Glutamate-gated chloride channel subunit alpha-3B (GluClα3B)

Dirofilaria immitis GluClα3B is a specific subunit of the glutamate-gated chloride channel (GluCl) found in the heartworm, a parasitic nematode. These channels are members of the Cys-loop family of ligand-gated ion channels and are unique to invertebrates, making them ideal targets for anthelmintic therapy. In the parasite, GluCls mediate inhibitory neurotransmission; when activated by the neurotransmitter glutamate, they allow chloride ions to flow into the cell, causing hyperpolarization and inhibiting electrical activity. This process is critical for the parasite's locomotion, feeding, and reproduction. This receptor is the primary molecular target for macrocyclic lactones, such as ivermectin and moxidectin, which are the gold standard for heartworm prevention. These drugs act as potent allosteric agonists, locking the channel in an open state, which leads to the flaccid paralysis and eventual death of the microfilariae and larvae. Understanding the structure and function of the alpha-3B subunit is particularly important for addressing the growing challenge of macrocyclic lactone resistance observed in certain heartworm strains, as mutations in these channel subunits can reduce drug binding affinity or channel sensitivity.

Other names

Dim-GLC-3BDirofilaria immitis GLC-3BGlutamate-gated chloride channel alpha 3B subunitGluCl alpha 3B

Positive allosteric modulation and activation of the channel, leading to an influx of chloride ions, membrane hyperpolarization, and flaccid paralysis of the parasite's somatic muscles or pharynx.