Abstract
Parasitic nematode infection of humans and livestock is a major problem globally. Attempts to control nematode populations have led to the development of several classes of anthelmintic, which target cys-loop ligand-gated ion channels. Unlike the vertebrate nervous system, the nematode nervous system possesses a large and diversified array of ligand-gated chloride channels that comprise key components of the inhibitory neurotransmission system. In particular, cys-loop GABA receptors have evolved to play many fundamental roles in nematode behaviour such as locomotion. Analysis of the genomes of several free-living and parasitic nematodes suggests that there are several groups of cys-loop GABA receptor subunits that, for the most part, are conserved among nematodes. Despite many similarities with vertebrate cys-loop GABA receptors, those in nematodes are quite distinct in sequence similarity, subunit composition and biological function. With rising anthelmintic resistance in many nematode populations worldwide, GABA receptors should become an area of increased scientific investigation in the development of the next generation of anthelmintics.
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Abbreviations
- GABA:
-
γ-Aminobutyric acid
- LGCC:
-
Ligand-gated chloride channels
- PTX:
-
Picrotoxin
- RDL:
-
Resistance to dieldrin
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Acknowledgments
This research was funded by grants from NSERC and the Canadian Foundation for Innovation to SGF. MVA is a recipient of the Irma H. Bauer Fellowship and G. Rutherford Caverhill Fellowship (McGill University). We thank an anonymous reviewer for comments and suggestions on the manuscript.
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Accardi, M.V., Beech, R.N. & Forrester, S.G. Nematode cys-loop GABA receptors: biological function, pharmacology and sites of action for anthelmintics. Invert Neurosci 12, 3–12 (2012). https://doi.org/10.1007/s10158-012-0129-6
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DOI: https://doi.org/10.1007/s10158-012-0129-6