AMPA-preferring receptors mediate excitatory non-NMDA responses of primate retinal ganglion cells

Vis Neurosci. 2001 Sep-Oct;18(5):703-10. doi: 10.1017/s0952523801185044.


Glutamate and kainate-induced currents of primate ganglion cells were studied using the whole-cell patch-clamp technique in a retinal slice preparation. Antagonists and allosteric modulators of desensitization selective for either alpha-amino-3-hydroxy-5-methyl-4-isoazoleprionic acid (AMPA)- or kainate-preferring receptors were used to determine the contributions of each type of receptor to excitatory responses. With synaptic transmission and NMDA receptors blocked, the AMPA-preferring receptor antagonist GYKI 52466 (30 microM-100 microM) reversibly blocked most of the glutamate-induced current in ganglion cells. GYKI 52466 also blocked the response in ganglion cells to focally applied kainate, suggesting that the current response to kainate arises from activation of AMPA-preferring receptors, and not kainate-preferring receptors. Both cyclothiazide (10 microM-100 microM) and the novel drug 4-[2-(phenylsulfonylamino)ethylthio]-2,6-difluoro-phenoxyacetamide (PEPA, 20 microM-100 microM), which selectively enhance responses mediated by AMPA-preferring receptors, enhanced glutamate-induced responses of ganglion cells. Since these drugs preferentially inhibit desensitization of the flip and flop splice variants, respectively, of AMPA-preferring receptors, it is likely that both splice variants are present on these ganglion cells. Concanavalin A, which selectively suppresses the desensitization of kainate-preferring receptors, had no effect on the glutamate-induced responses of ganglion cells. We conclude that the non-NMDA component of the excitatory, glutamatergic input to primate ganglion cells is mediated largely by AMPA-preferring receptors, with little, if any, kainate-preferring receptor-mediated response.

Publication types

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

MeSH terms

  • Animals
  • Anti-Anxiety Agents / pharmacology
  • Benzodiazepines*
  • Benzothiadiazines / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Glutamic Acid / pharmacology
  • Kainic Acid / pharmacology
  • Macaca mulatta
  • Papio
  • Patch-Clamp Techniques
  • Phenoxyacetates / pharmacology
  • Receptors, AMPA / antagonists & inhibitors
  • Receptors, AMPA / metabolism*
  • Receptors, Kainic Acid / antagonists & inhibitors
  • Receptors, Kainic Acid / metabolism
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Retinal Ganglion Cells / drug effects
  • Retinal Ganglion Cells / metabolism*


  • 4-(2-(phenylsulfonylamino)ethylthio)-2,6-difluorophenoxyacetamide
  • Anti-Anxiety Agents
  • Benzothiadiazines
  • Excitatory Amino Acid Antagonists
  • Phenoxyacetates
  • Receptors, AMPA
  • Receptors, Kainic Acid
  • Receptors, N-Methyl-D-Aspartate
  • GYKI 52466
  • Benzodiazepines
  • Glutamic Acid
  • cyclothiazide
  • Kainic Acid