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Gamma-aminobutyric acid-gated chloride channels (GABA-gated Cl⁻ channels) are ligand-gated ion channels that open in response to the binding of gamma-aminobutyric acid (GABA), allowing chloride ions to flow across cell membranes. In parasitic organisms, these channels play a crucial role in regulating neuronal excitability and muscle function, often differing structurally and pharmacologically from their mammalian counterparts. These receptors mediate inhibitory neurotransmission by increasing membrane permeability to Cl⁻ ions upon GABA binding, leading to hyperpolarization of neurons and reduced neuronal firing. Disruption or modulation of these channels can result in paralysis or altered behavior in the parasite. These receptors are major targets for anthelmintic drugs such as avermectins (e.g., ivermectin) which bind allosterically causing persistent opening of the channel, resulting in flaccid paralysis and death of the parasite. The structural differences between parasite-specific GABA-Cl⁻ receptors and those found in mammals allow selective targeting by drugs with minimal host toxicity.
Allosteric binding leading to persistent channel opening and uncontrolled Cl⁻ influx
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