Atypical functional properties of GluK3-containing kainate receptors

J Neurosci. 2009 Dec 9;29(49):15499-510. doi: 10.1523/JNEUROSCI.2724-09.2009.

Abstract

The properties of synaptic receptors determine their mode of action at presynaptic and postsynaptic loci. Here, we investigated the atypical biophysical properties of GluK3-containing kainate receptors, which contribute to presynaptic facilitation at hippocampal mossy fiber synapses. We show, using fast glutamate applications on outside-out patches and kinetic modeling, that the low sensitivity of GluK3 receptors for glutamate is attributable to fast desensitization of partially bound receptors. Consequently, these receptors can only be activated by fast transients of high glutamate concentration. In addition, GluK3 receptors are very sensitive to voltage-dependent block by intracellular spermine that precludes activation of substantial currents at potentials positive to -50 mV. Two specific residues within the channel pore define this high-affinity site. Finally, GluK3 are calcium permeable in the same way as unedited GluK2 receptors. These receptors present unique properties among AMPA/kainate receptors that could reflect a specialized presynaptic function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Calcium / metabolism
  • Cell Line
  • GluK2 Kainate Receptor
  • GluK3 Kainate Receptor
  • Glutamic Acid / chemistry
  • Glutamic Acid / metabolism
  • Hippocampus / chemistry
  • Hippocampus / physiology
  • Humans
  • Intracellular Space / chemistry
  • Intracellular Space / metabolism
  • Kinetics
  • Membrane Potentials / physiology
  • Models, Neurological
  • Molecular Sequence Data
  • Mutation
  • Neurons / chemistry
  • Neurons / physiology
  • Patch-Clamp Techniques
  • Receptors, Kainic Acid / chemistry*
  • Receptors, Kainic Acid / genetics
  • Receptors, Kainic Acid / metabolism*
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Spermine / chemistry
  • Spermine / metabolism

Substances

  • Receptors, Kainic Acid
  • Spermine
  • Glutamic Acid
  • Calcium