title: Differential activation of individual subunits in heteromeric kainate receptors.
abstract: Neuronal kainate receptors are assembled from subunits with dissimilar specificities for agonists and antagonists. The composite biophysical behavior of heteromeric kainate receptors is determined by intersubunit interactions whose nature is unclear. Here we use dysiherbaine, a selective kainate receptor agonist, to show that GluR5 subunits assembled in heteromeric GluR5/KA-2 kainate receptor complexes can gate current without concomitant activation of their partner KA-2 subunits. A long-lasting interaction between dysiherbaine and GluR5 subunits elicits a tonic current from GluR5/KA-2 receptors; subsequent cooperative gating of KA-2 subunits can be elicited by both agonists, such as glutamate, and some classically defined antagonists, such as CNQX. This study demonstrates that each type of subunit within a heteromeric kainate receptor contributes a distinct conductance upon activation by agonist binding, and therefore provides insight into the biophysical function of ionotropic glutamate receptors.
authors.affiliation: Department of Pharmacology and Toxicology, University of Texas Medical Branch, 301 University Boulevard, Galveston 77555, USA. g.swanson@utmb.edu
authors.forename: Geoffrey T
authors.initials: GT
authors.lastname: Swanson
authors.forename: Tim
authors.initials: T
authors.lastname: Green
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Sakai
authors.forename: Anis
authors.initials: A
authors.lastname: Contractor
authors.forename: Wesley
authors.initials: W
authors.lastname: Che
authors.forename: Hisao
authors.initials: H
authors.lastname: Kamiya
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Heinemann
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects / Q000235:genetics; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D046911:Macromolecular Substances; D008959:Models, Neurological; D016297:Mutagenesis, Site-Directed / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D000097806:GluK2 Kainate Receptor
chemical_list: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000409:Alanine; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D046911:Macromolecular Substances; D018092:Kainic Acid Receptors; D000097806:GluK2 Kainate Receptor; C121741:dysiherbaine