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

• Verfasst von: Tiapko, Oleksandra [VerfasserIn]
• Verfasst von: Freichel, Marc [VerfasserIn]
• Titel: Lipid-independent control of endothelial and neuronal TRPC3 channels by light
• Verf.angabe: 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
• E-Jahr: 2019
• Jahr: 15 Jan 2019
• Umfang: 6 S.
• Fussnoten: Gesehen am 27.03.2019
• Titel Quelle: Enthalten in: Chemical science
• Ort Quelle: Cambridge : RSC, 2010
• Jahr Quelle: 2019
• Band/Heft Quelle: 10(2019), 9, Seite 2837-2842
• ISSN Quelle: 2041-6539
• DOI: doi:10.1039/C8SC05536J
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 166243507X

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.