Ligand-gated ion channels (LGICs) regulate ionic conductances into cells, thereby regulating cellular behavior. Several tools have been developed to modulate conductance and thus probe function; however, most of these indirectly target ion channels. Magnus et al. used genetic and chemical engineering to design chimeric LGICs comprising modular combinations of pharmacologically selective ligand binding domains and diverse ion-pore domains. Using this approach, they constructed LGIC-ligand pairs that are orthogonal to naturally occurring systems and used them selectively to manipulate neuron activity in mouse brains in vivo.
C. J. Magnus, P. H. Lee, D. Atasoy, H. H. Su, L. L. Looger, S. M. Sternson, Chemical and genetic engineering of selective ion channel–ligand interactions. Science 333,1292–1296 (2011). [Abstract] [Full Text]
