Heteromeric kainate receptors formed by the coassembly of GluR5, GluR6, and GluR7

In the CNS kainate subtype glutamate receptors (GluRs) are likely to be het eromeric assemblies containing multiple gene products. However, although re combinant kainate receptors from the GluR5-GluR7 gene family have been stud ied extensively in their homomeric forms, there have been no tests to deter mine whether these subunits can coassemble with each other. We used the Glu R5 selective agonists (RS)-2-amino-3(3-hydroxy-5-tertbutylisoxazol-4-yl) pr opanoic acid (ATPA) and (S)-5-iodowillardiine (I-will) to test for the coas sembly of GluR5 with GluR6 and GluR7 by measuring changes in rectification that occur for heteromeric receptors containing both edited and unedited Q/ R site subunits. Birectifying ATPA and I-will responses resulting from poly amine block for homomeric GluR5(Q) became outwardly rectifying when GluR6(R ) was coexpressed with GluR5(Q), although GluR6 was not activated by ATPA o r I-will, indicating the formation of heteromeric receptors. Similar approa ches showed the coassembly of GluR7 with GluR6 and GluR5. Heteromeric kaina te receptors containing both GluR5 and GluR6 subunits exhibited novel funct ional properties, including reduced desensitization and faster recovery fro m desensitization than those recorded for homomeric GluR5. Coexpression of GluR6 with GluR5 also enhanced the magnitude of responses to GluR5 selectiv e agonists. In contrast, the coassembly of GluR7 with GluR6 markedly decrea sed the amplitude of agonist responses. Our results indicate that, similar to AMPA receptors, the kainate receptor subunits GluR5-GluR7 exhibit promis cuous coassembly. The formation of heteromeric kainate receptors may help t o explain why the functional properties of native kainate receptors differ from those that have been reported for recombinant kainate receptors.