CONICET | Buscador de Institutos y Recursos Humanos

The free-living nematode C. elegans, is a representative member of a large phylum that includes many parasitic members. Nematode nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels that mediate synaptic transmission throughout the nervous system. The muscle levamisole-sensitive nAChR (L-AChR) is the target of anthelmintic drugs, such as levamisole, which act as potent agonists. Although several subunits have been reported to form the L-AChR, its subunit composition and the role of each subunit remain unknown. LEV-8 is a a-type subunit of the L-AChR that when mutated confers partial resistance to the levamisole paralytic effects. To explore the functional role of LEV-8, we performed cell-attached and whole-cell recordings of embryonic muscle cells from wild-type and mutant strains. Recordings from the null mutant strain lev-8(x-15) show ACh- and levamisole-activated channels with a conductance of 39.6±4pS. The kinetics of the channels differs from that of wild-type strains. The mean open times for ACh- and levamisole-activated channels are 3.9- and 1.5-fold more prolonged, respectively, than those from wild-type strains. The frequency of channel openings is markedly reduced with respect to that of wild-type strains. Moreover, in the LEV-8 null mutant strain the frequency decreases significantly with the time of recording, suggesting enhanced desensitization. Macroscopic currents reveal 1.5-fold increase of the desensitization rate and decreased recovery rate from desensitized states in the LEV-8 null mutant strain when compared to the wild type.