High‐frequency fatigue in rat skeletal muscle: Role of extracellular ion concentrations

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Abstract
High-frequency fatigue (HFF), the decline of force during continuous tetanic stimulation (lasting 4–40 s), was studied in isolated bundles of rat skeletal muscle fibers. HFF was slower in slow-twitch soleus fibers than in fast-twitch red or white sternomastoid fibers; denervation accelerated fatigue in soleus. Maximal 200-mmol/L potassium contractures of normal amplitude were induced in fatigued fibers, suggesting that crossbridge cycling and the voltage activation of excitation–contraction coupling could still occur maximally, but that activation by action potentials was impaired. An increase in [Na+]o slowed HFF, while a small increase in [K+]o or reduction in [Cl−]o accelerated HFF. Increasing the tetanic stimulation frequency exacerbated fatigue. Recovery from HFF proceeded rapidly since force increased markedly within a few seconds when stimulation ceased. These results support the hypothesis that a redistribution of Na+, K+, and Cl− across the transverse tubular membranes during repeated action potential activity induces fatigue by reducing the amplitude and conduction of action potentials. © 1995 John Wiley & Sons, Inc.