Changes of action potentials and force at lowered [Na+]o in mouse skeletal muscle:: implications for fatigue

We examined 1) whether the effects of lowered trans-sarcolemmal Na+ gradient on force differed between nonfatigued fast- and slow-twitch muscles of mice and 2) whether effects on action potentials could explain the decrease of force. The Na+ gradient was reduced by lowering the extracellular [Na+] ([Na+](o)). The peak force-[Na+](o) relationships for the twitch and tetanus were the same in nonfatigued extensor digitorum longus and soleus muscles: force was maintained over a large range of [Na+](o) and then decreased abruptly over a much smaller range. However, fatigue was significantly exacerbated at a lowered [Na+](o) that had little effect in nonfatigued soleus muscle. This finding suggests that substantial differences exist in the Na+ effect on force between nonfatigued and fatigued muscle. The reduced contractility in nonfatigued muscles at lowered [Na+](o) was largely due to 1) an increased number of inexcitable fibers and threshold for action potentials, 2) a reduction of action potential amplitude, and 3) a reduced capacity to generate action potentials throughout trains.