title: Controlling epithelial sodium channels with light using photoswitchable amilorides.
abstract: Amiloride is a widely used diuretic that blocks epithelial sodium channels (ENaCs). These heterotrimeric transmembrane proteins, assembled from β, γ and α or δ subunits, effectively control water transport across epithelia and sodium influx into non-epithelial cells. The functional role of δβγENaC in various organs, including the human brain, is still poorly understood and no pharmacological tools are available for the functional differentiation between α- and δ-containing ENaCs. Here we report several photoswitchable versions of amiloride. One compound, termed PA1, enables the optical control of ENaC channels, in particular the δβγ isoform, by switching between blue and green light, or by turning on and off blue light. PA1 was used to modify functionally δβγENaC in amphibian and mammalian cells. We also show that PA1 can be used to differentiate between δβγENaC and αβγENaC in a model for the human lung epithelium.
authors: Department of Chemistry and Center for Integrated Protein Science, Ludwig Maximilians-Universität München, Butenandtstraße 5-13 (F4.086), 81377 Munich, Germany.
authors: Matthias
authors: M
authors: Schönberger
authors: Institute of Animal Physiology, Justus Liebig University Giessen, Heinrich-Buff-Ring 26, 35392 Giessen, Germany.
authors: Mike
authors: M
authors: Althaus
authors: 1] Institute of Animal Physiology, Justus Liebig University Giessen, Heinrich-Buff-Ring 26, 35392 Giessen, Germany [2] Department of Physiology, University of Otago, PO Box 913, Dunedin 9054, New Zealand.
authors: Martin
authors: M
authors: Fronius
authors: Institute of Animal Physiology, Justus Liebig University Giessen, Heinrich-Buff-Ring 26, 35392 Giessen, Germany.
authors: Wolfgang
authors: W
authors: Clauss
authors: Department of Chemistry and Center for Integrated Protein Science, Ludwig Maximilians-Universität München, Butenandtstraße 5-13 (F4.086), 81377 Munich, Germany.
authors: Dirk
authors: D
authors: Trauner
mesh_terms: D000584:Amiloride / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D001391:Azo Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D018360:Crystallography, X-Ray; D053503:Epithelial Sodium Channels / Q000737:chemistry / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008027:Light; D008968:Molecular Conformation; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D014981:Xenopus / Q000254:growth & development
chemical_list: D001391:Azo Compounds; D053503:Epithelial Sodium Channels; D020033:Protein Isoforms; D026941:Sodium Channel Blockers; C000592315:photoamiloride-1; D000584:Amiloride