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AgGluCl-β (Anopheles gambiae glutamate-gated chloride channel beta subunit) is a critical component of the inhibitory neurotransmission system in the malaria-carrying mosquito (UniProt Q7PYH5). As a member of the Cys-loop ligand-gated ion channel (LGIC) superfamily, it forms chloride-selective pores that are activated by the neurotransmitter glutamate (PMID: 17610318). These channels are unique to invertebrates and are absent in mammals, which makes them highly attractive targets for selective insecticides and endectocides (PMID: 25104775). The beta subunit often co-assembles with alpha subunits to form heteromeric channels that mediate fast inhibitory postsynaptic potentials. Drugs such as ivermectin and other macrocyclic lactones act as potent positive allosteric modulators of these channels, binding to the transmembrane domains and causing persistent channel opening (PMID: 20566640). This leads to a continuous influx of chloride ions, resulting in membrane hyperpolarization, muscle paralysis, and the eventual death of the mosquito vector (PMID: 21931557).
Positive allosteric modulation and activation of the chloride channel, leading to membrane hyperpolarization and flaccid paralysis of the insect.
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