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+).
Hu
W-P
WP
Department of Physiology, Xianning College, Xianning 437100, PR China. wangping_hu@yahoo.com
Li
X-M
XM
Chen
J-G
JG
Li
Z-W
ZW
D000535:Aluminum / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D018678:Cholinergic Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D008564:Membrane Potentials / Q000187:drug effects / Q000528:radiation effects; D009474:Neurons / Q000187:drug effects*; D009498:Neurotoxins / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000502:physiology*; D012668:Trigeminal Ganglion / Q000166:cytology
D018678:Cholinergic Agents; D009498:Neurotoxins; D011978:Receptors, Nicotinic; D009538:Nicotine; D000535:Aluminum