Gamma-aminobutyric acid-gated chloride channel subunit RDL (RDL) (RDL)

Gamma-aminobutyric acid-gated chloride channel subunit RDL (RDL) is a critical component of the inhibitory neurotransmitter system in the central nervous system of arthropods, including ticks and various insect pests (Ffrench-Constant, 1993). As a member of the Cys-loop ligand-gated ion channel superfamily, it forms homomeric or heteromeric pentameric channels that mediate fast inhibitory synaptic transmission by conducting chloride ions upon GABA binding (Casida & Durkin, 2013). This target is of immense pharmacological importance as it is the site of action for major classes of insecticides and acaricides, such as phenylpyrazoles (e.g., fipronil) and the newer isoxazoline class (e.g., fluralaner, afoxolaner) (Gassel et al., 2014). These drugs function as non-competitive antagonists, binding to an allosteric site within the channel's transmembrane pore to block chloride flow. This blockage leads to neuronal hyperexcitation, paralysis, and death of the parasite (Weber & Selzer, 2016). The therapeutic utility of targeting RDL stems from its high selectivity; structural differences between the invertebrate RDL receptor and the mammalian GABA-A receptor allow these drugs to be highly toxic to parasites while remaining safe for the host (Ozoe, 2013). Resistance to these agents is frequently associated with specific point mutations in the RDL gene, such as the A301S or A301G substitutions, which reduce drug binding affinity (Ffrench-Constant et al., 2000). Consequently, monitoring these mutations is essential for managing resistance in veterinary and agricultural settings.

Other names

GABA-gated chloride channelResistance to dieldrin proteinGABA receptorIonotropic GABA receptorGABA-Cl

Non-competitive antagonism of the chloride channel pore, leading to hyperexcitation and paralysis of the parasite.