The alpha 7 nicotinic acetylcholine receptor subtype mediates nicotine protection against NMDA excitotoxicity in primary hippocampal cultures through a Ca2+ dependent mechanism

F A Dajas-Bailador, P A Lima, S Wonnacott

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169 Citations (Scopus)

Abstract

Neuronal nicotinic acetylcholine receptors (nAChR) have been suggested to play a role in a variety of modulatory and regulatory processes, including neuroprotection. Here we have characterized the neuroprotective effects of nicotine against an excitotoxic insult in primary hippocampal cultures. Exposure of hippocampal neurons to 200 muM NMDA for 1 h decreased eel viability by 25+/-5%, an effect blocked by NMDA receptor antagonists. Nicotine (10 muM) counteracted the NMDA-induced cell death when co-incubated with NMDA or when present subsequent to the NMDA treatment. Nicotine protection was prevented by 1 muM MLA, confirming that it was mediated by nAChR, and by 1 muM alpha -bungarotoxin, demonstrating that the alpha7 nAChR subtype was responsible. Both the NMDA evoked neurotoxicity and nicotine neuroprotection were Ca2+-dependent. In Fura-2-loaded hippocampal neurons, nicotine (10 muM) and NMDA (200 muM) acutely increased intracellular resting Ca2+ from 70 nM to 200 and 500 nM, respectively. Responses to NMDA were unaffected by the presence of nicotine. Ca-45(2+) uptake after a 1 h exposure to nicotine or NMDA also demonstrated quantitative differences between the two drugs. This study demonstrates that the alpha7 subtype of nAChR can support neuronal survival after an excitotoxic stimulus, through a Ca2+ dependent mechanism that operates downstream of NMDA receptor activation.
Original languageEnglish
Pages (from-to)2799-2807
Number of pages9
JournalNeuropharmacology
Volume39
Issue number13
DOIs
Publication statusPublished - Dec 2000

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