Journal
MOLECULAR AND BIOCHEMICAL PARASITOLOGY
Volume 185, Issue 2, Pages 137-144Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.molbiopara.2012.08.004
Keywords
GABA receptor; LGC-38; Electrophysiology; Ligand-gated chloride channel; Haemonchus contortus
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Funding
- Natural Science and Engineering Research and Canadian Foundation
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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 (EC50 19 mu M) 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. (C) 2012 Elsevier B.V. All rights reserved.
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