Hostname: page-component-586b7cd67f-r5fsc Total loading time: 0 Render date: 2024-11-23T10:35:39.911Z Has data issue: false hasContentIssue false
  • English
  • Français

Nematode ligand-gated chloride channels: an appraisal of their involvement in macrocyclic lactone resistance and prospects for developing molecular markers

Published online by Cambridge University Press:  03 July 2007

S. McCAVERA ,
T. K. WALSH  and
A. J. WOLSTENHOLME
S. McCAVERA
Affiliation:
Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK
T. K. WALSH
Affiliation:
Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK
A. J. WOLSTENHOLME*
Affiliation:
Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK
*
*Corresponding author. Tel: +44 1225 386553. Fax: +44 1225 386779. E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Summary

Ligand-gated chloride channels, including the glutamate-(GluCl) and GABA-gated channels, are the targets of the macrocyclic lactone (ML) family of anthelmintics. Changes in the sequence and expression of these channels can cause resistance to the ML in laboratory models, such as Caenorhabditis elegans and Drosophila melanogaster. Mutations in multiple GluCl subunit genes are required for high-level ML resistance in C. elegans, and this can be influenced by additional mutations in gap junction and amphid genes. Parasitic nematodes have a different complement of channel subunit genes from C. elegans, but a few genes, including avr-14, are widely present. A polymorphism in an avr-14 orthologue, which makes the subunit less sensitive to ivermectin and glutamate, has been identified in Cooperia oncophora, and polymorphisms in several subunits have been reported from resistant isolates of Haemonchus contortus. This has led to suggestions that ML resistance may be polygenic. Possible reasons for this, and its consequences for the development of molecular tests for resistance, are explored.

Keywords

Avermectinmoxidectinglutamate-gated chloride channelGABA receptorHaemonchus contortussingle nucleotide polymorphism
Type
Research Article
Information
Parasitology , Volume 134 , Special Issue 8: MARKERS FOR ANTHELMINTIC RESISTANCE , August 2007 , pp. 1111 - 1121
Copyright
Copyright © Cambridge University Press 2007

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Adelsberger, H., Lepier, A. and Dudel, J. (2000). Activation of rat recombinant α1β2γ2s GABAA receptor by the insecticide ivermectin. European Journal of Pharmacology 394, 163–170.CrossRefGoogle ScholarPubMed
Ardelli, B. F., Guerriero, S. B. and Prichard, R. K. (2006). Ivermectin imposes selection pressure on P-glycoprotein from Onchocerca volvulus: linkage disequilibrium and genotype diversity. Parasitology 132, 375–386.CrossRefGoogle ScholarPubMed
Arena, J. P., Liu, K. K., Paress, P. S. and Cully, D. F. (1992). Expression of a glutamate-activated chloride current in Xenopus oocytes injected with Caenorhabditis elegans RNA: evidence for modulation by avermectin. Molecular Brain Research 15, 339–348.CrossRefGoogle ScholarPubMed
Blackhall, W. J., Liu, H. Y., Xu, M., Prichard, R. K. and Beech, R. N. (1998 a). Selection at a P-glycoprotein gene in ivermectin- and moxidectin-selected strains of Haemonchus contortus. Molecular and Biochemical Parasitology 95, 193–201.CrossRefGoogle Scholar
Blackhall, W. J., Pouliot, J. F., Prichard, R. K. and Beech, R. N. (1998 b). Haemonchus contortus: selection at a glutamate-gated chloride channel gene in ivermectin- and moxidectin-selected strains. Experimental Parasitology 90, 42–48.CrossRefGoogle Scholar
Blackhall, W. J., Prichard, R. K. and Beech, R. N. (2003). Selection at a gamma-aminobutyric acid receptor gene in Haemonchus contortus resistant to avermectins/milbemycins. Molecular and Biochemical Parasitology 131, 137–145.CrossRefGoogle Scholar
Blaxter, M. L., De Ley, P., Garey, J. R., Liu, L. X., Scheldeman, P., Vierstrate, A., Vanfleteren, J. R., Mackey, L. Y., Dorris, M., Frisse, L. M., Vida, J. T. and Thomas, W. K. (1998). A molecular evolution framework for the phylum Nematoda. Nature, London 392, 71–75.CrossRefGoogle ScholarPubMed
Broeks, A., Jannsen, H. W. R. M., Calafat, A. and Plaster, R. H. A. (1995). A P-glycoprotein protects Caenorhabditis elegans against natural toxins. Embo Journal 14, 1858–1866.CrossRefGoogle ScholarPubMed
Buckingham, S. D., Biggin, P. C., Sattelle, B. M., Brown, L. A. and Sattelle, D. B. (2005). Insect GABA receptors: splicing, editing, and targeting by antiparasitics and insecticides. Molecular Pharmacology 68, 942–951.CrossRefGoogle ScholarPubMed
Cheeseman, C. L., Delany, N. S., Woods, D. and Wolstenholme, A. J. (2001). High-affinity ivermectin binding to recombinant subunits of the Haemonchus contortus glutamate-gated chloride channel. Molecular and Biochemical Parasitology 114, 161–168.CrossRefGoogle ScholarPubMed
Coles, G. C., Bauer, C., Borgsteede, F. H. M., Geerts, S., Klei, T. R., Taylor, M. A. and Waller, P. J. (1992). World Association for the Advancement of Veterinary Parasitology (WAAVP) Methods for the Detection of Anthelmintic Resistance in Nematodes of Veterinary Importance. Veterinary Parasitology 44, 35–44.CrossRefGoogle ScholarPubMed
Coles, G. C., Rhodes, A. C. and Wolstenholme, A. J. (2005). Rapid selection for ivermectin resistance in Haemonchus contortus. Veterinary Parasitology 129, 345–347.CrossRefGoogle ScholarPubMed
Cook, A., Aptel, N., Portillo, V., Siney, E., Sihotra, R., Holden-Dye, L. and Wolstenholme, A. J. (2006). Caenorhabditis elegans ivermectin receptors regulate locomotor behaviour and are functional orthologues of Haemonchus contortus receptors. Molecular and Biochemical Parasitology 147, 118–125.CrossRefGoogle ScholarPubMed
Cully, D. F., Vassilatis, D. K., Liu, K. K., Paress, P., Van Der Ploeg, L. H. T., Schaeffer, J. M. and Arena, J. P. (1994). Cloning of an avermectin-sensitive glutamate-gated chloride channel from Caenorhabditis elegans. Nature, London 371, 707–711.CrossRefGoogle ScholarPubMed
Cully, D. F., Wilkinson, H. and Vassilatis, D. K. (1996). Molecular biology and electrophysiology of glutamate-gated chloride channels of invertebrates. Parasitology 113, S191–S200.CrossRefGoogle ScholarPubMed
Dawson, G. R., Wafford, K. A., Smith, A., Marshall, G. R., Bayley, P. J., Schaeffer, J. M., Meinke, P. T. and Mckernan, R. M. (2000). Anticonvulsant and adverse effects of avermectin analogs in mice are mediated through the γ-aminobutyric acidA receptor. Journal of Pharmacology and Experimental Therapeutics 295, 1051–1060.Google Scholar
Delany, N. S., Laughton, D. L. and Wolstenholme, A. J. (1998). Cloning and localisation of an avermectin receptor-related subunit from Haemonchus contortus. Molecular and Biochemical Parasitology 97, 177–187.CrossRefGoogle ScholarPubMed
Dent, J. A., Davis, M. W. and Avery, L. (1997). avr-15 encodes a chloride channel subunit that mediates inhibitory glutamatergic neurotransmission and ivermectin sensitivity in Caenorhabditis elegans. EMBO Journal 16, 5867–5879.CrossRefGoogle ScholarPubMed
Dent, J. A., Smith, M. M., Vassilatic, D. K. and Avery, L. (2000). The genetics of ivermectin resistance in Caenorhabditis elegans. Proceedings of the National Academy of Sciences, USA 97, 2674–2679.CrossRefGoogle ScholarPubMed
Egerton, J. R., Suhayda, D. and Eary, C. H. (1988). Laboratory selection of Haemonchus contortus for resistance to ivermectin. Journal of Parasitology 74, 614–617.CrossRefGoogle ScholarPubMed
Eguchi, Y., Ihara, M., Ochi, E., Shibata, Y., Matsuda, K., Fushiki, S., Sugama, H., Hamasaki, Y., Niwa, H., Wada, M., Ozoe, F. and Ozoe, Y. (2006). Functional characterization of Musca glutamate- and GABA-gated chloride channels expressed independently and coexpressed in Xenopus oocytes. Insect Molecular Biology 15, 773–783.CrossRefGoogle ScholarPubMed
Eng, J. K. L., Blackhall, W. J., Osei-Atweneboana, M. Y., Bourguinat, C., Galazzo, D., Beech, R. N., Unnasch, T. R., Awadzi, K., Lubega, G. W. and Prichard, R. K. (2006). Ivermectin selection on β-tubulin: evidence in Onchocerca volvulus and Haemonchus contortus. Molecular and Biochemical Parasitology 150, 229–235.CrossRefGoogle ScholarPubMed
Feng, X.-P., Hayashi, J., Beech, R. N. and Prichard, R. K. (2002). Study of the nematode putative GABA type-A receptor subunits: evidence for modulation by ivermectin. Journal of Neurochemistry 83, 870–878.CrossRefGoogle ScholarPubMed
ffrench-Constant, R. H., Rocheleau, T. A., Steichen, J. C. and Chalmers, A. E. (1993). A point mutation in a Drosophila GABA receptor confers insecticide resistance. Nature, London 363, 449–451.CrossRefGoogle Scholar
Forrester, S. G., Hamdan, F. F., Prichard, R. K. and Beech, R. N. (1999). Cloning, sequencing, and developmental expression levels of a novel glutamate-gated chloride channel homologue in the parasitic nematode Haemonchus contortus. Biochemical and Biophysical Research Communications 254, 529–534.CrossRefGoogle ScholarPubMed
Forrester, S. G., Prichard, R. K. and Beech, R. N. (2002). A glutamate-gated chloride channel subunit from Haemonchus contortus: Expression in a mammalian cell line, ligand-binding and modulation of anthelmintic binding by glutamate. Biochemical Pharmacology 63, 1061–1068.CrossRefGoogle Scholar
Forrester, S. G., Prichard, R. K., Dent, J. A. and Beech, R. N. (2003). Haemonchus contortus: HcGluCla expressed in Xenopus oocytes forms a glutamate-gated ion channel that is activated by ibotenate and the antiparasitic drug ivermectin. Molecular and Biochemical Parasitology 129, 115–121.CrossRefGoogle ScholarPubMed
Freeman, A. S., Nghiem, C., Li, J., Ashton, F. T., Guerrero, J., Shoop, W. L. and Schad, G. A. (2003). Amphidial structure of ivermectin-resistant and -susceptible laboratory and field strains of Haemonchus contortus. Veterinary Parasitology 110, 217–226.CrossRefGoogle ScholarPubMed
Gill, J. H., Kerr, C. A., Shoop, W. L. and Lacey, E. (1998). Evidence of multiple mechanisms of avermectin resistance in Haemonchus contortus – comparison of selection protocols. International Journal for Parasitology 28, 783–790.CrossRefGoogle ScholarPubMed
Gilleard, J. S. (2006). Understanding anthelmintic resistance: the need for genomics and genetics. International Journal for Parasitology 36, 1227–1239.CrossRefGoogle ScholarPubMed
Gisselmann, G., Pusch, H., Hovemann, B. T. and Hatt, H. (2002). Two cDNAs coding for histamine-gated ion channels in D. melanogaster. Nature Neuroscience 5, 11–12.CrossRefGoogle ScholarPubMed
Hejmadi, M. V., Jagannathan, S., Delany, N. S., Coles, G. C. and Wolstenholme, A. J. (2000). L-glutamate binding sites of parasitic nematodes: an association with ivermectin resistance? Parasitology 120, 535–545.CrossRefGoogle ScholarPubMed
Holden-Dye, L. and Walker, R. J. (1990). Avermectin and avermectin derivatives are antagonists at the 4-aminobutyric acid (gaba) receptor on the somatic muscle-cells of Ascaris – is this the site of anthelmintic action? Parasitology 101, 265–271.CrossRefGoogle Scholar
Horoszok, L., Raymond, V., Sattelle, D. B. and Wolstenholme, A. J. (2001). GLC-3: a novel fipronil and BIDN-sensitive, but picrotoxinin-insensitive, L-glutamate-gated chloride channel subunit from Caenorhabditis elegans. British Journal of Pharmacology 132, 1247–1254.CrossRefGoogle ScholarPubMed
Iovchev, M. I., Kodrov, P., Wolstenholme, A. J., Pak, W. L. and Semenov, E. P. (2002). Altered drug resistance and recovery from paralysis in Drosophila melanogaster with a deficient histamine-gated chloride channel. Journal of Neurogenetics 16, 249–262.CrossRefGoogle ScholarPubMed
Jagannathan, S. (1998). Nematode inhibitory glutamate-gated chloride ion channel receptors. PhD thesis, University of Bath.Google Scholar
Jagannathan, S., Laughton, D. L., Critten, C. L., Skinner, T. M., Horoszok, L. and Wolstenholme, A. J. (1999). Ligand-gated chloride channel subunits encoded by the Haemonchus contortus and Ascaris suum orthologues of the Caenorhabditis elegans gbr-2 (avr-14) gene. Molecular and Biochemical Parasitology 103, 129–140.CrossRefGoogle ScholarPubMed
Kane, N. S., Hirschberg, B., Qian, S., Hunt, D., Thomas, B., Brochu, R., Ludmerer, S. W., Zheng, Y., Smith, M., Arena, J. P., Cohen, C. J., Schmatz, D., Warmke, J. and Cully, D. F. (2000). Drug-resistant Drosophila indicate glutamate-gated chloride channels are targets for the antiparasitics nodulosporic acid and ivermectin. Proceedings of the National Academy of Sciences, USA 97, 13949–13954.CrossRefGoogle ScholarPubMed
Kaplan, R. M., Klei, T. R., Lyons, E. T., Lester, G., Courtney, C. H., French, D. D., Tolliver, S. C., Vidyashankar, A. N. and Zhao, Y. (2004). Prevalence of anthelmintic resistant cyathostomes on horse farms. Journal of the American Veterinary Medicine Association 225, 903–910.CrossRefGoogle ScholarPubMed
Kerboeuf, D., Blackhall, W. J., Kaminsky, R. and Von Samson-Himmelstjerna, G. (2003). P-glycoprotein in helminths: function and perspectives for anthelmintic treatment and reversal of resistance. International Journal of Antimicrobial Agents 22, 332–346.CrossRefGoogle ScholarPubMed
Khakh, B. J., Procter, W. R., Dunwiddie, T. V., Labarca, C. and Lester, H. A. (1999). Allosteric control of gating and kinetics at P2X4 receptor channels. Journal of Neuroscience 19, 7289–7299.CrossRefGoogle Scholar
Krause, R. M., Buisson, B., Bertrand, S., Corringer, P. J., Galzi, J. L., Changeux, J. P. and Bertrand, D. (1998). Ivermectin: a positive allosteric effector of the α7 neuronal nicotinic acetylcholine receptor. Molecular Pharmacology 53, 283–294.CrossRefGoogle ScholarPubMed
Kwa, M. S. G., Kooyman, F. N. J., Boersma, J. H. and Roos, M. H. (1993). Effect of selection for benzimidazole resistance in Haemonchus contortus on beta-tubulin isotype-1 and isotype-2 genes. Biochemical and Biophysical Research Communications 191, 413–419.CrossRefGoogle ScholarPubMed
Kwa, M. S. G., Veenstra, J. G., Van Dujk, M. and Roos, M. H. (1995). Beta-tubulin genes from the parasitic nematode Haemonchus contortus modulate drug resistance in Caenorhabditis elegans. Journal of Molecular Biology 246, 500–510.CrossRefGoogle ScholarPubMed
Laughton, D. L., Amar, M., Thomas, P., Towner, P., Harris, P. H., Lunt, G. G. and Wolstenholme, A. J. (1994). Cloning of a putative inhibitory amino acid receptor subunit from the nematode Haemonchus contortus. Receptors and Channels 2, 155–163.Google ScholarPubMed
Le Jambre, L. F., Geoghegan, J. and Lyndal-Murphy, M. (2005). Characterization of moxidectin resistant Trichostrongylus colubriformis and Haemonchus contortus. Veterinary Parasitology 128, 83–90.CrossRefGoogle ScholarPubMed
Le Jambre, L. F., Gill, J. H., Lenane, I. J. and Baker, P. (2000). Inheritance of avermectin resistance in Haemonchus contortus. International Journal for Parasitology 30, 105–111.CrossRefGoogle ScholarPubMed
Lubega, G. W., Klein, R. D., Geary, T. G. and Prichard, R. J. (1994). Haemonchus contortus – the role of 2 beta-tubulin gene subfamilies in the resistance to benzimidazole anthelmintics. Biochemical Pharmacology 47, 1705–1715.CrossRefGoogle Scholar
Ludmerer, S. W., Warren, V. A., Williams, B. S., Zheng, Y., Hunt, D. C., Ayer, M. B., Wallace, M. A., Chaudhary, A. G., Egan, M. A., Meinke, P. T., Dean, D. C., Garcia, M. L., Cully, D. F. and Smith, M. M. (2002). Ivermectin and nodulosporic acid receptors in Drosophila melanogaster contain both γ-aminobutyric acid-gated Rdl and glutamate-gated GluClα chloride channel subunits. Biochemistry 41, 6548–6560.CrossRefGoogle Scholar
Martin, R. J., Murray, I., Robertson, A. P., Bjorn, H. and Sangster, N. (1998). Anthelmintics and ion-channels: after a puncture, use a patch. International Journal for Parasitology 28, 849–862.CrossRefGoogle ScholarPubMed
Miyazawa, A., Fujiyoshi, Y. and Unwin, N. (2003). Structure and gating mechanism of the acetylcholine receptor pore. Nature, London 423, 949–955.CrossRefGoogle ScholarPubMed
Njue, A. I., Hayashi, J., Kinne, L., Feng, X.-P. and Prichard, R. K. (2004). Mutations in the extracellular domain of glutamate-gated chloride channel α3 and β subunits from ivermectin-resistant Cooperia oncophora affect agonist sensitivity. Journal of Neurochemistry 89, 1137–1147.CrossRefGoogle ScholarPubMed
Njue, A. I. and Prichard, R. K. (2004). Genetic variability of glutamate-gated chloride channel genes in ivermectin-susceptible and -resistant strains of Cooperia oncophora. Parasitology 129, 741–751.CrossRefGoogle ScholarPubMed
Otsen, M., Hoekstra, R., Plas, M. E., Buntjer, J. B., Lenstra, J. A. and Roos, M. H. (2001). Amplified fragment length polymorphism analysis of genetic diversity of Haemonchus contortus during selection for drug resistance. International Journal for Parasitology 31, 1138–1143.CrossRefGoogle ScholarPubMed
Otsen, M., Plas, M. E., Lenstra, J. A., Roos, M. H. and Hoekstra, R. (2000). Microsatellite diversity of isolates of the parasitic nematode Haemonchus contortus. Molecular and Biochemical Parasitology 110, 69–77.CrossRefGoogle ScholarPubMed
Paiement, J. P., Prichard, R. K. and Ribeiro, P. (1999). Haemonchus contortus: characterization of a glutamate binding site in unselected and ivermectin-selected larvae and adults. Experimental Parasitology 92, 32–39.CrossRefGoogle ScholarPubMed
Pemberton, D. J., Franks, C. J., Walker, R. J. and Holden-Dye, L. (2001). Characterization of glutamate-gated chloride channels in the pharynx of wild-type and mutant Caenorhabditis elegans delineates the role of the subunit GluCl-α2 in the function of the mature receptors. Molecular Pharmacology 59, 1037–1043.CrossRefGoogle Scholar
Portillo, V., Jagannathan, S. and Wolstenholme, A. J. (2003). Distribution of glutamate-gated chloride channel subunits in the parasitic nematode Haemonchus contortus. Journal of Comparative Neurology 462, 213–222.CrossRefGoogle ScholarPubMed
Ranjan, S., Wang, G. T., Hirschlein, C. and Simkins, K. L. (2002). Selection for resistance to macrocyclic lactones by Haemonchus contortus in sheep. Veterinary Parasitology 103, 109–117.CrossRefGoogle ScholarPubMed
Rohrer, S. P., Birzin, E. T., Eary, C. H., Schaeffer, J. M. and Shoop, W. L. (1994). Ivermectin binding sites in sensitive and resistant Haemonchus contortus. Journal of Parasitology 80, 493–497.CrossRefGoogle ScholarPubMed
Sangster, N. and Dobson, R. J. (2002). Anthelmintic Resistance. In The Biology of Nematodes. Lee, D. L. (ed.), Harwood.Google Scholar
Schofield, C. M., Jenkins, A. and Harrison, N. L. (2003). A highly conserved aspartic acid residue in the signature disulfide loop of the α1 subunit is a determinant of gating in the glycine receptor. Journal of Biological Chemistry 278, 34079–34083.CrossRefGoogle ScholarPubMed
Shan, Q., Haddrill, J. L. and Lynch, J. W. (2001). Ivermectin, an unconventional agonist of the glycine receptor chloride channel. Journal of Biological Chemistry 276, 12556–12564.CrossRefGoogle ScholarPubMed
Shoop, W. L., Egerton, J. R., Eary, C. H. and Suhayda, D. (1990). Laboratory selection of a benzimidazole-resistant isolate of Trichostrongylus colubriformis for ivermectin resistance. Journal of Parasitology 76, 186–189.CrossRefGoogle ScholarPubMed
Shoop, W. L., Mrozik, H. and Fisher, M. H. (1995). Structure and activity of avermectins and milbemycins in animal health. Veterinary Parasitology 59, 139–156.CrossRefGoogle ScholarPubMed
Skinner, T. M., Bascal, Z. A., Holden-Dye, L., Lunt, G. G. and Wolstenholme, A. J. (1998). Immunocytochemical localization of a putative inhibitory amino acid receptor subunit in the parasitic nematodes Haemonchus contortus and Ascaris suum. Parasitology 117, 89–96.CrossRefGoogle ScholarPubMed
Tandon, R., Lepage, K. T. and Kaplan, R. M. (2006). Cloning and characterization of genes encoding α and β subunits of glutamate-gated chloride channel protein in Cylicocyclus nassatus. Molecular and Biochemical Parasitology 150, 46–55.CrossRefGoogle ScholarPubMed
Van Wyk, J. A., Hoste, H., Kaplan, R. M. and Besier, R. B. (2006). Targeted selective treatment for worm management – How do we sell rational programs to farmers? Veterinary Parasitology 139, 336–346.CrossRefGoogle ScholarPubMed
Van Wyk, J. A. and Malan, F. S. (1988). Resistance of field strains of Haemonchus contortus to ivermectin, closantel, rafoxanide and the benzimidazoles in South Africa. Veterinary Record 123, 226–228.CrossRefGoogle ScholarPubMed
Vassilatis, D. K., Arena, J. P., Plasterk, R. H. A., Wilkinson, H., Schaeffer, J. M., Cully, D. F. and Van Der Ploeg, L. H. T. (1997). Genetic and biochemical evidence for a novel avermectin sensitive chloride channel in C. elegans: isolation and characterisation. Journal of Biological Chemistry 272, 33167–33174.CrossRefGoogle Scholar
Von Samson-Himmelstjerna, G. and Blackhall, W. (2005). Will technology provide solutions for drug resistance in veterinary helminths? Veterinary Parasitology 132, 223–239.CrossRefGoogle ScholarPubMed
Wolstenholme, A. J., Fairweather, I., Prichard, R. K., von Samson-Himmelstjerna, G. and Sangster, N. (2004). Drug resistance in veterinary helminths. Trends in Parasitology 20, 469–476.CrossRefGoogle ScholarPubMed
Wolstenholme, A. J. and Rogers, A. T. (2005). Glutamate-gated chloride channels and the mode of action of the avermectin/milbemycin anthelmintics. Parasitology 131, S85–S96.CrossRefGoogle ScholarPubMed
Yates, D. M., Portillo, V. and Wolstenholme, A. J. (2003). The avermectin receptors of Haemonchus contortus and Caenorhabditis elegans. International Journal for Parasitology 33, 1183–1193.CrossRefGoogle ScholarPubMed
Yates, D. M. and Wolstenholme, A. J. (2004). An ivermectin-sensitive glutamate-gated chloride channel subunit from Dirofilaria immitis. International Journal for Parasitology 34, 1065–1071.CrossRefGoogle ScholarPubMed
Zhao, X. L., Salgado, V. L., Yeh, J. Z. and Narahashi, T. (2004). Kinetic and pharmacological characterization of desensitizing and non-desensitizing glutamate-gated chloride channels in cockroach neurons. Neurotoxicology 25, 967–980.CrossRefGoogle ScholarPubMed
Zheng, Y., Hirschberg, B., Yuan, J., Wang, A. P., Hunt, D. C., Ludmerer, S. W., Schmatz, D. M. and Cully, D. F. (2002). Identification of two novel Drosophila melanogaster histamine-gated chloride channel subunits expressed in the eye. Journal of Biological Chemistry 277, 2000–2005.CrossRefGoogle ScholarPubMed