Differential activation of individual subunits in heteromeric kainate receptors

Neuron. 2002 May 16;34(4):589-98. doi: 10.1016/s0896-6273(02)00676-1.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
  • Alanine / analogs & derivatives*
  • Alanine / pharmacology
  • Binding Sites / drug effects
  • Binding Sites / genetics
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Cells, Cultured
  • Central Nervous System / metabolism*
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Glutamic Acid / metabolism
  • Glutamic Acid / pharmacology
  • Humans
  • Macromolecular Substances
  • Models, Neurological
  • Mutagenesis, Site-Directed / genetics
  • Mutation / genetics
  • Neurons / metabolism*
  • Receptors, Kainic Acid / drug effects
  • Receptors, Kainic Acid / genetics
  • Receptors, Kainic Acid / metabolism*
  • Synapses / metabolism*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*


  • Bridged Bicyclo Compounds, Heterocyclic
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Gluk1 kainate receptor
  • Gluk2 kainate receptor
  • Macromolecular Substances
  • Receptors, Kainic Acid
  • dysiherbaine
  • Glutamic Acid
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • Alanine