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 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.Fil: Tiapko, Oleksandra. Medical University of Graz; AustriaFil: Shrestha, Niroj. Medical University of Graz; AustriaFil: Lindinger, Sonja. University Linz; AustriaFil: Guedes De La Cruz, Gema. University Of Graz.; AustriaFil: Graziani, Annarita. Medical University of Graz; AustriaFil: Klec, Christiane. University Of Graz.; AustriaFil: Butorac, Carmen. University Linz; AustriaFil: Graier, Wolfgang. F.. University Of Graz.; AustriaFil: Kubista, Helmut. No especifíca;Fil: Freichel, Marc. Universität Heidelberg; AlemaniaFil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Romanin, Christoph. University Linz; AustriaFil: Glasnov, Toma. Graz University Of Technology.; AustriaFil: Groschner, Klaus. Graz University Of Technology.; Austri