CLONING OF A PUTATIVE HIGH-AFFINITY KAINATE RECEPTOR EXPRESSED PREDOMINANTLY IN HIPPOCAMPAL CA3 CELLS

KAINIC acid is a potent neurotoxin for certain neurons 1. Its neurotoxicity is thought to be mediated by an excitatory amino-acid-gated ion channel (ionotropic receptor) possessing nanomolar affinity for kainate 2. Here we describe a new member of the rat excitatory amino-acid receptor gene family, KA-1, that has a 30% sequence similarity with the previously characterized alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunits GluR-A to -D 3-5. The pharmacological profile of expressed recombinant KA-1 determined in binding experiments with [H-3]kainate is different from that of the cloned AMPA receptors and similar to the mammalian high-affinity kainate receptor (kainate > quisqualate > glutamate >> AMPA) with a dissociation constant of about 5 nM for kainate 2,6. The selectively high expression of KA-1 messenger RNA in the CA3 region of the hippocampus closely corresponds to autoradiographically located high-affinity kainate binding sites 7-9. This correlation, as well as the particular in vivo pattern of neurodegeneration observed on kainate-induced neurotoxicity 1,2, suggests that KA participates in receptors mediating the kainate sensitivity of neurons in the central nervous system.