Despite many studies on the functional expression of neuronal nicotinic acetylcholine receptors (nAChRs), an exhaustive description of the long-term effects of nicotine (Nic) stimulation in cerebellar granules is still far to be completed. For this reason, we addressed the experiments stimulating cultured cerebellar granule neurons (CGN) with Nic, focusing on the effects on cell motility and survival. Using electrophysiological and Ca2+-fluorescence techniques, we found a subset of rat CGN that responded to Nic by inward whole cell currents and by short-delay Ca2+ transients. These responses were mediated through both homomeric and heteromeric nAChRs, as assessed by their sensitivity to alpha-bungarotoxin (alpha-BTX), dihydro-beta-erythroidine (DHbetaE), methyllicaconitine (MLA) and 5-hydroxyindole (5OH-indole). Once established the expression of alpha-BTX-sensitive and insensitive nAChRs and their ability to trigger Ca2+ responses in CGN, we aimed at investigating their possible role on cell survival and motility. We demonstrate that Nic stimulation significantly increases the survival of CGN exposed to the apoptosis-promoting low K+ medium. This anti-apoptotic effect is likely mediated through alpha7* nAChRs since we found that it was mimicked by choline, was insensitive to DHbetaE and was fully inhibited by alpha-BTX. Furthermore, we report that Nic negatively modulates CGN motility, reducing the basal cell movement through a pored membrane by the activation of alpha-BTX-insensitive nAChRs. We conclude that CGN express various types of nAChRs, which are differently involved in regulating Nic-mediated modulation of cell survival and migration, and we suggest potential regulatory roles for cholinergic receptors during cerebellar development. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved.
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|Titolo:||Nicotinic cholinergic stimulation promotes survival and reduces motility of cultured rat cerebellar granule cells|
|Data di pubblicazione:||2004|
|Appartiene alla tipologia:||01a Articolo in rivista|