Inhibition of K transport by divalent cations in sickle erythrocytes

We report experiments on the effect of intracellular divalent cations (Mg, Ca, Mn) on K transport and cell volume in erythrocytes from patients with homozygous hemoglobin S disease (SS cells). When CO- treated SS erythrocytes are exposed to the ionophore A23187, removal of cell Mg markedly stimulates K efflux, whereas increasing cell Mg inhibits K efflux. The Ki for the inhibition by internal free Mg is 0.38 +/- 0.10 mmol/L, a value comparable to the concentration of free Mg in normal cells (0.3 to 0.4 mmol/L). When swollen SS cells with increased Mg content were incubated in plasma-like medium, they shrunk much less than swollen SS cells with normal Mg content. Thus, elevation of cell Mg produces inhibition of swelling-induced K movement from SS cells. Internal Ca and Mn also inhibit K movement from SS cells. The inhibition of volume regulation by divalent cations suggests that increases in intracellular divalent ions, especially Mg, could induce a persistent degree of cell swelling in SS RBCs and thereby inhibit intracellular polymerization.