AzoCholine Enables Optical Control of Alpha 7 Nicotinic Acetylcholine Receptors in Neural Networks.
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.
†Department of Chemistry and Pharmacology, Ludwig-Maximilians-Universität München, Center of Integrated Protein Science Munich, Munich D-81377, Germany.
Arunas
A
Damijonaitis
†Department of Chemistry and Pharmacology, Ludwig-Maximilians-Universität München, Center of Integrated Protein Science Munich, Munich D-81377, Germany.
Johannes
J
Broichhagen
†Department of Chemistry and Pharmacology, Ludwig-Maximilians-Universität München, Center of Integrated Protein Science Munich, Munich D-81377, Germany.
Tatsuya
T
Urushima
†Department of Chemistry and Pharmacology, Ludwig-Maximilians-Universität München, Center of Integrated Protein Science Munich, Munich D-81377, Germany.
Katharina
K
Hüll
‡Buchmann Institute for Molecular Life Sciences, Institute of Biochemistry, Johann Wolfgang Goethe-Universität, Frankfurt D-60438, Germany.
Jatin
J
Nagpal
†Department of Chemistry and Pharmacology, Ludwig-Maximilians-Universität München, Center of Integrated Protein Science Munich, Munich D-81377, Germany.
Laura
L
Laprell
†Department of Chemistry and Pharmacology, Ludwig-Maximilians-Universität München, Center of Integrated Protein Science Munich, Munich D-81377, Germany.
Matthias
M
Schönberger
†Department of Chemistry and Pharmacology, Ludwig-Maximilians-Universität München, Center of Integrated Protein Science Munich, Munich D-81377, Germany.
David H
DH
Woodmansee
§Institute for Anatomy and Cell Biology, Justus-Liebig-Universität, German Center for Lung Research, Giessen D-35385, Germany.
Amir
A
Rafiq
†Department of Chemistry and Pharmacology, Ludwig-Maximilians-Universität München, Center of Integrated Protein Science Munich, Munich D-81377, Germany.
Martin P
MP
Sumser
§Institute for Anatomy and Cell Biology, Justus-Liebig-Universität, German Center for Lung Research, Giessen D-35385, Germany.
Wolfgang
W
Kummer
‡Buchmann Institute for Molecular Life Sciences, Institute of Biochemistry, Johann Wolfgang Goethe-Universität, Frankfurt D-60438, Germany.
Alexander
A
Gottschalk
†Department of Chemistry and Pharmacology, Ludwig-Maximilians-Universität München, Center of Integrated Protein Science Munich, Munich D-81377, Germany.
Dirk
D
Trauner
D000818:Animals; D001391:Azo Compounds / Q000494:pharmacology*; D017173:Caenorhabditis elegans; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009415:Nerve Net / Q000187:drug effects*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014162:Transfection; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000378:metabolism*
D001391:Azo Compounds; C000605557:AzoCholine; D018722:Nicotinic Agonists; D000644:Quaternary Ammonium Compounds; D064569:alpha7 Nicotinic Acetylcholine Receptor
AzoCholine; BisQ; Photopharmacology; cholinergic system; nicotinic acetylcholine receptor; photochromic ligand