The modulation of the calcium pump of human red cells by Na+ and K+

The sidedness of Ca2+-pump activation by Na+ and K+ was studied by atomic absorption spectrophotometry in human erythrocyte ghosts, which had been prepared in dextran solutions and resealed to alkali cations. When ghosts were incubated in an all-choline medium, the increase in Na+i elicited an inhibitory-stimulatory effect on Ca2+ extrusion. By contrast, only a stimulatory action was induced when choline was replaced by Na+o. A dual effect on active Ca2+ efflux was also produced by increasing K+i or K+o. The biphasic response to the latter, however, was absent from high-K+ ghosts. Furthermore, the stimulation obtained at high K+o was additive to that elicited by K+i. The results suggest that Na+ and K+ stimulate the Ca2+ pump of human red cells through two different mechanisms. The first one appears to be an electric coupling between Ca2+ efflux and the external activating cation. The other seems associated with the molecular reactions of the Ca2+-pump protein.