Insect glutamate-gated chloride channel (GluCl)

Insect glutamate-gated chloride channels (GluCls) are members of the Cys-loop ligand-gated ion channel superfamily that mediate fast inhibitory neurotransmission in invertebrates. These channels are primarily expressed in the nervous system and muscles of insects and nematodes, where they regulate locomotion, feeding, and sensory input by conducting chloride ions to hyperpolarize cells (Wolstenholme, 2012, PubMed). Because GluCls are not found in mammals, they represent a critical and highly selective target for insecticides and anthelmintics (Cully et al., 1994, Nature). Macrocyclic lactones, such as ivermectin, bind to the transmembrane domain of the channel, acting as allosteric agonists that keep the pore open and cause flaccid paralysis (Hibbs & Gouaux, 2011, Nature). More recently, isoxazoline insecticides have been developed to act as non-competitive antagonists of these channels, leading to lethal hyperexcitation in pests (Weber & Selzer, 2016, Veterinary Medicine and Science). The high selectivity of these drugs for invertebrate GluCls over vertebrate GABA receptors ensures a broad safety margin, though mutations in GluCl subunits can lead to significant drug resistance in the field (Menez et al., 2012, British Journal of Pharmacology).

Other names

Glutamate-gated chloride channelGluClRInvertebrate glutamate-gated chloride channelH-receptorAvermectin-sensitive glutamate-gated chloride channel

Positive allosteric modulation or direct activation leading to persistent chloride influx and membrane hyperpolarization; or non-competitive antagonism blocking inhibitory neurotransmission.