Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Tiapko, O; Shrestha, N; Lindinger, S; Guedes de la Cruz, G; Graziani, A; Klec, C; Butorac, C; Graier, WF; Kubista, H; Freichel, M; Birnbaumer, L; Romanin, C; Glasnov, T; Groschner, K.
Lipid-independent control of endothelial and neuronal TRPC3 channels by light.
Chem Sci. 2019; 10(9):2837-2842 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG


Autor/innen der Med Uni Graz:
Graier Wolfgang
Graziani Annarita
Groschner Klaus
Klec Christiane
Shrestha Niroj
Tiapko Oleksandra

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Number of Figures: 4
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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.

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