Engineering Light-Gated Ion Channels †

ABSTRACT: Ion channels are gated by a variety of stimuli, including ligands, voltage, membrane tension, temperature, and even light. Natural gates can be altered and augmented using synthetic chemistry and molecular biology to develop channels with completely new functional properties. Light-sensitive channels are particularly attractive because optical manipulation offers a high degree of spatial and temporal control. Over the last few decades, several channels have been successfully rendered responsive to light, including the nicotinic acetylcholine receptor, gramicidin A, a voltage-gated potassium channel, an ionotropic glutamate receptor, R-hemolysin, and a mechanosensitive channel. Very recently, naturally occurring lightgated cation channels have been discovered. This review covers the molecular principles that guide the engineering of light-gated ion channels for applications in biology and medicine. Ion channels control the electrical properties of cells by gating in response to a wide array of stimuli. To date, ion channels have been identified that are sensitive to changes in the concentration of ligands such as small molecules and ions, changes in membrane potential, temperature fluctuations, alterations in membrane tension, and most recently