Potentiation of the nicotinic acetylcholine receptor by aluminum in mammalian neurons

• Published in: Neuroscience Vol. 149; no. 1; pp. 1 - 6
• Main Authors: Hu, W.-P, Li, X.-M, Chen, J.-G, Li, Z.-W
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 12.10.2007; Elsevier
• Subjects: aluminum; Aluminum - pharmacology; Animals; Animals, Newborn; Biological and medical sciences; Cells, Cultured; Cholinergic Agents - pharmacology; current; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Drug Interactions; Electric Stimulation - methods; Fundamental and applied biological sciences. Psychology; Membrane Potentials - drug effects; Membrane Potentials - radiation effects; Neurology; neuron; Neurons - drug effects; Neurotoxins - pharmacology; Nicotine - pharmacology; nicotinic acetylcholine receptor; Patch-Clamp Techniques - methods; potentiation; Rats; Rats, Sprague-Dawley; Receptors, Nicotinic - physiology; Trigeminal Ganglion - cytology; Vertebrates: nervous system and sense organs; Al 3; Hepes; neuron; trigeminal ganglion; aluminum; α-BTx; DMEM; current; GDP-β-S; I-V; dimethylphenylpiperazinium; potentiation; nAChR; I nic(ss); atropine; nicotinic acetylcholine receptor; Tub; agonist concentration producing a half-maximal response; I nic; DMPP; peak values of nicotine-activated current; gallium; Ga 3; N-(2-hydroxyethyl)piperazine- N′-(2-ethanesulfonic acid); tubocurarine; EGTA; guanosine 5′-O-(2-thiodiphosphate); TG; EC 50; I nic(p); current-voltage; α-bungarotoxin; ethylene glycol-bis(2-aminoethylether)- N, N, N′,N′-tetraacetic acid; Hex; steady state component of nicotine-activated current; hexamethonium; Atr; Dulbecco’s Modified Eagle medium; nicotine-activated current; Potentiation; Vertebrata; Cholinergic receptor; Mammalia; Neuron; Nicotinic receptor
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2007.07.018

Abstract 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+.