Optical control of GIRK channels using visible light

Abstract

G-protein coupled inwardly rectifying potassium (GIRK) channels are an integral part of inhibitory signal transduction pathways, reducing the activity of excitable cells via hyperpolarization. They play crucial roles in processes such as cardiac output, cognition and the coordination of movement. Therefore, the precision control of GIRK channels is of critical importance. Here, we describe the development of the azobenzene containing molecule VLOGO (Visible Light Operated GIRK channel Opener), which activates GIRK channels in the dark and is promptly deactivated when illuminated with green light. VLOGO is a valuable addition to the existing tools for the optical control of GIRK channels as it circumvents the need to use potentially harmful UV irradiation. We therefore believe that VLOGO will be a useful research tool for studying GIRK channels in biological systems.

Thermodynamically Stable, Photoreversible Pharmacology in Neurons with One‐ and Two‐Photon Excitation

“…After 2 additional hours, a second cell was loaded with the same stock solution of cis ‐ 1 and exhibited the same pattern of response as the first cell (Figure a). These results are in stark contrast to the only other 4FAB probe tested with neurons in which no cis thermal stability was observed . The solution used for cell filling was then frozen for 2 days, thawed and used for a similar physiological experiment, with identical results (Figure a).…”

“…Given its excellent photochemical properties, there have been surprisingly few applications of the 4FAB chromophore, with the only neurobiological application unexpectedly showing no thermodynamic stability of the cis configuration with cells. In contrast, our work firmly establishes that the superb thermal stability of cis ‐4FAB is preserved inside cells, and can be used for photoswitching for multiple cycles of two‐color, wavelength independent excitation in living cells using visible light.…”

Hole Catalysis as a General Mechanism for Efficient and Wavelength-Independent Z → E Azobenzene Isomerization

“…Our method is generally applicable to the entire family of azobenzene switches, does not require expensive equipment, and allows the reliable and efficient operation of these photoswitches by using red light with quantum efficiencies up to 200%. bond, 17 thus making them more amenable to oxidation (lower oxidation potential) than to reduction (higher reduction potential). However, unlike the one-electron reduction of azobenzene, which is reversible, with few exceptions, the one-electron oxidation is not reversible and as a result has not been extensively studied.…”

Sign Inversion in Photopharmacology: Incorporation of Cyclic Azobenzenes in Photoswitchable Potassium Channel Blockers and Openers

“…Forschungsartikel they are associated with numerous neurological and cardiovascular (patho-)physiological conditions. [47,48] We envisioned that our previous photoswitchable GIRK-activator,t ermed LOGO [49,50] (Figure 4a), would be asuitable candidate for sign inversion because it behaves as ap otent agonist in the dark (trans-isomer), whilst the cis-isomer is significantly less active.T he same was true for ar edshifted tetrafluoro-derivative that operated with visible light and was named VLOGO [51] (Figure 4a). Substitution of the regular azobenzene or tetrafluoro azobenzene in these compounds with ad iazocine afforded the Cyclic azobenzene Light Operated GIRK channel Opener (CLOGO), the structure and basic switching behavior of which is shown in Figure 4b.…”