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Paradoxical effect of ethanol on potassium channel currents and cell survival in cerebellar granule neurons
Author(s) -
Lefebvre Thomas,
Gonzalez Bruno J.,
Vaudry David,
Desrues Laurence,
FalluelMorel Antony,
Aubert Nicolas,
Fournier Alain,
To MarieChristine,
Vaudry Hubert,
Castel Hélène
Publication year - 2009
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.06197.x
Subject(s) - depolarization , chemistry , granule cell , potassium channel , neuroscience , biophysics , medicine , endocrinology , central nervous system , biology , dentate gyrus
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.