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

摘要

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 ²²Na and flame photometric determination of Na⁺ and K⁺. 60 sec of 60 Hz stimulation rapidly increases ²²Na 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.