title: The delayed rectifier channel current IK plays a key role in the control of programmed cell death by PACAP and ethanol in cerebellar granule neurons.
abstract: Alcohol exposure during development causes severe brain malformations, and thus, identification of molecules that can counteract the neurotoxicity of ethanol deserves high priority. Since activation of potassium (K+) currents has been shown to play a critical role in the control of programmed cell death, we have investigated the effects of ethanol and PACAP on K+ currents in cultured cerebellar granule cells using the patch-clamp technique in the whole cell configuration. In the presence of the fast-inactivating IA current blocker 4-AP, a focal application of ethanol (200 mM) in the vicinity of granule cells provoked a robust hyperpolarization and a marked increase of the delayed rectifier IK current. Addition of PACAP (0.1 microM) in the bath solution prevented ethanol-induced membrane hyperpolarization and suppressed the stimulatory effect of ethanol on IK current. These data suggest that ethanol alters neuronal survival, at least in part, through activation of IK, and that PACAP abolishes ethanol-induced cerebellar granule cell death via inhibition of IK..
authors.affiliation: INSERM U413, Laboratory of Cellular and Molecular Neuroendocrinology, European Institute for Peptide Research (IFRMP 23), University of Rouen, 76821 Mont-Saint-Aignan, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Castel
authors.forename: David
authors.initials: D
authors.lastname: Vaudry
authors.forename: Yan-Ai
authors.initials: YA
authors.lastname: Mei
authors.forename: Thomas
authors.initials: T
authors.lastname: Lefebvre
authors.forename: Magali
authors.initials: M
authors.lastname: Basille
authors.forename: Laurence
authors.initials: L
authors.lastname: Desrues
authors.forename: Alain
authors.initials: A
authors.lastname: Fournier
authors.forename: Hubert
authors.initials: H
authors.lastname: Vaudry
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Tonon
authors.forename: Bruno J
authors.initials: BJ
authors.lastname: Gonzalez
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D004594:Electrophysiology; D000431:Ethanol / Q000494:pharmacology*; D015640:Ion Channel Gating; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology*; D015221:Potassium Channels / Q000378:metabolism*
chemical_list: D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D015221:Potassium Channels; D000431:Ethanol