Fig. 1.

Photochromic ligands (PCLs) for K⁺ channels. (a) Schematic representation of a PCL containing a central photoisomerizable azobenzene core, a ligand head, and a tail. Isomerization between the elongated trans and the bent cis azobenzenes occurs upon irradiation with different wavelengths of light (hν1 and hν2). The cis isomer is of higher energy and can relax back to trans spontaneously in the dark (Δ). (b) Architectural features of K⁺ channels. K⁺ channels are tetrameric proteins but only two subunits are shown for clarity. The ion path has distinct elements: an external filter that is highly selective for K⁺ ions, a central vestibule, and an intracellular gate. Voltage-gated K⁺ channels have an additional voltage-sensing domain that opens the gate upon membrane depolarization (not depicted here). (c) Schematic view of a photochromic blocker for K⁺ channels that blocks the channel in the trans form (inner vestibule) and unbinds in the cis form. (d) Examples of PCLs for K⁺ channels: AAQ acrylamid azobenzene quaternary ammonium, BzAQ benzylamide azobenzene quaternary ammonium, PrAQ propyl azobenzene quaternary ammonium, and QAQ quaternary ammonium azobenzene quaternary ammonium