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

Abstract

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.

• Authors: R A Jacoby, S M Wu
• Journal: Visual neuroscience (Vis Neurosci) 2001 Sep-Oct Vol. 18 Issue 5 Pg. 703-10 ISSN: 0952-5238 [Print] England
• PMID: 11925006 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• 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

Topics

• 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, metabolism)
• Receptors, Kainic Acid (antagonists & inhibitors, metabolism)
• Receptors, N-Methyl-D-Aspartate (metabolism)
• Retinal Ganglion Cells (drug effects, metabolism)