title: Optical control of neuronal activity using a light-operated GIRK channel opener (LOGO).
abstract: G-protein coupled inwardly rectifying potassium channels (GIRKs) are ubiquitously expressed throughout the human body and are an integral part of inhibitory signal transduction pathways. Upon binding of Gβγsubunits released from G-protein coupled receptors (GPCRs), GIRK channels open and reduce the activity of excitable cells via hyperpolarization. As such, they play a role in cardiac output, the coordination of movement and cognition. Due to their involvement in a multitude of pathways, the precision control of GIRK channels is an important endeavour. Here, we describe the development of the photoswitchable agonistLOGO(theLightOperatedGIRK-channelOpener), which activates GIRK channels in the dark and is rapidly deactivated upon exposure to long wavelength UV irradiation.LOGOis the first K+channel opener and selectively targets channels that contain the GIRK1 subunit. It can be used to optically silence action potential firing in dissociated hippocampal neurons andLOGOexhibits activityin vivo, controlling the motility of zebrafish larvae in a light dependent fashion. We envisage thatLOGOwill be a valuable research tool to dissect the function of GIRK channels from other GPCR dependent signalling pathways.
authors.affiliation: Department of Chemistry and Center for Integrated Protein Science, Ludwig Maximilians University Munich, Butenandtstraße 5-13, 81377 Munich, Germany.
authors.forename: David M
authors.initials: DM
authors.lastname: Barber
authors.affiliation: Department of Chemistry and Center for Integrated Protein Science, Ludwig Maximilians University Munich, Butenandtstraße 5-13, 81377 Munich, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schönberger
authors.affiliation: Max Planck Institute of Neurobiology, Am Klopferspitz 18, 82152 Martinsried, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Burgstaller
authors.affiliation: Department of Molecular and Cell Biology and Helen Wills Neuroscience Institute, University of California, Berkeley, California, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Levitz
authors.affiliation: Department of Pharmacology and Institute of Chemical Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
authors.forename: C David
authors.initials: CD
authors.lastname: Weaver
authors.affiliation: Department of Molecular and Cell Biology and Helen Wills Neuroscience Institute, University of California, Berkeley, California, USA; Physical Bioscience Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.
authors.forename: Ehud Y
authors.initials: EY
authors.lastname: Isacoff
authors.affiliation: Max Planck Institute of Neurobiology, Am Klopferspitz 18, 82152 Martinsried, Germany.
authors.forename: Herwig
authors.initials: H
authors.lastname: Baier
authors.affiliation: Department of Chemistry and Center for Integrated Protein Science, Ludwig Maximilians University Munich, Butenandtstraße 5-13, 81377 Munich, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Trauner