Excitation of skeletal muscle is a self-limiting process, due to run-down of Na+, K+ gradients, recoverable by stimulation of the Na+, K+ pumps.

The general working hypothesis of this study was that muscle fatigue and force recovery depend on passive and active fluxes of Na(+) and K(+). This is tested by examining the time-course of excitation-induced fluxes of Na(+) and K(+) during 5-300 sec of 10-60 Hz continuous electrical stimulation in rat extensor digitorum longus (EDL) muscles in vitro and in vivo using (22)Na and flame photometric determination of Na(+) and K(+). 60 sec of 60 Hz stimulation rapidly increases (22)Na influx, during the initial phase (0-15 sec) by 0.53 μmol(sec)(-1)(g wet wt.)(-1), sixfold faster than in the later phase (15-60 sec). These values agree with flame photometric measurements of Na(+) content. The progressive reduction in the rate of excitation-induced Na(+) uptake is likely to reflect gradual loss of excitability due to accumulation of K(+) in the extracellular space and t-tubules leading to depolarization. This is in keeping with the concomitant progressive loss of contractile force previously demonstrated. During electrical stimulation rat muscles rapidly reach high rates of active Na(+), K(+)-transport (in EDL muscles a sevenfold increase and in soleus muscles a 22-fold increase), allowing efficient and selective compensation for the large excitation-induced passive Na(+), K(+)-fluxes demonstrated over the latest decades. The excitation-induced changes in passive fluxes of Na(+) and K(+) are both clearly larger than previously observed. The excitation-induced reduction in [Na(+)]o contributes considerably to the inhibitory effect of elevated [K(+)]o. In conclusion, excitation-induced passive and active Na(+) and K(+) fluxes are important causes of muscle fatigue and force recovery, respectively.