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

SHRESTHA, NIROJ; GRAZIANI, ANNARITA; GRAIER, WOLFGANG. F.; BIRNBAUMER, LUTZ; GROSCHNER, KLAUS; TIAPKO, OLEKSANDRA; GUEDES DE LA CRUZ, GEMA; BUTORAC, CARMEN; FREICHEL, MARC; GLASNOV, TOMA; LINDINGER, SONJA; KLEC, CHRISTIANE; KUBISTA, HELMUT; ROMANIN, CHRISTOPH

Chemical Science

Royal Society of Chemistry

Año: 2019 vol. 10 p. 2837 - 2842

2041-6520

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.