info:eu-repo/semantics/article
Lipid-independent control of endothelial and neuronal TRPC3 channels by light
Fecha
2019-01Registro en:
Tiapko, Oleksandra; Shrestha, Niroj; Lindinger, Sonja; Guedes De La Cruz, Gema; Graziani, Annarita; et al.; Lipid-independent control of endothelial and neuronal TRPC3 channels by light; Royal Society of Chemistry; Chemical Science; 10; 9; 1-2019; 2837-2842
2041-6520
2041-6539
CONICET Digital
CONICET
Autor
Tiapko, Oleksandra
Shrestha, Niroj
Lindinger, Sonja
Guedes De La Cruz, Gema
Graziani, Annarita
Klec, Christiane
Butorac, Carmen
Graier, Wolfgang. F.
Kubista, Helmut
Freichel, Marc
Birnbaumer, Lutz
Romanin, Christoph
Glasnov, Toma
Groschner, Klaus
Resumen
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.