TY - JOUR
T1 - AMPA receptor activates a G-protein that suppresses a cGMP-gated current
AU - Kawai, Fusao
AU - Sterling, Peter
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 1999/4/15
Y1 - 1999/4/15
N2 - 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.
AB - 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.
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U2 - 10.1523/jneurosci.19-08-02954.1999
DO - 10.1523/jneurosci.19-08-02954.1999
M3 - Article
C2 - 10191313
AN - SCOPUS:0033560870
VL - 19
SP - 2954
EP - 2959
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 8
ER -