Cloning of a putative high-affinity kainate receptor expressed predominantly in hippocampal CA3 cells.
Kainic acid is a potent neurotoxin for certain neurons. Its neurotoxicity is thought to be mediated by an excitatory amino-acid-gated ion channel (ionotropic receptor) possessing nanomolar affinity for kainate. 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. The pharmacological profile of expressed recombinant KA-1 determined in binding experiments with [3H]kainate is different from that of the cloned AMPA receptors and similar to the mammalian high-affinity kainate receptor (kainate greater than quisqualate greater than glutamate much greater than AMPA) with a dissociation constant of about 5 nM for kainate. 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. This correlation, as well as the particular in vivo pattern of neurodegeneration observed on kainate-induced neurotoxicity, suggests that KA-1 participates in receptors mediating the kainate sensitivity of neurons in the central nervous system.
Werner
P
P
Laboratory of Molecular Neuroendocrinology, Centre for Molecular Biology, University of Heidelberg, Germany.
Voigt
M
M
Keinänen
K
K
Wisden
W
W
Seeburg
P H
PH
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D007608:Kainic Acid / Q000378:metabolism; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018092:Kainic Acid Receptors; D017981:Receptors, Neurotransmitter / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D014018:Tissue Distribution; D014162:Transfection
D007608:Kainic Acid; D012333:RNA, Messenger; D018092:Kainic Acid Receptors; D017981:Receptors, Neurotransmitter; D011994:Recombinant Proteins