Photochemically knocking out glutamate receptors in vivo.


AMPA (alpha-amino-3-hydroxy-5-methyl-4-isooxazole) receptors, a major subtype of ionotropic glutamate receptors (iGluRs), mediate the majority of the fast communication between neurons, and the activity-dependent trafficking of AMPA receptors at synapses plays a role in mammalian learning and memory. Here we describe the design, synthesis, and evaluation of a photoreactive AMPA receptor antagonist that provides a means of "knocking out" AMPA receptors present on the surface of cells. The antagonist, 6-azido-7-nitro-1,4-dihydroquinoxaline-2,3-dione (ANQX), was designed by introducing a photoreactive azido group onto a quinoxalinedione inhibitor scaffold. Computational docking of ANQX to the AMPA receptor ligand-binding core predicted efficient binding to AMPA receptors. Glutamate-evoked currents were reversibly blocked at micromolar ANQX concentrations prior to photolysis and irreversibly blocked following photolysis. ANQX provides a means of directly evaluating the trafficking of native AMPA receptors with unparalleled spatiotemporal resolution.


Citations per Year

190 Citations

Semantic Scholar estimates that this publication has 190 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Chambers2004PhotochemicallyKO, title={Photochemically knocking out glutamate receptors in vivo.}, author={James J. Chambers and Hiroaki Gouda and David M. Young and Irwin D. Kuntz and Pamela M England}, journal={Journal of the American Chemical Society}, year={2004}, volume={126 43}, pages={13886-7} }