Effects of AlCl3 on toad skin, human erythrocytes, and model cell membranes

Aluminum, a very abundant metal, could play a toxic role in several pathological processes, including neurodegeneration. Although the effects of Al(III) on biological membranes have been extensively described, direct information concerning the molecular basis of its biological activity is rather scanty. To examine aluminum challenges on cell membranes, various concentrations of AlCl3 in aqueous solutions were incubated with human erythrocytes, isolated toad skin, and molecular models of biomembranes. The latter consisted of multilayers of dimyristoylphosphatidylcholine and dimyristoylphosphatidylethanolamine, representing phospholipid classes located in the outer and inner monolayers of the human erythrocyte membrane. These specimens were studied by scanning electron microscopy, electrophysiological measurements, and x-ray diffraction. The results indicate that Al(III) in the concentration range of 10-100 microM induced the following structural and functional effects: (i) change in the normal discoid shape of human erythrocytes to echinocytes due to the accumulation of Al(III) ions in the outer moiety of the red cell membrane; (ii) perturbation of dimyristoylphosphatidylcholine, and to a lesser extent of dimyristoylphosphatidylethanolamine bilayers, and (iii) decrease in the short-circuit current and in the potential difference of the isolated toad skin, effects that are in accordance with a time-dependent modulation of ion transport in response to changes in the molecular structure of the lipid bilayer.