Optical Control of Ligand-Gated Ion Channels

Abstract

In the vibrant field of optogenetics, optics and genetic targeting are combined to commandeer cellular functions, such as the neuronal action potential, by optically stimulating light-sensitive ion channels expressed in the cell membrane. One broadly applicable manifestation of this approach are covalently attached photochromic tethered ligands (PTLs) that allow activating ligand-gated ion channels with outstanding spatial and temporal resolution. Here, we describe all steps towards the successful development and application of PTL-gated ion channels in cell lines and primary cells. The basis for these experiments forms a combination of molecular modeling, genetic engineering, cell culture and electrophysiology. The light-gated glutamate receptor LiGluR, which consists of the PTLfunctionalized GluK2 receptor, serves as a model.

Using Computational Modeling and Experimental Synthetic Perturbations to Probe Biological Circuits

“…Recent developments in optogenetics also hold great promise as tools for synthetic manipulation of biological circuits. Optogenetics was originally developed as a method to control nerve cell activation noninvasively using light-activated ion channels [25]. Recently, additional photoreceptor domains, such as the LOV domain from A. sativa , have been engineered to control signaling molecules, providing precise temporal and spatial control of protein activation.…”