AMPA receptor activates a G-protein that suppresses a cGMP-gated current

Fusao Kawai, Peter Sterling

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)

Abstract

The AMPA receptor, ubiquitous in brain, is termed 'ionotropic' because it gates an ion channel directly. We found that an AMPA receptor can also modulate a G-protein to gate an ion channel indirectly. Glutamate applied to a retinal ganglion cell briefly suppresses the inward current through a cGMP- gated channel. AMPA and kainate also suppress the current, an effect that is blocked both by their general antagonist CNQX and also by the relatively specific AMPA receptor antagonist GYKI-52466. Neither NMDA nor agonists of metabotropic glutamate receptors are effective. The AMPA-induced suppression of the cGMP-gated current is blocked when the patch pipette includes GDP-β- S, whereas the suppression is irreversible when the pipette contains GTP-γ- S. This suggests a G-protein mediator, and, consistent with this, pertussis toxin blocks the current suppression. Nitric oxide (NO) donors induce the current suppressed by AMPA, and phosphodiesterase inhibitors prevent the suppression. Apparently, the AMPA receptor can exhibit a 'metabotropic' activity that allows it to antagonize excitation evoked by NO.

Original languageEnglish
Pages (from-to)2954-2959
Number of pages6
JournalJournal of Neuroscience
Volume19
Issue number8
DOIs
Publication statusPublished - 15-04-1999
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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