Gamma-aminobutyric acid receptor, nematode type (UNC-49, GABA-A receptor, C. elegans) (Nematode GABA-A receptor)

The **nematode GABA-A receptor** is a ligand-gated chloride ion channel found in nematode nervous systems, especially studied in *Caenorhabditis elegans* and various parasitic nematodes[2][7]. It is encoded by the *unc-49* gene, which produces multiple subunits (UNC-49A, UNC-49B, UNC-49C) via alternative splicing[2][3]. The physiologically functional receptor at the neuromuscular junction is primarily a heteromer of UNC-49B and UNC-49C, where UNC-49B serves as the principal GABA-responsive and synaptic localization unit, while UNC-49C modulates desensitization kinetics and shapes inhibitory postsynaptic currents[2][3]. This receptor is central to inhibitory neurotransmission, enabling muscle relaxation during locomotion by conducting chloride ions in response to GABA released from inhibitory neurons[3][7]. It differs from vertebrate GABA-A receptors in its subunit composition and pharmacology, providing opportunities for selective anthelmintic drug development. Several anthelmintics (notably ivermectin) target nematode GABA-A receptors, often leading to paralysis and death of the worm[7][3]. Resistance to such drugs is a major concern in parasitic nematode infections affecting animals and humans.

Other names

UNC-49 receptornematode GABA-A receptorGABA-gated chloride channelUNC-49B/UNC-49C receptor

Positive allosteric modulation (ivermectin enhances channel activity); Antagonism (picrotoxin blocks the chloride channel); Agonism (muscimol acts as a full agonist); Inhibition/desensitization modulation (pregnenolone sulfate acts as an antagonist)[2][3][7]