Invertebrate glutamate-gated chloride channel receptor (GluCl)

The invertebrate glutamate-gated chloride channel receptor (GluCl) is a member of the Cys-loop family of ligand-gated ion channels, found exclusively in protostome invertebrates such as nematodes and arthropods (Wolstenholme, 2012, PubMed: 22512310). These receptors mediate fast inhibitory neurotransmission by facilitating the influx of chloride ions into neurons and muscle cells upon binding the neurotransmitter L-glutamate, resulting in membrane hyperpolarization (Cully et al., 1994, Nature: 371(6499)). GluCls play vital roles in regulating locomotion, feeding, and sensory input in parasites. They are the primary molecular targets for the macrocyclic lactone class of antiparasitic drugs, including ivermectin and moxidectin (Hibbs & Gouaux, 2011, Nature: 474(7349)). These drugs act as potent allosteric agonists, locking the channel in an open state, which leads to flaccid paralysis and the eventual death or expulsion of the parasite from the host. Because GluCls are absent in vertebrate genomes, these drugs typically exhibit a high margin of safety for the host. However, neurotoxicity can occur in hosts with compromised blood-brain barriers or specific genetic mutations in efflux transporters like MDR1 (Mealey et al., 2001, Pharmacogenetics: 11(8)).

Other names

Glutamate-gated chloride channelGluClRAvermectin-sensitive glutamate-gated chloride channel

Positive allosteric modulation and activation of the channel, leading to increased chloride conductance, membrane hyperpolarization, and flaccid paralysis of the parasite (Hibbs & Gouaux, 2011, Nature).