Arthropod GABA-gated chloride channel (RDL)

The arthropod GABA-gated chloride channel is a pentameric ligand-gated ion channel (pLGIC) that serves as the primary mediator of fast inhibitory neurotransmission in the central nervous system of insects and other arthropods [1.1.1, 1.2.2]. It is a member of the Cys-loop receptor superfamily and is most commonly represented by the RDL (Resistance to dieldrin) subunit, which can form functional homomeric or heteromeric channels [1.2.1, 1.3.1]. This receptor is a critical target for numerous insecticide classes, including cyclodienes (e.g., dieldrin), phenylpyrazoles (e.g., fipronil), and the newer isoxazolines (e.g., fluralaner) [1.2.2, 1.3.3]. These compounds typically act as non-competitive antagonists by binding within the channel pore to block chloride ion conductance, resulting in uncontrolled neuronal hyperexcitation, convulsions, and death of the organism [1.3.2, 1.4.2]. While it shares structural homology with mammalian GABA-A receptors, significant pharmacological differences exist, which are exploited to achieve high insecticidal selectivity and safety for vertebrate hosts [1.4.1]. Resistance to these insecticides often arises through specific point mutations in the RDL gene, such as the substitution of alanine at position 302, which reduces the binding affinity of the antagonists [1.1.1, 1.3.3].

Other names

RDLResistance to dieldrinGABA-receptor-chloride-channel complexGRCCInsect GABA receptorGABA-gated chloride channel (GABACl)Arthropod GABA-A receptor

Non-competitive antagonism of the chloride channel pore; stabilization of non-conducting receptor conformations; inhibition of GABA-induced inhibitory postsynaptic potentials.