The Uptake of Divalent Manganese Ion by Mature Normal Human Red Blood Cells

At physiological pH and concentrations of Mn(++) in excess of 5 x 10(-4)M, study of the Mn(++) ion movement into human red cells is complicated by physicochemical alterations of the ion itself. At concentrations below 5 x 10(x4)M, the rate of uptake bears a linear relationship to the Mn(++) concentration. The permeability constant for inward movement of Mn(++) is 2.87 +/- 0.13 (S.E.) x 10(-9) cm./sec. The rate is not influenced by the addition of metabolic substrates such as glucose or adenosine or the metabolic inhibitors iodoacetate or fluoride. Co(++), Ca(++), and Mg(++) do not appear to compete with Mn(++) for entry, but at high concentrations relative to Mn(++), they reduce the rate of entry. Ca(++) is far more effective than Co(++) or Mg(++) in this regard. The permeability constant for outward Mn(++) movement is 1.38 +/- 0.21 (S.E.) x 10(-9) cm./sec., about half of that for entry. This slower rate of outward movement is consistent with the finding that 40 to 60 per cent of the Mn(++) taken up by the red cells is non-ultrafilterable. Less than 5 to 10 per cent of the Mn(++) appears to be bound to the stroma. It is concluded that entry and exit of Mn(++) is a process of passive diffusion involving no carriers, transport, or metabolic linkage.