The importance of two specific domains in ligand binding to the AMPA/kainate glutamate receptors GluR2 and GluR6

Chimeric receptor subunits of the AMPA receptor subunit GluR2 and the kainate receptor subunit GluR6 were constructed and stably expressed in baby hamster kidney cells. By using ca ²⁺ imaging and radioligand binding, we demonstrated that substitution of a specific domain showing homology to a bacterial leucine-isoleucine-valine binding protein (LIVBP) had no effect on the affinities of the tested agonists, but decreased the affinities of the antagonists CNQX, DNQX, and NBQX. On the other hand, when the first of two domains showing homology to a bacterial glutamine binding protein (QBP) in GluR2 was substituted with the corresponding region from GluR6, the affinity of AMPA decreased sevenfold and the affinity of kainate increased fourfold, indicating the importance of this domain in binding of these agonists. In contrast to this, the affinities of quisqualate and domoate, two other agonists, were unchanged, indicating that a region located C-terminal to the QBP domain is also involved in agonist binding.