The squid giant axon was internally dialyzed while the unidirectional fluxes of either Cl or Na were measured. The effects of varying the internal or external concentration of either Na or Cl were studied. Chloride influx was directly proportional to the external Na concentration whereas Cl efflux was unaffected by changes of the external Na concentration between 0 and 425 mM. Neither Cl influx nor efflux were affected by changes of internal Na concentration over the range of 8-158 mM. After ouabain and TTX treatment a portion of the remaining Na influx was directly dependent on the extracellular Cl concentration. Furthermore, when the internal Cl concentration was increased from 0 to 150 mM, the influxes of Cl and Na were decreased by 14 and 11 pmol/cm2.s, respectively. The influx of both ions could be substantially reduced when the axon was depleted of ATP. The influxes of both ions were inhibited by furosemide but unaffected by ouabain. It is concluded that the squid axolemma has an ATP-dependent coupled Na-Cl co-transport uptake mechanism.

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