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Issue 1, 2017
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Optical control of AMPA receptors using a photoswitchable quinoxaline-2,3-dione antagonist

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Abstract

AMPA receptors respond to the neurotransmitter glutamate and play a critical role in excitatory neurotransmission. They have been implicated in several psychiatric disorders and have rich pharmacology. Antagonists of AMPA receptors have been explored as drugs and one has even reached the clinic. We now introduce a freely diffusible photoswitchable antagonist that is selective for AMPA receptors and endows them with light-sensitivity. Our photoswitch, ShuBQX-3, is active in its dark-adapted trans-isoform but is significantly less active as its cis-isoform. ShuBQX-3 exhibits a remarkable red-shifting of its photoswitching properties through interactions with the AMPA receptor ligand binding site. Since it can be used to control action potential firing with light, it could emerge as a powerful tool for studying synaptic transmission with high spatial and temporal precision.

Graphical abstract: Optical control of AMPA receptors using a photoswitchable quinoxaline-2,3-dione antagonist

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Supplementary files

Article information


Submitted
12 Apr 2016
Accepted
01 Aug 2016
First published
24 Aug 2016

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2017,8, 611-615
Article type
Edge Article

Optical control of AMPA receptors using a photoswitchable quinoxaline-2,3-dione antagonist

D. M. Barber, S. Liu, K. Gottschling, M. Sumser, M. Hollmann and D. Trauner, Chem. Sci., 2017, 8, 611
DOI: 10.1039/C6SC01621A

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