» Articles » PMID: 35713469

BTDAzo: A Photoswitchable TRPC5 Channel Activator

Overview
Specialty Chemistry
Date 2022 Jun 17
PMID 35713469
Authors
Affiliations
Soon will be listed here.
Abstract

Photoswitchable reagents can be powerful tools for high-precision biological control. TRPC5 is a Ca -permeable cation channel with distinct tissue-specific roles, from synaptic function to hormone regulation. Reagents giving spatiotemporally-resolved control over TRPC5 activity may be key to understanding and harnessing its biology. Here we develop the first photoswitchable TRPC5-modulator, BTDAzo, to address this goal. BTDAzo can photocontrol TRPC5 currents in cell culture, as well as controlling endogenous TRPC5-based neuronal Ca responses in mouse brain slices. BTDAzos are also the first reported azo-benzothiadiazines, an accessible and conveniently derivatised azoheteroarene with strong two-colour photoswitching. BTDAzo's ability to control TRPC5 across relevant channel biology settings makes it suitable for a range of dynamically reversible photoswitching studies in TRP channel biology, with the aim to decipher the various biological roles of this centrally important ion channel.

Citing Articles

Photoswitchable TRPC6 channel activators evoke distinct channel kinetics reflecting different gating behaviors.

Keck M, Hermann C, Lutzel K, Gudermann T, Konrad D, Mederos Y Schnitzler M iScience. 2024; 27(10):111008.

PMID: 39403196 PMC: 11472632. DOI: 10.1016/j.isci.2024.111008.


Detour to success: photoswitching indirect excitation.

Kuntze K, Isokuortti J, van der Wal J, Laaksonen T, Crespi S, Durandin N Chem Sci. 2024; 15(30):11684-11698.

PMID: 39092110 PMC: 11290455. DOI: 10.1039/d4sc02538e.


BTDAzo: A Photoswitchable TRPC5 Channel Activator.

Muller M, Niemeyer K, Urban N, Ojha N, Zufall F, Leinders-Zufall T Angew Chem Int Ed Engl. 2022; 61(36):e202201565.

PMID: 35713469 PMC: 9542918. DOI: 10.1002/anie.202201565.

References
1.
Leinders-Zufall T, Storch U, Bleymehl K, Mederos Y Schnitzler M, Frank J, Konrad D . PhoDAGs Enable Optical Control of Diacylglycerol-Sensitive Transient Receptor Potential Channels. Cell Chem Biol. 2017; 25(2):215-223.e3. DOI: 10.1016/j.chembiol.2017.11.008. View

2.
Leinders-Zufall T, Storch U, Mederos Y Schnitzler M, Ojha N, Koike K, Gudermann T . A diacylglycerol photoswitching protocol for studying TRPC channel functions in mammalian cells and tissue slices. STAR Protoc. 2021; 2(2):100527. PMC: 8121987. DOI: 10.1016/j.xpro.2021.100527. View

3.
Just S, Chenard B, Ceci A, Strassmaier T, Chong J, Blair N . Treatment with HC-070, a potent inhibitor of TRPC4 and TRPC5, leads to anxiolytic and antidepressant effects in mice. PLoS One. 2018; 13(1):e0191225. PMC: 5791972. DOI: 10.1371/journal.pone.0191225. View

4.
Bon R, Wright D, Beech D, Sukumar P . Pharmacology of TRPC Channels and Its Potential in Cardiovascular and Metabolic Medicine. Annu Rev Pharmacol Toxicol. 2021; 62:427-446. DOI: 10.1146/annurev-pharmtox-030121-122314. View

5.
Borowiak M, Nahaboo W, Reynders M, Nekolla K, Jalinot P, Hasserodt J . Photoswitchable Inhibitors of Microtubule Dynamics Optically Control Mitosis and Cell Death. Cell. 2015; 162(2):403-411. DOI: 10.1016/j.cell.2015.06.049. View