muscle at rest and with exercise, including contents and concentrations, Na+,K+-ATPase (NKA) and exercise effects on plasma [K+] in humans. Following initial measures in 1896 of muscle contents in various species, including humans, electrical stimulation of animal muscle showed K+ loss and gains in Na+, Cl and H20, then subsequently bidirectional muscle K+ and Na+ fluxes. After NKA discovery in 1957, methods were developed to quantify muscle NKA activity via rates of ATP hydrolysis, Na+/K+ radioisotope fluxes, [3H]-ouabain binding and phosphatase activity. Since then, it became clear that NKA plays a central role in Na+/K+ homeostasis and that NKA content and activity are regulated by muscle contractions and numerous hormones. During intense exercise in humans, muscle intracellular [K+] falls by 21 mM (range − 13 to − 39 mM), interstitial [K+] increases to 12–13 mM, and plasma [K+] rises to 6–8 mM, whilst post-exercise plasma [K+] falls rapidly, reflecting increased muscle NKA activity. Contractions were shown to increase NKA activity in proportion to activation frequency in animal intact muscle preparations. In human muscle, [3H]-ouabain-binding content fully quantifies NKA content, whilst the method mainly detects α2 isoforms in rats. Acute or chronic exercise affects human muscle K+, NKA content, activity, isoforms and phospholemman (FXYD1). Numerous hormones, pharmacological and dietary interventions, altered acid–base or redox states, exercise training and physical inactivity modulate plasma [K+] during exercise. Finally, historical research approaches largely excluded female participants and typically used very small sample sizes.

Original languageEnglish
JournalEuropean Journal of Applied Physiology
Volume124
Issue3
Pages (from-to)681-751
Number of pages71
ISSN1439-6319
DOIs
Publication statusPublished - Mar 2024

Keywords

  • Exercise
  • Fatigue
  • FXYD
  • Na, K-pump
  • Plasma
  • Potassium
  • Skeletal muscle
  • Sodium

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