Insect gamma-aminobutyric acid receptor (iGABAR) (iGABAR)

The insect gamma-aminobutyric acid (GABA) receptor is a ligand-gated ion channel that mediates the majority of inhibitory neurotransmission in the insect central nervous system (Hosie et al., 1997). It belongs to the Cys-loop receptor superfamily and is typically composed of five subunits arranged around a central chloride-conducting pore, with the Resistance to dieldrin (RDL) subunit being the most prominent (Ffrench-Constant et al., 1993). Upon the binding of GABA, the receptor undergoes a conformational change that opens the pore, allowing chloride ions to enter the neuron and cause hyperpolarization, thereby dampening neuronal excitability (Bloomquist, 2003). This receptor is a critical target for several major classes of insecticides, including phenylpyrazoles like fipronil and the newer isoxazolines such as fluralaner (Gassel et al., 2014). These compounds act as non-competitive antagonists by binding to an allosteric site within the channel pore, effectively blocking chloride conductance and leading to lethal hyperexcitation of the insect's nervous system (Casida & Durkin, 2013). While these receptors share structural similarities with mammalian GABA-A receptors, significant sequence divergence allows for high insecticidal selectivity, which is exploited in both agricultural pest management and veterinary treatments for ectoparasites (Sattelle et al., 2008). Mutations in the RDL gene, particularly at the alanine 302 position, are well-documented biomarkers for insecticide resistance in various pest species (Ffrench-Constant, 2013).

Other names

RDL receptor (Ffrench-Constant et al., 1993)Resistance to dieldrin receptorGABA-gated chloride channel (Hosie et al., 1997)Ionotropic GABA receptorGABA-A-like receptor

Non-competitive antagonism of the GABA-gated chloride channel (IRAC Group 2 and 30) (Casida & Durkin, 2013)