GABA-gated chloride channel receptor (RDL)

The insect/acarine GABA-gated chloride channel receptor, primarily represented by the RDL (Resistance to dieldrin) subunit, is a pentameric ligand-gated ion channel that mediates fast inhibitory neurotransmission in the arthropod nervous system. Upon binding the neurotransmitter gamma-aminobutyric acid (GABA), the receptor undergoes a conformational change that opens a central pore, allowing chloride ions to flow into the neuron and hyperpolarize the membrane. This receptor is a critical target for several major classes of insecticides and acaricides, including phenylpyrazoles (e.g., fipronil), cyclodienes (e.g., dieldrin), and isoxazolines (e.g., fluralaner). These compounds typically act as non-competitive antagonists by binding to a site within the channel pore, thereby blocking the inhibitory effect of GABA and leading to lethal neuronal hyperexcitation and paralysis. While it shares structural similarities with vertebrate GABA-A receptors, the insect/acarine receptor possesses unique pharmacological characteristics that enable the development of highly selective pest control agents with low mammalian toxicity. However, the widespread use of these chemicals has led to the emergence of target-site resistance, most commonly through specific mutations like A301S or A302S in the M2 transmembrane domain, which reduce drug binding affinity.

Other names

Resistance to dieldrin proteinRDL receptorGABA-gated chloride channel (GABACl)Insect GABA receptorAcarine GABA receptorIonotropic GABA receptor

Non-competitive antagonism of the chloride channel pore; Allosteric inhibition of GABA-induced currents