2. Academic Validation
  3. Lipid-independent control of endothelial and neuronal TRPC3 channels by light

Lipid-independent control of endothelial and neuronal TRPC3 channels by light

  • Chem Sci. 2019 Jan 15;10(9):2837-2842. doi: 10.1039/c8sc05536j.
Oleksandra Tiapko 1,  Niroj Shrestha 1,  Sonja Lindinger 2,  Gema Guedes de la Cruz 3,  Annarita Graziani 1,  Christiane Klec 4,  Carmen Butorac 2,  Wolfgang F Graier 4,  Helmut Kubista 5,  Marc Freichel 6,  Lutz Birnbaumer 7 8,  Christoph Romanin 2,  Toma Glasnov 3,  Klaus Groschner 1
Affiliations

Affiliations

  • 1 Gottfried Schatz Research Center - Biophysics , Medical University of Graz , Neue Stiftingtalstraße 6/D/04 , 8010 Graz , Austria . Email: klaus.groschner@medunigraz.at.
  • 2 Institute of Biophysics , University of Linz , Gruberstrasse 40/1 , 4020 Linz , Austria.
  • 3 Institute of Chemistry , University of Graz , Heinrichstraße 28/I , 8010 Graz , Austria.
  • 4 Gottfried Schatz Research Center - Molecular Biology and Biochemistry , Medical University of Graz , Neue Stiftingtalstraße 6/6 , 8010 Graz , Austria.
  • 5 Institute of Pharmacology , Medical University of Vienna , Währinger Straße 13A , 1090 Vienna , Austria.
  • 6 Pharmakologisches Institut , Universität Heidelberg , Im Neuenheimer Feld 366 , D-69120 Heidelberg , Germany.
  • 7 Neurobiology Laboratory , National Institute of Environmental Health Sciences , Research Triangle Park , North Carolina 27709 , USA.
  • 8 Institute of Biomedical Research (BIOMED) , Catholique University of Argentina , Buenos Aires C1107AZZ , Argentina.
PMID: 30997005 DOI: 10.1039/c8sc05536j
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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