Lipid-independent control of endothelial and neuronal TRPC3 channels by light (original) (raw)
Niroj Shrestha, 
‡a Sonja Lindinger,b Gema Guedes de la Cruz,c Annarita Graziani,a Christiane Klec, d Carmen Butorac,b Wolfgang. F. Graier, d Helmut Kubista,e Marc Freichel,f Lutz Birnbaumer, gh Christoph Romanin, b Toma Glasnov c and Klaus Groschner *a
* Corresponding authors
a Gottfried Schatz Research Center – Biophysics, Medical University of Graz, Neue Stiftingtalstraße 6/D/04, 8010 Graz, Austria
E-mail: klaus.groschner@medunigraz.at
b Institute of Biophysics, University of Linz, Gruberstrasse 40/1, 4020 Linz, Austria
c Institute of Chemistry, University of Graz, Heinrichstraße 28/I, 8010 Graz, Austria
d Gottfried Schatz Research Center – Molecular Biology and Biochemistry, Medical University of Graz, Neue Stiftingtalstraße 6/6, 8010 Graz, Austria
e Institute of Pharmacology, Medical University of Vienna, Währinger Straße 13A, 1090 Vienna, Austria
f Pharmakologisches Institut, Universität Heidelberg, Im Neuenheimer Feld 366, D-69120 Heidelberg, Germany
g Neurobiology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
h Institute of Biomedical Research (BIOMED), Catholique University of Argentina, Buenos Aires C1107AZZ, Argentina
Abstract
Lipid-gated TRPC channels are highly expressed in cardiovascular and neuronal tissues. Exerting precise pharmacological control over their activity in native cells is expected to serve as a basis for the development of novel therapies. Here we report on a new photopharmacological tool that enables manipulation of TRPC3 channels by light, in a manner independent of lipid metabolism and with higher temporal precision than lipid photopharmacology. Using the azobenzene photoswitch moiety, we modified GSK1702934A to generate light-controlled TRPC agonists. We obtained one light-sensitive molecule (OptoBI-1) that allows us to exert efficient, light-mediated control over TRPC3 activity and the associated cellular Ca2+ signaling. OptoBI-1 enabled high-precision, temporal control of TRPC3-linked cell functions such as neuronal firing and endothelial Ca2+ transients. With these findings, we introduce a novel photopharmacological strategy to control native TRPC conductances.
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Article information
DOI
https://doi.org/10.1039/C8SC05536J
Article type
Edge Article
Submitted
11 Dec 2018
Accepted
09 Jan 2019
First published
15 Jan 2019
This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry
Download Citation
Chem. Sci., 2019,10, 2837-2842
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Lipid-independent control of endothelial and neuronal TRPC3 channels by light
O. Tiapko, N. Shrestha, S. Lindinger, G. Guedes de la Cruz, A. Graziani, C. Klec, C. Butorac, Wolfgang. F. Graier, H. Kubista, M. Freichel, L. Birnbaumer, C. Romanin, T. Glasnov and K. Groschner,Chem. Sci., 2019, 10, 2837DOI: 10.1039/C8SC05536J
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