title: Hco-LGC-38 is novel nematode cys-loop GABA receptor subunit.
abstract: We have identified and characterized a novel cys-loop GABA receptor subunit (Hco-LGC-38) from the parasitic nematode Haemonchus contortus. This subunit is present in parasitic and free-living nematodes and shares similarity to both the UNC-49 group of GABA receptor subunits from nematodes and the resistant to dieldrin (RDL) receptors of insects. Expression of the Hco-lgc-38 gene in Xenopus oocytes and subsequent electrophysiological analysis has revealed that the gene encodes a homomeric channel sensitive to GABA (EC(50) 19 μM) and the GABA analogue muscimol. The sensitivity of the Hco-LGC-38 channel to GABA is similar to reported values for the Drosophila RDL receptor whereas its lower sensitivity to muscimol is similar to nematode GABA receptors. Hco-LGC-38 is also highly sensitive to the channel blocker picrotoxin and moderately sensitive to fipronil and dieldrin. Homology modeling of Hco-LGC-38 and subsequent docking of GABA and muscimol into the binding site has uncovered several types of potential interactions with binding-site residues and overall appears to share similarity with models of other invertebrate GABA receptors.
authors.affiliation: Applied Bioscience Graduate Program, University of Ontario Institute of Technology, Oshawa, Ontario, Canada.
authors.forename: Salma Z
authors.initials: SZ
authors.lastname: Siddiqui
authors.forename: David D R
authors.initials: DD
authors.lastname: Brown
authors.forename: Michael V
authors.initials: MV
authors.lastname: Accardi
authors.forename: Sean G
authors.initials: SG
authors.lastname: Forrester
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003001:Cloning, Molecular; D004026:Dieldrin; D004594:Electrophysiology; D006189:Haemonchus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015801:Helminth Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D058446:Ligand-Gated Ion Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009118:Muscimol / Q000378:metabolism; D010802:Phylogeny; D018079:Receptors, GABA / Q000737:chemistry / Q000145:classification* / Q000235:genetics / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D014982:Xenopus laevis / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D015801:Helminth Proteins; D058446:Ligand-Gated Ion Channels; D018079:Receptors, GABA; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D004026:Dieldrin