title: Light-activated ion channels for remote control of neuronal firing.
abstract: Neurons have ion channels that are directly gated by voltage, ligands and temperature but not by light. Using structure-based design, we have developed a new chemical gate that confers light sensitivity to an ion channel. The gate includes a functional group for selective conjugation to an engineered K(+) channel, a pore blocker and a photoisomerizable azobenzene. Long-wavelength light drives the azobenzene moiety into its extended trans configuration, allowing the blocker to reach the pore. Short-wavelength light generates the shorter cis configuration, retracting the blocker and allowing conduction. Exogenous expression of these channels in rat hippocampal neurons, followed by chemical modification with the photoswitchable gate, enables different wavelengths of light to switch action potential firing on and off. These synthetic photoisomerizable azobenzene-regulated K(+) (SPARK) channels allow rapid, precise and reversible control over neuronal firing, with potential applications for dissecting neural circuits and controlling activity downstream from sites of neural damage or degeneration.
authors.affiliation: Department of Chemistry, University of California, Berkeley, California 94720, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Banghart
authors.forename: Katharine
authors.initials: K
authors.lastname: Borges
authors.forename: Ehud
authors.initials: E
authors.lastname: Isacoff
authors.forename: Dirk
authors.initials: D
authors.lastname: Trauner
authors.forename: Richard H
authors.initials: RH
authors.lastname: Kramer
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D006624:Hippocampus / Q000502:physiology; D015640:Ion Channel Gating / Q000502:physiology; D007473:Ion Channels / Q000737:chemistry / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D010775:Photic Stimulation / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014982:Xenopus laevis
chemical_list: D007473:Ion Channels