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

• Autores: 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
• Año de publicación: 2019
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Chemical Science. 2019;10(9):2837-2842
• Materia: LIPIDOS; FARMACOLOGIA; FISIOLOGIA; CELULAS; LUZ
• Institución: Pontificia Universidad Católica Argentina

Fil: Tiapko, Oleksandra. Medical University of Graz. Gottfried Schatz Research Center Biophysics; Austria
Fil: Shrestha, Niroj. Medical University of Graz. Gottfried Schatz Research Center Biophysics; Austria
Fil: Lindinger, Sonja. University of Linz. Institute of Biophysics; Austria
Fil: Guedes de la Cruz, Gema. University of Graz. Institute of Chemistry; Austria
Fil: Graziani, Annarita. Medical University of Graz. Gottfried Schatz Research Center Biophysics; Austria
Fil: Klec, Christiane. Medical University of Graz. Gottfried Schatz Research Center Molecular Biology and Biochemistry; Austria
Fil: Butorac, Carmen. Medical University of Graz. Gottfried Schatz Research Center Biophysics; Austria
Fil: Graier, Wolfgang F. Medical University of Graz. Gottfried Schatz Research Center Molecular Biology and Biochemistry; Austria
Fil: Kubista, Helmut. Medical University of Vienna. Institute of Pharmacology; Austria
Fil: Freichel, Marc. Universität Heidelberg. Pharmakologisches Institut; Alemania
Fil: Birnbaumer, Lutz. Research Triangle Park. National Institute of Environmental Health Sciences. Neurobiology Laboratory; Estados Unidos
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Romanin, Christoph. University of Linz. Institute of Biophysics; Austria
Fil: Glasnov, Toma. University of Graz. Institute of Chemistry; Austria
Fil: Groschner, Klaus. Medical University of Graz. Gottfried Schatz Research Center Biophysics; Austria
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.