Effects of Al(III) speciation on cell membranes and molecular models

Aluminum, a very abundant metal, might play an important role in several pathologies which could be related to its interactions with cell membranes. 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 scarce. One reason for this lack of molecular information is the ill-defined chemical speciation of the metal compounds utilized in toxicological experimental protocols. Another is the complex molecular structure of cell membranes. For this reason, molecular models consisting in phospholipid bilayers are commonly used. In this review the interaction of four Al(III) compounds with phospholipid bilayers built-up of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE) and their effects on ion channels present in isolated toad skins are discussed. The aluminum compounds are Al(acac)₃, AlCl₃, AlF₃ and the Al-citrate complex K₅Al(C₆H₄O₇)₂]. It is concluded that they interact with and produce different structural and functional effects on the model and biological membranes. X-ray diffraction revealed that AlCl₃ (1 mM) induced the most damaging effects to both DMPC and DMPE bilayers whereas the Al-citrate complex caused only slight perturbation, the effects of Al(acac)₃ and AlF₃ being intermediate. The inhibitory effects on the isolated skin, in descending order, were (100 μM): AlCl₃, possibly by indirect and direct inactivation of Na⁺ channels and/or perturbation of an ATPase; AlF₃, by direct inactivation of the Na⁺ channel and mild ATPase inhibition; Al-citrate, by decrease of Na⁺ permeability, and lastly, Al(acac)₃, which decreased Na⁺ transport only at far higher concentration (250 μM).