BTDAzo: A Photoswitchable TRPC5 Channel Activator**

Abstract

Photoswitchable reagents can be powerful tools for high-precision biological control. TRPC5 is a Ca 2 + -permeable cation channel with distinct tissuespecific 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 2 + responses in mouse brain slices. BTDAzos are also the first reported azobenzothiadiazines, 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.