Extracellular cations and the movement of choline across the erythrocyte membrane.

1. The ability of human erythrocytes to accumulate choline is abolished when external Na is replaced by Cs, Rb, K or Li but is increased when the external cation is Mg or Ca.2. The unidirectional influx of choline is reduced when external Na is replaced by other monovalent cations but is not changed when Na is replaced by Mg or Ca.3. The unidirectional efflux of choline into a choline-free medium is increased when external Na is replaced by other monovalent cations and markedly reduced when Na is replaced by Mg or Ca. When the external medium contains 1 mM choline, changing the external cation has virtually no effect on the rate of choline efflux.4. When the extracellular concentrations of K and Na are similar to that found in the intracellular water, choline appears to become passively distributed across the cell membrane; when the extracellular K is then replaced by Cs a net efflux of choline against a concentration gradient results.5. It is concluded that the choline carrier may be described as a cation carrier with a high affinity for choline and affinities for Cs > Rb > K > Li > Na and that these monovalent cations can cross the membrane on the choline transport system.