title: Photochemical control of endogenous ion channels and cellular excitability.
abstract: Light-activated ion channels provide a precise and noninvasive optical means for controlling action potential firing, but the genes encoding these channels must first be delivered and expressed in target cells. Here we describe a method for bestowing light sensitivity onto endogenous ion channels that does not rely on exogenous gene expression. The method uses a synthetic photoisomerizable small molecule, or photoswitchable affinity label (PAL), that specifically targets K+ channels. PALs contain a reactive electrophile, enabling covalent attachment of the photoswitch to naturally occurring nucleophiles in K+ channels. Ion flow through PAL-modified channels is turned on or off by photoisomerizing PAL with different wavelengths of light. We showed that PAL treatment confers light sensitivity onto endogenous K+ channels in isolated rat neurons and in intact neural structures from rat and leech, allowing rapid optical regulation of excitability without genetic modification.
authors.affiliation: Department of Molecular and Cell Biology, University of California Berkeley, 121 Life Sciences Addition, Berkeley, California 94720, USA.
authors.forename: Doris L
authors.initials: DL
authors.lastname: Fortin
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Banghart
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Dunn
authors.forename: Katharine
authors.initials: K
authors.lastname: Borges
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Wagenaar
authors.forename: Quentin
authors.initials: Q
authors.lastname: Gaudry
authors.forename: Movses H
authors.initials: MH
authors.lastname: Karakossian
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Otis
authors.forename: William B
authors.initials: WB
authors.lastname: Kristan
authors.forename: Dirk
authors.initials: D
authors.lastname: Trauner
authors.forename: Richard H
authors.initials: RH
authors.lastname: Kramer
mesh_terms: D000200:Action Potentials / Q000528:radiation effects*; D000345:Affinity Labels / Q000737:chemistry; D000818:Animals; D001391:Azo Compounds / Q000737:chemistry; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D015640:Ion Channel Gating / Q000528:radiation effects*; D007865:Leeches; D009474:Neurons / Q000378:metabolism / Q000528:radiation effects; D010775:Photic Stimulation; D010777:Photochemistry; D015221:Potassium Channels / Q000378:metabolism*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D051381:Rats
chemical_list: D000345:Affinity Labels; D001391:Azo Compounds; D015221:Potassium Channels; D000644:Quaternary Ammonium Compounds; C009850:azobenzene