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 extemal 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.