CLONING OF A PUTATIVE GLUTAMATE RECEPTOR - A LOW AFFINITY KAINATE-BINDING SUBUNIT

Kainate, a glutamate receptor agonist, is a potent neuroexcitatory agent that produces epileptiform activity and selective neuronal degeneration. Binding studies using neuronal membrane homogenates or brain sections have identified sites having either high or low affinity for [H-3]kainate. Here we report the cloning of a gene, GluR7, with approximately 75% sequence identity with the previously cloned GluR5 and GluR6 subunit genes. Transcripts of the GluR7 gene are evident in brain areas that bind [H-3]kainate and are susceptible to kainate-induced neurotoxicity. We have performed ligand binding studies with membranes of transfected HeLa cells expressing GluR6 or GluR7 subunits. Our data show that the GluR6 and GluR7 subunits have a rank order of agonist affinity (domoate > kainate >> L-glutamate, quisqualate >> AMPA, NMDA) and a dissociation constant for kainate (95 and 77 nM, respectively) characteristic of the low affinity kainate-binding sites described in the brain.