title: A novel chloride channel in Drosophila melanogaster is inhibited by protons.
abstract: A systematic analysis of the Drosophila genome data reveals the existence of pHCl, a novel member of ligand-gated ion channel subunits. pHCl shows nearly identical similarity to glutamate-, glycine-, and histamine-gated ion channels, does however not belong to any of these ion channel types. We identified three different sites, where splicing generates multiple transcripts of the pHCl mRNA. The pHCl is expressed in Drosophila embryo, larvae, pupae, and the adult fly. In embryos, in situ hybridization detected pHCl in the neural cord and the hindgut. Functional expression of the three different splice variants of pHCl in oocytes of Xenopus laevis and Sf9 cells induces a chloride current with a linear current-voltage relationship that is inhibited by extracellular protons and activated by avermectins in a pH-dependent manner. Further, currents through pHCl channels were induced by a raise in temperature. Our data give genetic and electrophysiological evidence that pHCl is a member of a new branch of ligand-gated ion channels in invertebrates with, however, a hitherto unique combination of pharmacological and biophysical properties.
authors.affiliation: Bayer AG, Bayer Technology Services GmbH, 51368 Leverkusen, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Schnizler
authors.forename: Beate
authors.initials: B
authors.lastname: Saeger
authors.forename: Carsten
authors.initials: C
authors.lastname: Pfeffer
authors.forename: Alexander
authors.initials: A
authors.lastname: Gerbaulet
authors.forename: Ulrich
authors.initials: U
authors.lastname: Ebbinghaus-Kintscher
authors.forename: Christoph
authors.initials: C
authors.lastname: Methfessel
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Franken
authors.forename: Klaus
authors.initials: K
authors.lastname: Raming
authors.forename: Christian H
authors.initials: CH
authors.lastname: Wetzel
authors.forename: Arunesh
authors.initials: A
authors.lastname: Saras
authors.forename: Hermann
authors.initials: H
authors.lastname: Pusch
authors.forename: Hanns
authors.initials: H
authors.lastname: Hatt
authors.forename: Günter
authors.initials: G
authors.lastname: Gisselmann
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D007814:Larva / Q000378:metabolism; D008564:Membrane Potentials / Q000502:physiology; D008969:Molecular Sequence Data; D009865:Oocytes; D011522:Protons; D011679:Pupa / Q000378:metabolism; D018411:Spodoptera; D014981:Xenopus
chemical_list: D018118:Chloride Channels; D011522:Protons