Na+ modulates carrier-mediated Fe2+ transport through the erythroid cell membrane

The effects of univalent cations on Fe2+ uptake by rabbit reticulocytes have been studied. The rate of Fe2+ uptake was almost identical when measured in Na(+)-free choline chloride or KCl medium. Na+ but not Li+ inhibited Fe2+ uptake even at relatively low concentrations (2.5-20 mM) in these media. In contrast to this effect of extracellular Na+, the rate of Fe2+ uptake was facilitated by an increase in the intracellular Na2+ concentration in the range 5-40 mM, suggesting that intracellular Na+ is required for the uptake process. This effect also appears to be specific for Na+. Amiloride inhibited Fe2+ uptake in KCl (or in choline chloride), but had little if any effect in NaCl. Therefore a Na(+)- and amiloride-sensitive and a Na(+)- and amiloride-insensitive component can be distinguished. The two components differ in maximum velocity and pH optimum, but not in their apparent affinity for Fe2+. The ineffectiveness of selective inhibitors excludes the involvement of the Na+/H+ or Na+/Ca2+ exchange mechanisms. To account for the results presented in this work, a Na+/Fe2+ exchange system in the erythroid cell membrane is proposed.