Potentiation of the nicotinic acetylcholine receptor by aluminum in mammalian neurons.

Aluminum (Al(3+)), a known neurotoxic substance, has long been implicated in the pathogenesis of Alzheimer's disease and other neurodegenerative diseases. Al(3+) targets many ligand-gated and voltage-gated ion channels and modulates their functions. In the present study, the actions of Al(3+) on the nicotinic acetylcholine receptor (nAChR) were investigated by whole-cell patch clamp technique in acutely isolated rat trigeminal ganglion neurons. We observed that Al(3+) potentiated nicotine-evoked inward currents in a concentration-dependent manner (10-1000 microM). The effects of Al(3+) on nicotine-evoked currents were voltage independent. Al(3+) appeared to increase the affinity of nicotine to nAChR but not the efficacy. Al(3+) reduced the agonist concentration producing a half-maximal response (EC(50)) for nicotine from 74.4+/-1.9 microM to 32.9+/-2.6 microM, but did not alter the threshold nor maximal response. On the contrary, another trivalent cation, Ga(3+), had little effect on nicotine-evoked currents. The present results indicated that Al(3+) enhanced the function of nAChR and this potentiation might underlie the neurological alteration induced by Al(3+).