Glutamate-gated chloride channel protein (GluCl or GluClR)

The glutamate-gated chloride channel protein (GluCl or GluClR) is a pentameric ligand-gated ion channel belonging to the Cys-loop receptor superfamily, unique to invertebrates. Its activation by extracellular glutamate allows chloride ions to flow across the cell membrane, resulting in fast inhibitory synaptic transmission. The channel plays a critical role in controlling locomotion, feeding, and other behaviors in nematodes and arthropods[3][5][6][7]. GluCl is the primary molecular target for ivermectin and other broad-spectrum anthelmintics: these drugs bind allosterically, locking the channel in an open conformation, which leads to sustained hyperpolarization, paralysis, and death of the parasite[4][5][6]. Due to its absence in mammals, GluCl represents an ideal molecular target for selective antiparasitic therapies. However, widespread use of avermectins has led to an increase in resistant parasite populations, driven by mutations in GluCl subunit genes[4][7]. GluCl has no known major roles in human physiology or disease but is of significant importance for drug discovery in agriculture and tropical medicine[6][7].

Other names

GluClGlutamate-gated chloride channel receptorGlutamate-gated chloride channel subunit (e.g., glc-1, glc-2, species/isoform specific)Glutamate-gated chloride ion channel

Direct agonism (ivermectin/avermectins: irreversibly open channel, causing sustained chloride influx and hyperpolarization leading to paralysis of invertebrates); Competitive inhibition/blockade (picrotoxin, flufenamic acid: block channel function); Agonist/activation (glutamate: physiological activator; ibotenate: research agonist)