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.
Brugnara
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Department of Physiology and Biophysics, Harvard Medical School, Boston, MA 02115.
Tosteson
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DC
D000755:Anemia, Sickle Cell / Q000097:blood*; D001692:Biological Transport; D002413:Cations, Divalent / Q000494:pharmacology; D004913:Erythrocytes, Abnormal / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008274:Magnesium / Q000097:blood*; D011188:Potassium / Q000097:blood*; D014882:Water-Electrolyte Balance
D002413:Cations, Divalent; D008274:Magnesium; D011188:Potassium