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.
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..
Castel
Hélène
H
INSERM U413, Laboratory of Cellular and Molecular Neuroendocrinology, European Institute for Peptide Research (IFRMP 23), University of Rouen, 76821 Mont-Saint-Aignan, France.
Vaudry
David
D
Mei
Yan-Ai
YA
Lefebvre
Thomas
T
Basille
Magali
M
Desrues
Laurence
L
Fournier
Alain
A
Vaudry
Hubert
H
Tonon
Marie-Christine
MC
Gonzalez
Bruno J
BJ
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*
D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D015221:Potassium Channels; D000431:Ethanol