avr-14 encodes two subunits of the glutamate-gated chloride channels (GluCls) that are the targets for the important anthelmintic, ivermectin. The gene, the pattern of alternative splicing that results in the production of the two subunits, and the expression patterns are all highly conserved between C. elegans and the closely related parasitic nematode, Haemonchus contortus . Intracellular recordings from dissected pharynxes showed that
avr-14 mutants retained a wild-type response to applied ivermectin. However, the response to L-glutamate was slightly, but significantly reduced (2-fold lower affinity; n=8), suggesting that there may be a role for AVR-14 in the pharyngeal nervous system. Consistent with this, antibody staining of the dissected pharynxes showed that AVR-14 was expressed on a subset of pharyngeal neurones, probably M1 and M4. Since this antibody did not differentiate between the two splice isoforms, we raised specific antisera against the intracellular loops of the AVR-14A and -14B subunits. In H. contortus , the anti AVR-14A antiserum reacted with a few motor neurone commisures and with a pair of sensory neurones in the head. As observed previously, there was no evidence of synaptic localisation of the receptor, which was detected throughout the cell, including the cell bodies. The anti AVR-14B antiserum reacted with three cell bodies, possibly of pharyngeal neurones, in the head region. These antibodies are currently being used on the C. elegans preparation. Our data suggest a role for AVR-14-containing GluCls in the regulation of pharyngeal pumping and chemosensation in both species, in addition to their previously identified role in locomotion. Currently, we are attempting to rescue the
avr-14 phenotype by expression of the H. contortus subunits.