Mechanisms of manganese transport in rabbit erythroid cells.

1. The mechanisms of manganese transport into erythroid cells were investigated using rabbit reticulocytes and mature erythrocytes and 54Mn‐labelled MnCl2 and Mn2‐transferrin. In some experiments iron uptake was also studied. 2. Three saturable manganese transport mechanisms were identified, two for Mn2+ (high and low affinity processes) and one for transferrin‐bound manganese (Mn‐Tf). 3. High affinity Mn2+ transport occurred in reticulocytes but not erythrocytes, was active only in low ionic strength media such as isotonic sucrose and had a Km of 0.4 microM. It was inhibited by metabolic inhibitors and several metal ions. 4. Low affinity Mn2+ transport occurred in erythrocytes as well as in reticulocytes and had Km values of approximately 20 and 50 microM for the two types of cells, respectively. The rate of Mn2+ transport was maximal in isotonic KCl, RbCl or CsCl, and was inhibited by NaCl and by amiloride, valinomycin, diethylstilboestrol and other ion transport inhibitors. The direction of Mn2+ transport was reversible, resulting in Mn2+ efflux from the cells. 5. The uptake of transferrin‐bound manganese occurred only with reticulocytes and depended on receptor‐mediated endocytosis of Mn‐Tf. 6. The characteristics of the three saturable manganese transport mechanisms were similar to corresponding mechanisms of iron uptake by erythroid cells, suggesting that the two metals are transported by the same mechanisms. 7. It is proposed that high affinity manganese transport is a surface representation of the process responsible for the transport of manganese across the endosomal membrane after its release from transferrin. Low affinity transport probably occurs by the previously described Na(+)‐Mg2+ antiport, and may function in the regulation of intracellular manganese concentration by exporting manganese from the cells.

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