Probing ion channel structure and function using light-sensitive amino acids

Approaches to remotely control and monitor ion channel operation with light are fast expanding in the field of biophysics and neuroscience. A recent development to directly introduce light-sensitivity into proteins relies on the genetic code expansion technique by utilizing photo-sensitive unnatural amino acids (UAAs). Introduction of UAAs results in unique molecular level control, and combined with the maximal spatio-temporal resolution and poor invasiveness of light, enables direct manipulation and interrogation of ion channel functionality. Here, we review the diverse applications of light-sensitive UAAs in two superfamilies of ion channels - voltage- and ligand-gated ion channels – and summarize the existing UAA tools, their mode of action, potential, caveats, and technical considerations to illuminate ion channel structure and function.