Volume-stimulated, Cl(-)-dependent K+ efflux is highly expressed in young human red cells containing normal hemoglobin or HbS.

We report here that a Cl(-)-dependent K+ (K:Cl) efflux, which is stimulated by N-ethylmaleimide (NEM) and by increased red cell volume, exists in young red cells of individuals with normal hemoglobin A (AA) and in those homozygous for hemoglobin S (SS). We have investigated this K:Cl efflux in several density-defined red cell fractions obtained from Percoll-Stractan continuous density gradients. We found high activity of the NEM-stimulated K:Cl transport in reticulocytes and young red cells from nine sickle cell (SS) patients (43 +/- 27 mean +/- SD mmol K+/liter of cells/hr = flux units (FU)) and in the young cell fraction of three AA individuals with high reticulocytosis recuperating from nutritional anemias (41.7 +/- 10 FU). In addition, we observed significant interindividual variation of this K:Cl efflux in the discocyte fraction of SS blood. Cell swelling markedly stimulated the K:Cl efflux, in SS whole blood (9.8 +/- 7.4 FU, in SS young cells (13 +/- 13 FU), and in AA young cells (21.4 +/- 11 FU). The activity of the Na-K-Cl cotransport, as estimated by the bumetanide sensitive K+ efflux was not found to be cell-age dependent in either AA or SS cells. Measurements of red cell density by isopycnic gradients indicated that 27% of the young cells reduce their volume by a Cl(-)-dependent process in hypotonic or low pH-induced swelling. The large volume-stimulated K:Cl efflux in AA young cells raises the possibility that these fluxes may be involved in the maturation of erythropoietic precursors.(ABSTRACT TRUNCATED AT 250 WORDS)