Comparative effects of external monovalent cations on sodium pump activity and ouabain inhibition rates in squid giant axon.

1. A number of external monovalent cations were compared with regard to their effects on Na pump rate and the rate of ouabain inhibition of the pump in squid giant axon. 2. External ions which stimulate active Na efflux (K, Rb, and Cs) were found to decrease the rate at which low concentrations of ouabain inhibit the pump, and those ions which inhibit the pump externally (Na and Li) to increase the rate of inhibition. 3. In Na- and Li-containing solutions, pump rate appeared to be the major factor in determining the rate of ouabain inhibition regardless of whether K, Cs, or Rb was used to stimulate active Na efflux. 4. When choline was substituted for external Na, ouabain inhibition rates were more than twice as rapid when Cs was used as the pump-stimulating cation than when K was activating the pump to a similar level. 5. These results suggest that external monovalent cations modulate ouabain inhibition in squid axon at two classes of sites: pump activation sites, and also separate regulatory sites, whose occupation can significantly increase the rate of ouabain inhibition independent of pump turnover rate.