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Insect GABA Receptors: Splicing, Editing, and Targeting by Antiparasitics and Insecticides

Steven David Buckingham, Philip Charles Biggin, Benedict Mark Sattelle, Laurence Andrew Brown and David Barry Sattelle
Molecular Pharmacology October 2005, 68 (4) 942-951; DOI: https://doi.org/10.1124/mol.105.015313
Steven David Buckingham
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Philip Charles Biggin
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Benedict Mark Sattelle
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Laurence Andrew Brown
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David Barry Sattelle
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Abstract

Ionotropic GABA receptors are abundant in both vertebrate and invertebrate nervous systems, where they mediate rapid, mostly inhibitory synaptic transmission. A GABA-gated chloride channel subunit from Drosophila melanogaster [Resistant to Dieldrin (RDL)] has been cloned, functionally expressed, and found to exhibit many aspects of the pharmacology of native, bicuculline-insensitive insect GABA receptors. RDL is the target of the commercially important insecticide fipronil. A point mutation in the channel-lining region of the RDL molecule is known to underlie most cases of resistance to insecticides acting on GABA receptors. RDL is widely distributed throughout the insect nervous system, but the subunit composition of RDL-containing in native receptors is unknown. It is possible that in some instances, RDL coexpresses with glutamate-gated chloride channel subunits. Other ionotropic receptor subunits (LCCH3 and GRD) form GABA-gated cation channels when heterologously expressed. Interest in RDL as a model ligandgated anion channel has been enhanced by the recent discovery of pre-mRNA A-to-I editing, which, together with alternative splicing, adds to the functional diversity of this GABA receptor subunit.

  • Received June 2, 2005.
  • Accepted July 18, 2005.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 68 (4)
Molecular Pharmacology
Vol. 68, Issue 4
1 Oct 2005
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OtherMINIREVIEW

Insect GABA Receptors: Splicing, Editing, and Targeting by Antiparasitics and Insecticides

Steven David Buckingham, Philip Charles Biggin, Benedict Mark Sattelle, Laurence Andrew Brown and David Barry Sattelle
Molecular Pharmacology October 1, 2005, 68 (4) 942-951; DOI: https://doi.org/10.1124/mol.105.015313

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OtherMINIREVIEW

Insect GABA Receptors: Splicing, Editing, and Targeting by Antiparasitics and Insecticides

Steven David Buckingham, Philip Charles Biggin, Benedict Mark Sattelle, Laurence Andrew Brown and David Barry Sattelle
Molecular Pharmacology October 1, 2005, 68 (4) 942-951; DOI: https://doi.org/10.1124/mol.105.015313
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  • Article
    • Abstract
    • The Insect GABA-Gated Chloride Channel Family
    • Alternative Splicing of the Rdl Gene
    • Pre-mRNA Editing of RDL
    • RDL As a Model of Native Insect GABA Receptors
    • Coassembly of RDL with Glutamate-Gated Chloride Receptor Subunits?
    • GABA-Gated Cation Channels
    • Molecular Target for Insecticides and a Point Mutation in RDL That Accounts for Resistance
    • Conclusions
    • Acknowledgments
    • Footnotes
    • References
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