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

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 nervous systems of insects and other invertebrates (Bloomquist, 1996). Upon binding of the neurotransmitter GABA, the channel opens to allow the influx of chloride ions, which hyperpolarizes the postsynaptic neuron and suppresses electrical activity (Buckingham et al., 2005). This receptor is a major target for several classes of insecticides and ectoparasiticides, including phenylpyrazoles like fipronil and the isoxazoline class, such as fluralaner (Casida, 2015). These drugs typically act as non-competitive antagonists that bind to the inner lining of the chloride channel pore, effectively blocking the inhibitory signal and leading to lethal hyperexcitation of the parasite's nervous system (Gassel et al., 2014). While these channels share structural homology with mammalian GABA-A receptors, distinct amino acid sequences in the binding sites provide high selectivity for invertebrate targets, minimizing host toxicity (Raymond-Delpech et al., 2005). However, the widespread use of these chemicals has led to the emergence of resistance, frequently associated with mutations in the RDL (Resistance to dieldrin) gene, such as the A302S substitution (Ffrench-Constant et al., 2000). Understanding the structural biology of these channels is essential for developing next-generation pesticides that overcome existing resistance mechanisms (Nakao, 2017).

Other names

RDL receptorResistance to dieldrin proteinInvertebrate GABA receptorGABA-gated chloride channel

Non-competitive antagonism of the chloride channel pore, blocking inhibitory neurotransmission and causing lethal hyperexcitation of the nervous system.