Photocontrol of genetically-specified channels
How it works: The photoswitch compound has maleimide, for coupling to a cysteine, azobenzene, for changing length with light, and a ligand (quaternary ammonium), which blocks the pore of voltage-gated channels. The channel protein has a cys mutation at the precise location where the attached photoswitch can reach the pore. Photoswitching light shortens or lengthens the azobenzene, promoting or alleviating pore block.
Photocontrol of endogenous channels
How it works: Fortuitously, we discovered that some photoswitches pass into cells though large-pore channels. Once inside, they act on native voltage-gated ion channels, with no need for genetic modification. Photoswitching light shortens or lengthens the azobenzene, again promoting or alleviating pore blockade, but in this case from the cytoplasmic side.