Lipid-independent control of endothelial and neuronal TRPC3 channels by light
| Autor: | Annarita Graziani, Lutz Birnbaumer, Christoph Romanin, Toma N. Glasnov, Niroj Shrestha, Gema Guedes de la Cruz, Sonja Lindinger, Carmen Butorac, Helmut Kubista, Wolfgang F. Graier, Marc Freichel, Christiane Klec, Oleksandra Tiapko, Klaus Groschner |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Neuronal firing
010402 general chemistry 01 natural sciences FARMACOLOGIA TRPC3 LIPIDOS purl.org/becyt/ford/1 [https] Ciencias Biológicas Biología Celular Microbiología purl.org/becyt/ford/1.6 [https] TRPC CELULAS Photoswitch 010405 organic chemistry Chemistry Lipid metabolism General Chemistry LUZ Cell function 0104 chemical sciences 3. Good health Cell biology FISIOLOGIA 13. Climate action CIENCIAS NATURALES Y EXACTAS |
| Zdroj: | CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET Chemical Science Chemical Science. 2019;10(9):2837-2842 Repositorio Institucional (UCA) Pontificia Universidad Católica Argentina instacron:UCA |
| Popis: | A new photochromic ligand enables high precision control over native TRPC channels. 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. |
| Databáze: | OpenAIRE |
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