Paradoxical effect of ethanol on potassium channel currents and cell survival in cerebellar granule neurons.
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 GTPgammaS or GDPbetaS 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 GTPgammaS. 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.
Lefebvre
Thomas
T
Laboratory of Neuroendocrine and Neuronal Cell Differentiation and Communication, European Institute for Peptide Research, University of Rouen, Mont-Saint-Aignan, France.
Gonzalez
Bruno J
BJ
Vaudry
David
D
Desrues
Laurence
L
Falluel-Morel
Antony
A
Aubert
Nicolas
N
Fournier
Alain
A
Tonon
Marie-Christine
MC
Vaudry
Hubert
H
Castel
Hélène
H
D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D000431:Ethanol / Q000008:administration & dosage*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D000431:Ethanol