Background: γ-Aminobutyric acid (GABA) receptors play a central role in fast inhibitory
neurotransmission in insects. Several classes of insecticides targeting insect GABA-gated
chloride channels have been developed. The important resistant to dieldrin GABA receptor subunit
(RDL) has been used to investigate insecticide sites of action using radioligands, electrophysiology
and site-directed mutagenesis. Although this important subunit readily forms robust functional
homomeric receptors when expressed, alternative splicing and RNA A-to-I editing can generate
diverse forms of the receptor.
Methods: We have reviewed studies on native and recombinant insect GABA-gated chloride
channels, their interactions with ligands acting at orthosteric and allosteric sites and their interactions
with insecticides. Since some GABA receptor modulators act on L-glutamate-gated chloride
channels, some comparisons are included.
Results: The actions on GABA-gated chloride channels of polychlorocycloalkanes, cyclodienes,
macrocyclic lactones, phenylpyrazoles, isoxazolines, and metadiamides are described and the
mechanisms of action of members of these insecticide classes are addressed. Mutations that lead
to resistance are discussed as they can be important in developing field diagnostic tests. Toxicity
issues relating to insecticides targeting GABA-gated chloride channels are also addressed.
An overview of all major insecticide classes targeting insect GABA-gated chloride
channels has enhanced our understanding of these important receptors and their insecticide binding
sites. However, the subunit composition of native GABA receptors remains unknown and studies
to clarify this are needed. Also, the precise sites of action of the recently introduced isoxazolines
and meta-diamides will be of interest to pursue.