Invertebrate glutamate-gated chloride channel (GluCl) (GluCl)

Invertebrate glutamate-gated chloride channels (GluCls) are members of the Cys-loop family of ligand-gated ion channels that mediate fast inhibitory neurotransmission in protostome invertebrates, such as nematodes and arthropods (Wolstenholme, 2012). These channels are activated by the neurotransmitter L-glutamate, leading to an influx of chloride ions that hyperpolarizes the cell membrane and inhibits electrical activity (Hibbs & Gouaux, 2011). A defining feature of GluCls is their absence in vertebrate genomes, which makes them an ideal target for highly selective antiparasitic and insecticidal agents (Cully et al., 1994). The most prominent drugs targeting these channels are the macrocyclic lactones, including ivermectin, which act as potent positive allosteric modulators that stabilize the open state of the channel (Lynagh & Lynch, 2012). This action results in the flaccid paralysis of the parasite's somatic muscles and pharynx, preventing movement and feeding, and eventually leading to the death of the organism (Wolstenholme, 2012). In clinical practice, these channels are central to the treatment of human diseases like onchocerciasis and various veterinary parasitic infections, though their utility is increasingly threatened by the emergence of drug resistance (Menez et al., 2012).

Other names

Glutamate-gated chloride channelGluCl receptorAvermectin-sensitive glutamate-gated chloride channelGluClRH-receptor

Positive allosteric modulation and agonism of the channel, leading to increased chloride ion permeability, hyperpolarization of neurons and muscle cells, and subsequent flaccid paralysis (Wolstenholme, 2012).