The peak force-resting membrane potential relationships of mouse fast- and slow-twitch muscle

We endeavored to understand the factors determining the peak force-resting membrane potential (E_M) relationships of isolated slow-twitch soleus and fast-twitch extensor digitorum longus (EDL) muscles from mice (25°C), especially in relation to fatigue. Interrelationships between intracellular K⁺ activity ([Formula: see text]), extracellular K⁺ concentration ([K⁺]_o), resting E_M, action potentials, and force were studied. The large resting E_M variation was mainly due to the variability of [Formula: see text]. Action potential overshoot-resting E_M relationships determined at 4 and 8-10 mM [K⁺]_o after short (<5 min) and prolonged (>50 min) depolarization periods revealed a constant overshoot from -90 to -70 mV providing a safety margin. Overshoot decline with depolarization beyond -70 mV was less after short than prolonged depolarization. Inexcitable fibers occurred only with prolonged depolarization. The overshoot decline during action potential trains (2 s) exceeded that during short depolarizations. Concomitant lower extracellular [Na⁺] and raised [K⁺]_o depressed the overshoot in an additive manner and peak force in a synergistic manner. Raised [K⁺]_o-induced force loss was exacerbated with transverse wire versus parallel plate stimulation in soleus, implicating action potential propagation failure in the surface membrane. Increasing stimulus pulse parameters restored tetanic force at 9-10 mM [K⁺]_o in soleus but not EDL, indicative of action potential failure within trains. The peak tetanic force-resting E_M relationships (determined with resting E_M from deeper rather than surface fibers) were dynamic and showed pronounced force depression over -69 to -60 mV in both muscle types, implicating that such depolarization contributes to fatigue. The K⁺-Na⁺ interaction shifted this relationship toward less depolarized potentials, suggesting that the combined ionic effect is physiologically important during fatigue.