title: Optical control of an ion channel gate.
abstract: The powerful optogenetic pharmacology method allows the optical control of neuronal activity by photoswitchable ligands tethered to channels and receptors. However, this approach is technically demanding, as it requires the design of pharmacologically active ligands. The development of versatile technologies therefore represents a challenging issue. Here, we present optogating, a method in which the gating machinery of an ATP-activated P2X channel was reprogrammed to respond to light. We found that channels covalently modified by azobenzene-containing reagents at the transmembrane segments could be reversibly turned on and off by light, without the need of ATP, thus revealing an agonist-independent, light-induced gating mechanism. We demonstrate photocontrol of neuronal activity by a light-gated, ATP-insensitive P2X receptor, providing an original tool devoid of endogenous sensitivity to delineate P2X signaling in normal and pathological states. These findings open new avenues to specifically activate other ion channels independently of their natural stimulus.
authors.affiliation: Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7199, Laboratoire de Conception et Application de Molécules Bioactives, Équipe de Chimie et Neurobiologie Moléculaire, F-67400 Illkirch, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Lemoine
authors.forename: Chloé
authors.initials: C
authors.lastname: Habermacher
authors.forename: Adeline
authors.initials: A
authors.lastname: Martz
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Méry
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bouquier
authors.forename: Fanny
authors.initials: F
authors.lastname: Diverchy
authors.forename: Antoine
authors.initials: A
authors.lastname: Taly
authors.forename: François
authors.initials: F
authors.lastname: Rassendren
authors.forename: Alexandre
authors.initials: A
authors.lastname: Specht
authors.forename: Thomas
authors.initials: T
authors.lastname: Grutter
mesh_terms: D000818:Animals; D001391:Azo Compounds / Q000737:chemistry*; D057809:HEK293 Cells; D006801:Humans; D015640:Ion Channel Gating / Q000235:genetics / Q000528:radiation effects*; D008027:Light; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D058469:Receptors, Purinergic P2X / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D001391:Azo Compounds; D058469:Receptors, Purinergic P2X; C009850:azobenzene
keywords: azobenzene photoswitch; purinergic receptors