Glutamate-gated chloride channel (parasitic) (GluCl)

Glutamate-gated chloride channels are pentameric ligand-gated ion channels present in protostome invertebrates such as nematodes, arthropods, mollusks, and some parasitic species. They belong to the Cys-loop receptor superfamily and function as inhibitory channels; when activated by glutamate, they permit chloride ions to flow into cells, producing hyperpolarization, which dampens neuronal excitability. These channels are crucial for locomotor and sensory functions and are the molecular targets of widely used antiparasitic and pesticidal drugs in the macrocyclic lactone family, including ivermectin, abamectin, doramectin, eprinomectin, selamectin, moxidectin, and emamectin. Drug binding to GluCl induces sustained activation, leading to parasite paralysis and death. Emergence of resistance due to mutations in GluCl subunits is a significant challenge in clinical and agricultural applications. The specificity of GluCl for invertebrates underlies its value as a selective antiparasitic target, with minimal risk for direct effects in vertebrates.

Other names

GluClglutamate-gated chloride channel receptorligand-gated chloride channel (glutamate subtype)Cys-loop ligand-gated ion channel (GluCl subclass)

Agonist/irreversible activator: Drugs such as ivermectin and abamectin bind and activate GluCl irreversibly, causing sustained chloride influx and neuronal/muscle hyperpolarization (paralysis and death of parasite) Potentiation of endogenous glutamate-induced channel opening (increasing channel permeability and effect)