Cloning of a cDNA for a glutamate receptor subunit activated by kainate but not AMPA.
Fast excitatory transmission in the vertebrate central nervous system is mediated mainly by L-glutamate. On the basis of pharmacological, physiological and agonist binding properties, the ionotropic glutamate receptors are classified into NMDA (N-methyl-D-aspartate), AMPA (alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate) and kainate subtypes. Sequence homology between complementary DNA clones encoding non-NMDA glutamate receptor subunits reveals at least two subunit classes: the GluR1 to GluR4 class and the GluR5 class. Here we report the cloning and expression of a functional rat glutamate receptor subunit cDNA, GluR6, which has a very different pharmacology from that of the GluR1-GluR4 class. Receptors generated from the GluR1-GluR4 class have a higher apparent affinity for AMPA than for kainate. When expressed in Xenopus oocytes the homomeric GluR6 receptor is activated by kainate, quisqualate and L-glutamate but not by AMPA, and the apparent affinity for kainate is higher than for receptors from the GluR1-GluR4 class. Desensitization of the receptor was observed with continuous application of agonist. The homomeric GluR6 glutamate receptor exhibits an outwardly rectifying current-voltage relationship. In situ hybridizations reveal a pattern of GluR6 gene expression reminiscent of the binding pattern obtained with [3H]kainate.
Egebjerg
J
J
Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037.
Bettler
B
B
Hermans-Borgmeyer
I
I
Heinemann
S
S
D000595:Amino Acid Sequence; D000818:Animals; D001923:Brain Chemistry; D002531:Cerebellum / Q000737:chemistry; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics*; D007051:Ibotenic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D007608:Kainic Acid / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D009865:Oocytes / Q000378:metabolism; D051381:Rats; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D014018:Tissue Distribution; D014162:Transfection; D014981:Xenopus; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D007051:Ibotenic Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D004247:DNA; D007608:Kainic Acid