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The Journal of Neuroscience, April 15, 1999, 19(8):2954-2959
AMPA Receptor Activates a G-Protein that Suppresses a
cGMP-Gated Current
Fusao
Kawai1, 2 and
Peter
Sterling1
1 Department of Neuroscience, University of
Pennsylvania, Philadelphia, Pennsylvania 19104-6058, and
2 Department of Information Physiology, National Institute
for Physiological Sciences, Okazaki 444, Japan
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- -S, whereas the suppression is irreversible when the
pipette contains GTP- -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.
Key words:
AMPA; glutamate; ionotropic; metabotropic; G-protein; retina; rat
Copyright © 1999 Society for Neuroscience 0270-6474/99/1982954-06$05.00/0
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