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Chronic ethanol consumption enhances internalization of α1 subunit‐containing GABA A receptors in cerebral cortex
Author(s) -
Kumar S.,
Kralic J. E.,
O'Buckley T. K.,
Grobin A. C.,
Morrow A. L.
Publication year - 2003
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 - 10.1046/j.1471-4159.2003.01894.x
Subject(s) - flunitrazepam , internalization , protein subunit , receptor , clathrin , immunoprecipitation , chemistry , gabaa receptor , cytosol , ethanol , biochemistry , biology , medicine , endocrinology , endocytosis , enzyme , gene
The molecular mechanisms that underlie ethanol dependence involve alterations in the functional properties and subunit expression of GABA A receptors. Chronic ethanol exposure decreases GABA A receptor α1 subunits and increases α4 subunit levels in cerebral cortical membranes. This study explored the effect of chronic ethanol exposure on internalization of GABA A /benzodiazepine receptors. Chronic ethanol exposure increased α1 subunit levels by 46 ± 12% and [ 3 H]flunitrazepam binding by 35 ± 9% in the clathrin‐coated vesicle (CCV) fraction. There was a corresponding 34 ± 8% decrease in α1 peptide expression and 37 ± 6% decrease in [ 3 H]flunitrazepam binding in the synaptic fraction. Chronic ethanol consumption also increased the α1 subunit immunoprecipitate in the cytosolic fraction (77 ± 22%), measured by western blot analysis. Moreover, co‐immunoprecipitation of both clathrin and adaptin‐α with α1 subunits was increased in the cytosolic fraction, suggesting that α1 subunit endocytosis is enhanced by chronic ethanol consumption. In contrast, α4 subunit peptide levels were not altered in the CCV fraction despite a 39 ± 13% increase in peptide levels in the synaptic fraction of cortex. Moreover, acute ethanol exposure did not alter α1 subunit peptide expression or [ 3 H]flunitrazepam binding in the synaptic or CCV fractions. These results suggest that chronic ethanol consumption selectively increases internalization of α1 subunit‐containing GABA A receptors in cerebral cortex.