Distribution of glutamate-gated chloride channel subunits in the parasitic nematode Haemonchus contortus.

Glutamate-gated chloride channels (GluCl) are related to gamma-aminobutyric acid-A (GABA(A)) receptors and are the target sites for the avermectin/milbemycin (A/M) anthelmintics, drugs that cause paralysis of the somatic and pharyngeal muscles in nematodes. We have previously identified four GluCl subunits, HcGluClalpha, HcGluClbeta, HcGluClalpha3A, and HcGluClalpha3B from the sheep parasite Haemonchus contortus. We raised specific antisera against all of these subunits and used them in immunofluorescence experiments on adult parasites. All of the subunits were expressed in the motor nervous system, especially motor neuron commissures. Double-immunostaining experiments suggested that HcGluClalpha and HcGluClbeta were expressed on the same commissures; these were also stained with an anti-GABA antibody, suggesting that they may be inhibitory motor neurons. The HcGluClbeta subunit was also detected in lateral and sublateral nerve cords. The HcGluClalpha3A and -B subunits, products of an alternatively spliced gene, were expressed in different neurons. We found HcGluClalphaA in a pair of sensory, possibly amphid, neurons in the head, in addition to the motor neuron commissures. HcGluClalpha3B was detected in three cell bodies, probably of pharyngeal neurons, and to ventral and lateral cords. These results indicate that the GluCl are widely distributed in the H. contortus nervous system and suggest that they have critical roles controlling locomotion, pharyngeal function, and possibly sensory processing in parasitic nematodes. They also provide an explanation for the observed effects of the A/M anthelmintics.