INVESTIGADORES
RAYES Diego Hernan
congresos y reuniones científicas
Título:
The alpha-type subunit LEV-8 governs the desensitization process of C.elegans levamisole-sensitive nicotinic receptors
Autor/es:
HERNANDO GUILLERMINA; RAYES DIEGO; BERGE IGNACIO; BOUZAT CECILIA
Lugar:
Huerta Grande, Córdoba
Reunión:
Congreso; First Joint Meeting of the Argentine Society for Neuroscience (SAN) and the Argentine Workshop in Neurosciences (TAN).; 2009
Institución organizadora:
Sociedad Argentina de Investigación en Neurociencias
Resumen:
C. elegans is a
free-living nematode and 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 alpha-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.
We conclude
that LEV-8 is an accessory subunit that governs the desensitization process of
the L-AChR. This study contributes to the elucidation of the stoichiometry of
functional nematode muscle L-AChRs