The effect of sodium pump blockade and denervation on the steady-state sodium permeability of mouse skeletal muscle fibres.

The Na+ pump inhibitor ouabain produced a 25 mV depolarization of mouse extensor digitorum longus muscle fibres in 2 h. Approximately 40% of this depolarization could be prevented by the inclusion of tetrodotoxin (TTX) in the incubation fluid, and the membrane potential of ouabain-depolarized fibres increased when external Na+ ion concentration was reduced. TTX and Na+ reduction were without effect on fibres incubated for 2 h in the control saline or on fibres depolarized by raising external K+ ion concentration. Ouabain induced a fall in input resistance in fibres of reduced chloride conductance. Part of the depolarization induced in the majority of fibres by K+-free solutions was also TTX sensitive. These results suggest that the steady-state Na+ permeability of muscle fibres is increased after Na+ pump blockade. The ouabain-induced depolarization of skeletal muscle therefore cannot be taken as evidence for a significant contribution of an electrogenic Na+ pump to the resting membrane potential. TTX also reverses much of the depolarization which occurs after denervation of skeletal muscle. Denervation and ouabain both increase the steady-state Na+ permeability of the sarcolemma, possibly by an action on the same population of Na+ channels.