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 (K-0.5 = 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 (K-0.5 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.