Characterization of a Choline-Gated Chloride Channel (LGC-40) from Haemonchus contortus Highlights a Novel Cholinergic Binding Site

Nematode cys-loop ligand-gated chloride channels are important targets for anthelmintic drugs as many subtypes are not present in mammals. We report the isolation and functional characterization of a novel member of the cys-loop ligand-gated chloride channel family (Hco-LGC-40) from the parasitic nematode Haemonchus contortus. Electrophysiological analysis of the channel expressed in Xenopus oocytes revealed that it responds to both acetylcholine and choline with EC50 values in the low micromolar range. Hco-LGC-40 can also associate with a member of a separate family of acetylcholine-gated chloride channels, Hco-ACC-1, to produce a heteromeric channel with a lower sensitivity to acetylcholine. In silico analysis reveals several residues that may play a role in forming a unique cholinergic binding pocket. Overall, these results suggest that choline may act as a neurotransmitter by binding to cys-loop receptors in parasitic nematodes.