The effects of Al3+, Cd2+ and Mn2+ on human erythrocyte choline transport

The effects of Al3+, Cd2+ and Mn2+ on human erythrocyte choline transport, Na-K-ATPase, Ca-Mg-ATPase and intracellular K+ levels were examined. The concentrations used were below the levels which caused significant haemolysis (less than or equal to 300 microM). All three cations inhibited concentrative choline accumulation over 3 hr [IC50 values at 1 microM choline were 35 microM (AlCl3), 250 microM (CdCl2) and 300 microM (MnCl2)] but at the concentrations tested, none decreased initial rates of choline uptake. The effects of Cd2+ and Mn2+ (but not Al3+) on choline accumulation were reversed by removing the cations from the extracellular medium by washing. All three cations also inhibited efflux of choline, at 1 microM choline, 30% inhibition being produced by 33 microM AlCl3, 81 microM CdCl2 and 111 microM MnCl2. At subhaemolytic concentrations, only CdCl2 inhibited Na-K-ATPase, (IC50 = 147 microM) and none of the cations significantly inhibited Ca-Mg-ATPase. Intracellular K+ levels were only reduced by the highest concentration of AlCl3 used (100 microM). These results suggest that inhibition of choline accumulation and efflux in erythrocytes by Al3+, Cd2+ and Mn2+ is not explicable solely in terms of either inhibition of Ca-Mg-ATPase, or inhibition of Na-K-ATPase causing reduced intracellular K+. Our conclusions are similar to those previously obtained using synaptosomes and provide support for the hypothesis that inhibition of choline transport by Al3+ may contribute to a number of disease states.