The alpha-type subunit LEV-8 governs the desensitization process of C. elegans Levamvisole-sensitive Nicotinic receptors

HERNANDO, G.; RAYES, D.; BERGE, I.; BOUZAT, C.

Huerta Grande, Cordoba

Congreso; First Join Meeting of the Argentine Society for Neurosciences and the Argentine Workshop in Neurosciences (TAN); 2009

Argentine Society for Neurosciences

C. elegans is a free-living nematode and a representative member of a large phylum thatincludes many parasitic members. Nematode nicotinic acetylcholine receptors (nAChRs)are pentameric ligand-gated ion channels that mediate synaptic transmission throughoutthe nervous system. The muscle levamisole-sensitive nAChR (L-AChR) is the target ofanthelmintic drugs, such as levamisole, which act as potent agonists. Although severalsubunits have been reported to form the L-AChR, its subunit composition and the role ofeach subunit remain unknown. LEV-8 is a a-type subunit of the L-AChR that whenmutated confers partial resistance to the levamisole paralytic effects. To explore thefunctional role of LEV-8, we performed cell-attached and whole-cell recordings ofembryonic muscle cells from wild-type and mutant strains. Recordings from the null mutantstrain lev-8(x-15) show ACh- and levamisole-activated channels with a conductance of39.6±4pS. The kinetics of the channels differs from that of wild-type strains. The meanopen times for ACh- and levamisole-activated channels are 3.9- and 1.5-fold moreprolonged, respectively, than those from wild-type strains. The frequency of channelopenings is markedly reduced with respect to that of wild-type strains. Moreover, in theLEV-8 null mutant strain the frequency decreases significantly with the time of recording,suggesting enhanced desensitization. Macroscopic currents reveal 1.5-fold increase of thedesensitization rate and decreased recovery rate from desensitized states in the LEV-8null mutant strain when compared to the wild type.We conclude that LEV-8 is an accessory subunit that governs the desensitization processof the L-AChR. This study contributes to the elucidation of the stoichiometry of functionalnematode muscle L-AChRs.