Potentiation of the nicotinic acetylcholine receptor by aluminum in mammalian neurons

Aluminum (Al3+), a known neurotoxic substance, has long been implicated in the pathogenesis of Alzheimer’s disease and other neurodegenerative diseases. Al3+ targets many ligand-gated and voltage-gated ion channels and modulates their functions. In the present study, the actions of Al3+ on the nicotinic acetylcholine receptor (nAChR) were investigated by whole-cell patch clamp technique in acutely isolated rat trigeminal ganglion neurons. We observed that Al3+ potentiated nicotine-evoked inward currents in a concentration-dependent manner (10–1000 μM). The effects of Al3+ on nicotine-evoked currents were voltage independent. Al3+ appeared to increase the affinity of nicotine to nAChR but not the efficacy. Al3+ reduced the agonist concentration producing a half-maximal response (EC50) for nicotine from 74.4±1.9 μM to 32.9±2.6 μM, but did not alter the threshold nor maximal response. On the contrary, another trivalent cation, Ga3+, had little effect on nicotine-evoked currents. The present results indicated that Al3+ enhanced the function of nAChR and this potentiation might underlie the neurological alteration induced by Al3+.