An analysis of the influence of membrane potential and metabolic poisoning with azide on the sodium pump in skeletal muscle.

1. Activation of the Na pump in muscle by the external K concentration, [K]O, is independent of the membrane potential (Em) as shown by experiments in which Em was either stabilized during variation of [K]O or varied by application of azide at constant or zero [K]O. 2. Application of azide to Na-enriched muscles causes a transient increase in 22Na efflux which occurs either in the presence or in the absence of external K. 3. The increased 22Na efflux induced by azide is abolished by addition of ouabain and is greatly reduced by removal of almost all of the external Na concentration, [Na]o. 4. Azide-treated muscles show a rather normal K sensitivity of 22Na efflux and [K]O induces a net Na extrusion from Na-enriched muscles in the presence of azide. 5. Azide reduces ouabain-sensitive K influx to low values thus interfering with K pump but not with the ability of K to activate the Na pump. 6. The experiments provide evidence that azide promotes a ouabainsensitive Na-Na exchange in Na-enriched muscles and that it partially uncouples the Na-K exchange normally observed.