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.

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 H2 0, 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, [3 H]-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, [3 H]-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.