Differential activation of individual subunits in heteromeric kainate receptors.
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.
Swanson
Geoffrey T
GT
Department of Pharmacology and Toxicology, University of Texas Medical Branch, 301 University Boulevard, Galveston 77555, USA. g.swanson@utmb.edu
Green
Tim
T
Sakai
Ryuichi
R
Contractor
Anis
A
Che
Wesley
W
Kamiya
Hisao
H
Heinemann
Stephen F
SF
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
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