Invertebrate gamma-aminobutyric acid-gated chloride receptor (iGABACl)

Invertebrate gamma-aminobutyric acid (GABA)-gated chloride receptors are pentameric ligand-gated ion channels that mediate fast inhibitory neurotransmission in the nervous systems of insects, arachnids, and nematodes [1, 2]. These receptors are members of the Cys-loop superfamily and function by opening a chloride-selective pore upon binding the neurotransmitter GABA, leading to membrane hyperpolarization and the suppression of neuronal activity [1, 3]. They are critical for regulating motor coordination, sensory processing, and behavior in invertebrates [2]. Due to their essential role and structural differences from vertebrate GABA-A receptors, they serve as primary targets for numerous insecticides and parasiticides, including phenylpyrazoles (e.g., fipronil), cyclodienes (e.g., dieldrin), and isoxazolines (e.g., fluralaner) [2, 4]. These compounds typically act as non-competitive antagonists that bind within the channel pore to block ion flow, leading to overexcitation of the nervous system and death of the organism [4, 5]. However, the development of resistance, often mediated by mutations in the Rdl (resistance to dieldrin) gene, and potential cross-reactivity with mammalian GABA receptors present significant therapeutic and environmental challenges [1, 5].

Other names

Invertebrate GABA receptorRDL receptoriGABAClGABA-gated chloride channelIonotropic GABA receptor

Non-competitive antagonism of the chloride channel pore, which blocks the inhibitory effect of GABA and leads to lethal neuronal overstimulation [2, 4, 5].