Abstract
KAINIC acid is a potent neurotoxin for certain neurons1. Its neurotoxicity is thought to be mediated by an excitatory amino-acid-gated ion channel (ionotropic receptor) possessing nanomolar affinity for kainate2. 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 α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunits GluR-A to -D3–5. 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 > quisqualate > glutamate » AMPA) with a dissociation constant of about 5 nM for kainate2,6. 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 sites7–9. This correlation, as well as the particular in vivo pattern of neurodegeneration observed on kainate-induced neurotoxicity1,2, suggests that KA-1 participates in receptors mediating the kainate sensitivity of neurons in the central nervous system.
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Werner, P., Voigt, M., Keinänen, K. et al. Cloning of a putative high-affinity kainate receptor expressed predominantly in hippocampal CA3 cells. Nature 351, 742–744 (1991). https://doi.org/10.1038/351742a0
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DOI: https://doi.org/10.1038/351742a0
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