Arthropod gamma-aminobutyric acid-gated chloride channel (GABA-Cl)

Arthropod gamma-aminobutyric acid (GABA)-gated chloride channels are essential inhibitory neurotransmitter receptors in the central nervous system of insects and other arthropods (Sattelle et al., 1991). These receptors belong to the Cys-loop superfamily of ligand-gated ion channels and are typically composed of five subunits, most notably the Resistance to dieldrin (RDL) subunit, which form a chloride-selective pore (UniProt Consortium, 2024). Upon binding of GABA, the channel opens to allow chloride influx, leading to hyperpolarization and inhibition of neuronal activity. These channels are the primary targets for several major classes of insecticides, including phenylpyrazoles like fipronil and the newer isoxazolines like fluralaner (Gassel et al., 2014). These compounds typically act as non-competitive antagonists, binding within the channel pore to block chloride conductance, which causes over-excitation of the nervous system, paralysis, and death (Casida & Durkin, 2013). Because arthropod GABA receptors exhibit distinct pharmacological profiles compared to their mammalian counterparts, they provide a high degree of selective toxicity, making them ideal targets for pest control and veterinary medicine (IRAC, 2023).

Other names

RDL receptorResistance to dieldrin receptorIonotropic GABA receptorArthropod GABA receptorGABA-gated chloride channel

Non-competitive antagonism of the chloride channel pore, leading to hyperexcitation of the nervous system and death of the arthropod (Casida & Durkin, 2013).