Ethanol withdrawal upregulates kainate receptors in cultured rat hippocampal neurons.
We have previously demonstrated that kainate receptors (KA-Rs) are acutely inhibited by ethanol (EtOH). Here we show that KA-Rs are also affected by long-term EtOH exposure. Whole-cell recordings of pharmacologically isolated KA-R-mediated currents in cultured hippocampal neurons revealed that exposure to 80 mM EtOH for 3 days followed by a 24 h withdrawal period increased KA-R current densities. Quantitative confocal microscopy showed that expression of GluR6/7 subunits increases after ethanol withdrawal in these neurons. Since KA-Rs control hippocampal excitability and seizure generation, we postulate that upregulation of these receptors may have a role in the pathophysiology of alcohol withdrawal syndrome.
Carta
Mario
M
Department of Neurosciences, University of New Mexico Health Sciences Center, Albuquerque, NM 87131-5223, USA.
Olivera
Dorian S
DS
Dettmer
Todd S
TS
Valenzuela
C Fernando
CF
D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D018092:Kainic Acid Receptors / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D001569:Benzodiazepines; D002492:Central Nervous System Depressants; D000431:Ethanol; D018092:Kainic Acid Receptors; C118651:GYKI 53784