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

The AMPA receptor, ubiquitous in brain, is termed "ionotropic" because it g ates an ion channel directly. We found that an AMPA receptor can also modul ate a G-protein to gate an ion channel indirectly. Glutamate applied to a r etinal ganglion cell briefly suppresses the inward current through a cGMP-g ated channel. AMPA and kainate also suppress the current, an effect that is blocked both by their general antagonist CNQX and also by the relatively s pecific AMPA receptor antagonist GYKI-52466. Neither NMDA nor agonists of m etabotropic glutamate receptors are effective. The AMPA-induced suppression of the cGMP-gated current is blocked when the patch pipette includes GDP-b eta-S, whereas the suppression is irreversible when the pipette contains GT P-gamma-S. This suggests a G-protein mediator, and, consistent with this, p ertussis toxin blocks the current suppression. Nitric oxide (NO) donors ind uce the current suppressed by AMPA, and phosphodiesterase inhibitors preven t the suppression. Apparently, the AMPA receptor can exhibit a "metabotropi c" activity that allows it to antagonize excitation evoked by NO.