A role for extracellular Na+ in the channel gating of native and recombinant kainate receptors

Ana V. Paternain, Adir Cohen, Yael Stern-Bach, Juan Lerma*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Ionotropic glutamate receptors of the kainate and AMPA subtypes share a number of structural features, both topographical and in terms of stoichiometry. In addition, AMPA and kainate receptors share similar pharmacological and biophysical properties in that they are activated by common agonists and display rapid activation and desensitization characteristics. However, we show here that in contrast to AMPA receptor-mediated responses (native or recombinant GluR3 receptor), the response of native and recombinant (GluR6) kainate receptors to glutamate was drastically reduced in the absence of extracellular Na+ (i.e., when replaced by Cs+). Removal of Na+ increases the rate of desensitization, indicating that external Na+ modulates channel gating. Whereas the size of the substituting cation is important in mimicking the action of Na+ (Li+>K+>Cs+), modulation was voltage independent. These results indicate the existence of different gating mechanisms for AMPA and kainate receptors. By using chimeric AMPA-kainate receptors derived from GluR3 and GluR6, we have identified a key residue in the S2 segment of GluR6 (M770) that is largely responsible for the sensitivity of the receptor to external Na+. Thus, these results show the existence of a specific kainate receptor gating mechanism that requires external Na + to be operative.

Original languageAmerican English
Pages (from-to)8641-8648
Number of pages8
JournalJournal of Neuroscience
Volume23
Issue number25
DOIs
StatePublished - 24 Sep 2003

Keywords

  • AMPA
  • Allosteric modulation
  • Channel gating
  • Chimeras
  • GluR3
  • GluR6
  • Glutamate
  • KA2
  • Kainate
  • Receptors
  • Structure-function

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