The glutamate-gated chloride channels (GluCl) are important in human and veterinary medicine as the sites of action of the avermectin/milbemycin group of anthelmintics and insecticides, the best known of which is ivermectin. Ivermectin causes paralysis of worms, suggesting that the GluCl are likely to play a role in locomotion. In C. elegans, five genes (
avr-14 &-15 and
glc-1, -2 & -3) encode GluCl subunits and at least some of these are widely expressed in the nervous system. We have raised antibodies against the products of all of these genes and are using these to study the distribution of the subunits. So far, we have confirmed that AVR-14B is present in neurones of the motor nervous system. We examined the movement of
avr-14 and
avr-15 mutants and observed a 50% reduction in the duration of forward movement compared to wild type worms. The
avr-14/avr-15 double mutant had an increased reduction compared to either of the single mutants. RNA interference experiments with
avr-14 or
avr-15 on wild-type worms also reduced the duration of forward movements to a similar extent, confirming that we can use this method to study the effect of reducing expression of genes for which no mutant alleles are yet available. In contrast RNAi with glc- 2, which we have reported to be only expressed in pharyngeal muscle, had no effect on locomotion (Table 1). These effects on the duration of forward movements are the opposite to those obtained with mutants in genes encoding the excitatory glutamate receptors, such as NMR-1, that are expressed on the command interneurones. This raises the possibility that the excitatory and inhibitory glutamate receptors act in an antagonistic fashion to regulate locomotion and we are currently trying to determine if
nmr-1 and the GluCl genes are expressed on any of the same neurones.