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

Barber, David M.; Liu, Shu-An; Gottschling, Kevin; Sumser, Martin; Hollmann, Michael and Trauner, Dirk (2017): Optical control of AMPA receptors using a photoswitchable quinoxaline-2,3-dione antagonist. In: Chemical Science, Vol. 8, No. 1: pp. 611-615

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.

• Item Type: Journal article
• Form of publication: Publisher's Version
• Faculties: Chemistry and Pharmacy
• Subjects: 500 Science > 540 Chemistry
• Alliance/National Licence: This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.
• Annotation: First published online 24 Aug 2016
• Language: English