Lipid-independent control of endothelial and neuronal TRPC3 channels by light
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 m...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
15 Jan 2019
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| In: |
Chemical science
Year: 2019, Volume: 10, Issue: 9, Pages: 2837-2842 |
| ISSN: | 2041-6539 |
| DOI: | 10.1039/C8SC05536J |
| Online Access: | Verlag, Volltext: https://doi.org/10.1039/C8SC05536J Verlag, Volltext: https://pubs.rsc.org/en/content/articlelanding/2019/sc/c8sc05536j 
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| Author Notes: | Oleksandra Tiapko, Niroj Shrestha, Sonja Lindinger, Gema Guedes de la Cruz, Annarita Graziani, Christiane Klec, Carmen Butorac, Wolfgang F. Graier, Helmut Kubista, Marc Freichel, Lutz Birnbaumer, Christoph Romanin, Toma Glasnov and Klaus Groschner |
| Summary: | 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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| Item Description: | Gesehen am 27.03.2019 |
| Physical Description: | Online Resource |
| ISSN: | 2041-6539 |
| DOI: | 10.1039/C8SC05536J |