title: Identification of two novel Drosophila melanogaster histamine-gated chloride channel subunits expressed in the eye.
abstract: Histamine has been shown to play a role in arthropod vision; it is the major neurotransmitter of arthropod photoreceptors. Histamine-gated chloride channels have been identified in insect optic lobes. We report the first isolation of cDNA clones encoding histamine-gated chloride channel subunits from the fruit fly Drosophila melanogaster. The encoded proteins, HisCl1 and HisCl2, share 60% amino acid identity with each other. The closest structural homologue is the human glycine alpha3 receptor, which shares 45 and 43% amino acid identity respectively. Northern hybridization analysis suggested that hisCl1 and hisCl2 mRNAs are predominantly expressed in the insect eye. Oocytes injected with in vitro transcribed RNA, encoding either HisCl1 or HisCl2, produced substantial chloride currents in response to histamine but not in response to GABA, glycine, and glutamate. The histamine sensitivity was similar to that observed in insect laminar neurons. Histamine-activated currents were not blocked by picrotoxinin, fipronil, strychnine, or the H2 antagonist cimetidine. Co-injection of both hisCl1 and hisCl2 RNAs resulted in expression of a histamine-gated chloride channel with increased sensitivity to histamine, demonstrating coassembly of the subunits. The insecticide ivermectin reversibly activated homomeric HisCl1 channels and, more potently, HisCl1 and HisCl2 heteromeric channels.
authors.affiliation: Merck Research Laboratories, Merck and Co., Inc., Rahway, New Jersey 07065, USA.
authors.forename: Yingcong
authors.initials: Y
authors.lastname: Zheng
authors.forename: Birgit
authors.initials: B
authors.lastname: Hirschberg
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Yuan
authors.forename: Alice P
authors.initials: AP
authors.lastname: Wang
authors.forename: David C
authors.initials: DC
authors.lastname: Hunt
authors.forename: Steven W
authors.initials: SW
authors.lastname: Ludmerer
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Schmatz
authors.forename: Doris F
authors.initials: DF
authors.lastname: Cully
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018118:Chloride Channels / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D017931:DNA Primers; D004331:Drosophila melanogaster; D005123:Eye / Q000378:metabolism*; D006632:Histamine / Q000502:physiology*; D015640:Ion Channel Gating / Q000502:physiology*; D008969:Molecular Sequence Data; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid
chemical_list: D018118:Chloride Channels; D017931:DNA Primers; D006632:Histamine