Nicotinic receptors at the neuromuscular endplate of Caenorhabditis elegans

FLAMINI, M.; D. RAYES,; HERNANDO, G.; CECILIA BEATRIZ BOUZAT

Pinamar

Congreso; Panamerican Association for Biochemistry and Molecular Biology (PABMB) SAIB/SAN; 2005

Nicotinic acetylcholine receptors (AChRs) are pentameric ligand-gated ion channels that mediate synaptic transmission in both vertebrates and invertebrates. Nematode AChRs are of interest because they are targets for anthelmintic drugs as levamisole. The adult C.elegans neuromuscular junction contains at least two distinct nAChRs: the levamisole-sensitive receptor (LSR), and the levamisole-insensitive receptor. The subunit composition and activation kinetics of these AChRs remain unknown. By setting up a primary culture method that allows differentiation of C. elegans embryonic cells larva 1 (L1) muscle cells in vitro we described for the first time single-channel currents from AChRs of this nematode. Our results show that channels can be activated by both ACh and levamisole. Amplitude histograms of AChRs activated by ACh or levamisole at a membrane potential of ?100 mV can be fitted by a main component of about 3.7 pA. The mean open time values are very similar for ACh- and levamisole-activated channels. These results suggest that a single AChR population is present at the L1 stage. Furthermore, single-channel recordings from levamisole-resistant mutants lacking the UNC-38 subunit, which has been shown to form the LSR, are similar to those obtained from wild-type nematodes. Our observations suggest that nematode AChRs have different developmental expression patterns and provide new insights into the relationship between antiparasitic drug sensitivity and developmental stage.