AzoCholine enables optical control of alpha 7 nicotinic acetylcholine receptors in neural networks

Arunas Damijonaitis; Johannes Broichhagen; Tatsuya Urushima; Katharina Hüll; Jatin Nagpal; Laura Laprell; Matthias Schönberger; David H. Woodmansee; Amir Rafiq; Martin P. Sumser; Wolfgang Kummer; Alexander Gottschalk; Dirk Trauner

doi:10.1021/acschemneuro.5b00030

AzoCholine enables optical control of alpha 7 nicotinic acetylcholine receptors in neural networks

Arunas Damijonaitis, Johannes Broichhagen, Tatsuya Urushima, Katharina Hüll, Jatin Nagpal, Laura Laprell, Matthias Schönberger, David H. Woodmansee, Amir Rafiq, Martin P. Sumser, Wolfgang Kummer, Alexander Gottschalk, Dirk Trauner

Chemistry

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English (US)
Pages (from-to)	701-707
Number of pages	7
Journal	ACS Chemical Neuroscience
Volume	6
Issue number	5
DOIs	https://doi.org/10.1021/acschemneuro.5b00030
State	Published - May 20 2015

Keywords

AzoCholine
BisQ
Photopharmacology
cholinergic system
nicotinic acetylcholine receptor
photochromic ligand

ASJC Scopus subject areas

Biochemistry
Physiology
Cognitive Neuroscience
Cell Biology

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10.1021/acschemneuro.5b00030

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Damijonaitis, A., Broichhagen, J., Urushima, T., Hüll, K., Nagpal, J., Laprell, L., Schönberger, M., Woodmansee, D. H., Rafiq, A., Sumser, M. P., Kummer, W., Gottschalk, A., & Trauner, D. (2015). AzoCholine enables optical control of alpha 7 nicotinic acetylcholine receptors in neural networks. ACS Chemical Neuroscience, 6(5), 701-707. https://doi.org/10.1021/acschemneuro.5b00030

Damijonaitis, A, Broichhagen, J, Urushima, T, Hüll, K, Nagpal, J, Laprell, L, Schönberger, M, Woodmansee, DH, Rafiq, A, Sumser, MP, Kummer, W, Gottschalk, A & Trauner, D 2015, 'AzoCholine enables optical control of alpha 7 nicotinic acetylcholine receptors in neural networks', ACS Chemical Neuroscience, vol. 6, no. 5, pp. 701-707. https://doi.org/10.1021/acschemneuro.5b00030

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abstract = "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.",

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doi = "10.1021/acschemneuro.5b00030",

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AU - Nagpal, Jatin

AU - Laprell, Laura

AU - Schönberger, Matthias

AU - Woodmansee, David H.

AU - Rafiq, Amir

AU - Sumser, Martin P.

AU - Kummer, Wolfgang

AU - Gottschalk, Alexander

AU - Trauner, Dirk

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AzoCholine enables optical control of alpha 7 nicotinic acetylcholine receptors in neural networks

Abstract

Keywords

ASJC Scopus subject areas

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