Paradoxical effect of ethanol on potassium channel currents and cell survival in cerebellar granule neurons |
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Authors: | Thomas Lefebvre,Bruno J. Gonzalez&dagger &Dagger ,David Vaudry,Laurence Desrues,Antony Falluel-Morel,Nicolas Aubert§ ,Alain Fournier¶ ,Marie-Christine Tonon,Hubert Vaudry, Hé lè ne Castel |
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Affiliation: | Inserm U413, Laboratory of Neuroendocrine and Neuronal Cell Differentiation and Communication, European Institute for Peptide Research (IFRMP 23), University of Rouen, Mont-Saint-Aignan, France; NeoVascular Laboratory of Microvascular Endothelium and Neonate Brain Lesions, Rouen Institute for Biomedical Research, European Institute for Peptide Research (IFRMP 23), University of Rouen, Mont-Saint-Aignan, France; Department of Neonatal Paediatrics and Intensive Care, Rouen University Hospital, Rouen, France; International Center of Toxicology, Evreux, France; Institut National de la Recherche Scientifique-Institut Armand Frappier, University of Québec, Pointe-Claire, Canada |
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Abstract: | Transient exposure to ethanol (EtOH) results in a massive neurodegeneration in the developing brain leading to behavioral and cognitive deficits observed in fetal alcohol syndrome. There is now compelling evidence that K+ channels play an important role in the control of programmed cell death. The aim of the present work was to investigate the involvement of K+ channels in the EtOH-induced cerebellar granule cell death and/or survival. At low and high concentrations, EtOH evoked membrane depolarization and hyperpolarization, respectively. Bath perfusion of EtOH (10 mM) depressed the I A (transient K+ current) potassium current whereas EtOH (400 mM) provoked a marked potentiation of the specific I K (delayed rectifier K+ current) current. Pipette dialysis with GTPγS or GDPβS did not modify the effects of EtOH (400 mM) on both membrane potential and I K current. In contrast, the reversible depolarization and slowly recovering inhibition of I A induced by EtOH (10 mM) became irreversible in the presence of GTPγS. EtOH (400 mM) induced prodeath responses whereas EtOH (10 mM) and K+ channel blockers promoted cell survival. Altogether, these results indicate that in cerebellar granule cells, EtOH mediates a dual effect on K+ currents partly involved in the control of granule cell death. |
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Keywords: | cell survival delayed rectifier ethanol fast-inactivating granule neuron potassium currents |
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