Changes in membrane and surface potential explain the opposite effects of low ionic strength on the two lysine transporters of human erythrocytes.

The sucrose-induced stimulation of lysine influx in human erythrocytes has been attributed to the removal of a competitive inhibition exerted by Na+ on system y+ (Young, J. D., Fincham, D. A., and Harvey, C. M. (1991) Biochim. Biophys. Acta 1070, 111-118). We have reexamined this phenomenon separating the contribution of the two cationic amino acid transporters present in these cells (system y+ and system y+L). NaCl replacement with sucrose increased influx through system y+L, but decreased influx through system y+. We conclude that 1) the inhibition of system y+ is a response to the membrane depolarization that results from chloride removal, and 2) the stimulation of system y+L is due to the enhancement of the negative surface potential. Consistently, lysine influx through system y+L (in sucrose medium) was reduced by Na+, K+, Li+, and choline (K0.5 = 25-34 mM), the effect reaching a maximum at 35-40% of the original flux. Divalent cations (Ca2+ and Mg2+) were also inhibitory, but lower concentrations were required (K0.5 1.1-1.8 mM). The finding that sucrose stimulates uptake through changes in the surface potential explains similar effects observed in other cells with various cationic substrates.