With the aim of designing improved pharmacological tools to dissect the function of GIRK channels, a photo-pharmacological approach led to the development of a series of photoswitchable versions of VU0259369, a hit molecule identified in a previous thallium-flux assay based HTS [33]. The new photoswitchable modulators enabled light control of GIRK activation [34, 35]. These GIRK activating compounds, based on the photoswitchable azobenzene moiety, were named LOGO for Light-Operated GIRK channel Opener [34], and VLOGO (Visible LOGO), a red-shifted variant [35]. Both act as photochromic GIRK1-containing channel openers in the dark, and the channel inactivates upon exposure to light of 365 (LOGO) or 420 nm (VLOGO). Photoswitching of LOGO5 or VLOGO reduced neuronal excitability in rodent hippocampal neurons, and diminished the motility of zebrafish larvae in vivo (Table 1, Figure 3) [34, 35]. In 2019, Trads et al described a diazozine version of photoswitchable GIRK openers, CLOGO (Cyclic azobenzene LOGO) [36]. CLOGO has an inverted pharmacological sign (inactive in the dark and active upon light exposure) which makes it more suitable as pharmacological tool. CLOGO reduced action potential firing in
