Invertebrate gamma-aminobutyric acid-gated chloride channel (iGABA-Cl) (iGABA-Cl)

The invertebrate gamma-aminobutyric acid (GABA)-gated chloride channel is a member of the Cys-loop superfamily of ligand-gated ion channels and serves as the primary mediator of inhibitory neurotransmission in the central nervous system of insects and other invertebrates (Raymond-Delpech et al., 2005, PMID: 16135011). Upon binding of the neurotransmitter GABA, the channel undergoes a conformational change that allows the influx of chloride ions, leading to hyperpolarization of the postsynaptic neuron and suppression of neuronal excitability. This receptor is a critical target for various classes of insecticides and ectoparasiticides, including phenylpyrazoles like fipronil and the newer isoxazoline class such as fluralaner (Casida & Durkin, 2013, PMID: 23356357). These compounds typically act as non-competitive antagonists by binding within the channel pore or at allosteric sites, thereby blocking chloride conductance and causing hyperexcitation, convulsions, and death in the target organism (Weber & Selzer, 2016, PMID: 27130457). Because of structural differences between invertebrate and mammalian GABA receptors, these channels offer a high degree of selective toxicity, making them invaluable in veterinary medicine for treating flea and tick infestations and in agriculture for pest control (Gassel et al., 2014, PMID: 24703460). Resistance to these drugs often arises through specific mutations in the RDL (Resistance to dieldrin) gene, which encodes the channel subunit (Ffrench-Constant et al., 2000, PMID: 10890351).

Other names

RDL receptorResistance to dieldrin receptorInvertebrate GABA receptorGABA-gated chloride channel

Non-competitive antagonism of the chloride channel pore and allosteric inhibition (IRAC Group 2 and Group 30) (Casida & Durkin, 2013, PMID: 23356357)