Membrane excitability is a critical regulatory step in skeletal muscle contraction and
is modulated by local ionic concentrations, conductances, ion transporter activities,
temperature, and humoral factors. Intense fatiguing contractions induce cellular K
efflux and Na and Cl influx, causing pronounced perturbations in extracellular
(interstitial) and intracellular K and Na concentrations. Muscle interstitial K
concentration may increase 1- to 2-fold to 11–13 mM and intracellular K
concentration fall by 1.3- to 1.7-fold; interstitial Na concentration may decline by
10 mM and intracellular Na concentration rise by 1.5- to 2.0-fold. Muscle Cl
concentration changes reported with muscle contractions are less consistent, with
reports of both unchanged and increased intracellular Cl concentrations, depending
on contraction type and the muscles studied. When considered together, these
ionic changes depolarize sarcolemmal and t-tubular membranes to depress tetanic
force and are thus likely to contribute to fatigue. Interestingly, less severe local
ionic changes can also augment subtetanic force, suggesting that they may potentiate
muscle contractility early in exercise. Increased Na-K-ATPase activity
during exercise stabilizes Na and K concentration gradients and membrane
excitability and thus protects against fatigue. However, during intense contraction
some Na-K pumps are inactivated and together with further ionic disturbances,
likely precipitate muscle fatigue.