Acute effects of ethanol on kainate receptors with different subunit compositions

Previous studies showed that recombinant homomeric GluR6 receptors are acut ely inhibited by ethanol. This study examined the acute actions of ethanol on recombinant homomeric and heteromeric kainate (KA) receptors with differ ent subunit configurations. Application of 25 to 100 mM ethanol produced in hibition of a similar magnitude of both GluR5-Q and GluR6-R KA receptor-dep endent currents in Xenopus oocytes. Ethanol decreased the KA E-max without affecting the EC,, and its effect was independent of the membrane holding p otential for both of these receptors subtypes. Ethanol also inhibited homom eric and heteromeric receptors transiently expressed in human embryonic kid ney (HEK) 293 cells. In these cells, the expression of heteromeric GluR6-R subunit-containing receptors was confirmed by testing their sensitivity to 1 mM alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid. Ethanol inh ibited to a similar extent KA-gated currents mediated by receptors composed of either GluR6 or GluR6 + KA1 subunits, and to a slightly lesser extent r eceptors composed of GluR6 + KA2 subunits. Acute ethanol's effects were tes ted on GluR5 KA receptors that are expressed as homomers (GluR5-Q) or heter omers (GluR5-R + KA1 and GluR5-R + KA2). Homomeric and heteromeric GluR5 KA receptors were all inhibited to a similar extent by ethanol; however, ther e was slightly more inhibition of GluR5-R + KA2 receptors. Thus, recombinan t KA receptors with different subunit compositions are all acutely inhibite d to a similar extent by ethanol. In light of recent reports that KA recept ors regulate neurotransmitter release and mediate synaptic currents, we pos tulate that these receptors may play a role in acute ethanol intoxication.