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 H0, 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, [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, [H]-ouabain-binding content fully quantifies NKA content, whilst the method mainly detects α 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.