The role of anion transport in the passive movement of lead across the human red cell membrane.

Passive Pb transport across the red cell membrane has been studied by measuring Pb uptake from Pb-buffered solutions into resealed ghosts containing EGTA. Over 90% of Pb uptake occurs by a pathway which is inhibited by drugs which block anion transport. The order of effectiveness is 4,4'-diisothiocyanostilbene-2,2'-disulphonic acid (DIDS) and 4-acetamido-4'-isothiocyanostilbene-2,2'-disulphonic acid (SITS) greater than phloretin greater than furosemide and bumetanide. Ouabain and cytochalasin B are ineffective. This implicates the anion-exchange mechanism in Pb uptake. The rate of Pb uptake by this route is directly proportional to external Pb2+ and HCO3- concentrations, and inversely proportional to the H+ concentration. These findings suggest that Pb transport depends on the formation of PbCO3 in solution. Pb transport depends upon the presence of a second anion. In the presence of HCO3-, the rate is stimulated in the order ClO4- less than NO3- and CH3CO2- less than F- less than Cl- less than Br- less than I-. The temperature dependence of Pb uptake is similar to that of HCO3-(-)Cl- exchange. Changes in membrane potential appear to influence Pb transport. The effects are small and somewhat variable, but in general a negative internal potential accelerates uptake and reduces exit. A positive internal potential reduces uptake and accelerates exit. These results suggest that Pb is transported on the anion exchanger. Exchange of PbCO3 for a monovalent anion best fits the experimental data, although transport of a ternary PbCO3(-)anion- complex is a possibility.