AzoCholine Enables Optical Control of Alpha 7 Nicotinic Acetylcholine Receptors in Neural Networks

• Published in: ACS chemical neuroscience 2015-05, Vol.6 (5), p.701-707
• Main Authors: Damijonaitis, Arunas, Broichhagen, Johannes, Urushima, Tatsuya, Hüll, Katharina, Nagpal, Jatin, Laprell, Laura, Schönberger, Matthias, Woodmansee, David H, Rafiq, Amir, Sumser, Martin P, Kummer, Wolfgang, Gottschalk, Alexander, Trauner, Dirk
• Format: Article
• Language: English
• Subjects: alpha7 Nicotinic Acetylcholine Receptor - metabolism; Animals; Azo Compounds - pharmacology; Caenorhabditis elegans; Female; HEK293 Cells; Humans; Male; Mice; Mice, Inbred C57BL; Nerve Net - drug effects; Nicotinic Agonists - pharmacology; Patch-Clamp Techniques; Quaternary Ammonium Compounds - pharmacology; Rats; Rats, Wistar; Transfection
• ISSN: 1948-7193; 1948-7193
• DOI: 10.1021/acschemneuro.5b00030

Nicotinic acetylcholine receptors (nAChRs) are essential for cellular communication in higher organisms. Even though a vast pharmacological toolset to study cholinergic systems has been developed, control of endogenous neuronal nAChRs with high spatiotemporal precision has been lacking. To address this issue, we have generated photoswitchable nAChR agonists and re-evaluated the known photochromic ligand, BisQ. Using electrophysiology, we found that one of our new compounds, AzoCholine, is an excellent photoswitchable agonist for neuronal α7 nAChRs, whereas BisQ was confirmed to be an agonist for the muscle-type nAChR. AzoCholine could be used to modulate cholinergic activity in a brain slice and in dorsal root ganglion neurons. In addition, we demonstrate light-dependent perturbation of behavior in the nematode, Caenorhabditis elegans.