Mostrar el registro sencillo del ítem
dc.contributor.author
Hernando, Guillermina Silvana

dc.contributor.author
Bouzat, Cecilia Beatriz

dc.date.available
2016-02-29T17:49:23Z
dc.date.issued
2014-04
dc.identifier.citation
Hernando, Guillermina Silvana; Bouzat, Cecilia Beatriz; Caenorhabditis elegans neuromuscular junction: GABA receptors and ivermectin action; Public Library Of Science; Plos One; 9; 4; 4-2014; e95072
dc.identifier.issn
1932-6203
dc.identifier.uri
http://hdl.handle.net/11336/4518
dc.description.abstract
The prevalence of human and animal helminth infections remains staggeringly high, thus urging the need for concerted efforts towards this area of research. GABA receptors, encoded by the unc-49 gene, mediate body muscle inhibition in Caenorhabditis elegans and parasitic nematodes and are targets of anthelmintic drugs. Thus, the characterization of nematode GABA receptors provides a foundation for rational anti-parasitic drug design. We therefore explored UNC-49 channels from C. elegans muscle cultured cells of the first larval stage at the electrophysiological and behavioral levels. Whole-cell recordings reveal that GABA, muscimol and the anthelmintic piperazine elicit macroscopic currents from UNC-49 receptors that decay in their sustained presence, indicating full desensitization. Single-channel recordings show that all drugs elicit openings of ,2.5 pA (+100 mV), which appear either as brief isolated events or in short bursts. The comparison of the lowest concentration required for detectable channel opening, the frequency of openings and the amplitude of macroscopic currents suggest that piperazine is the least efficacious of the three drugs. Macroscopic and single-channel GABA-activated currents are profoundly and apparently irreversibly inhibited by ivermectin. To gain further insight into ivermectin action at C. elegans muscle, we analyzed its effect on single-channel activity of the levamisol-sensitive nicotinic receptor (L-AChR), the excitatory receptor involved in neuromuscular transmission. Ivermectin produces a profound inhibition of the frequency of channel opening without significant changes in channel properties. By revealing that ivermectin inhibits C. elegans muscle GABA and L-AChR receptors, our study adds two receptors to the already known ivermectin targets, thus contributing to the elucidation of its pleiotropic effects. Behavioral assays in worms show that ivermectin potentiates piperazine-induced paralysis, thus suggesting that their combination is a good strategy to overcome the increasing resistance of parasites, an issue of global concern for human and animal health
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Public Library Of Science

dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.subject
Gaba
dc.subject
Caenorhabditis Elegans
dc.subject
Ivermectin
dc.subject
L-Achr
dc.subject.classification
Bioquímica y Biología Molecular

dc.subject.classification
Ciencias Biológicas

dc.subject.classification
CIENCIAS NATURALES Y EXACTAS

dc.title
Caenorhabditis elegans neuromuscular junction: GABA receptors and ivermectin action
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2016-03-30 10:35:44.97925-03
dc.journal.volume
9
dc.journal.number
4
dc.journal.pagination
e95072
dc.journal.pais
Estados Unidos

dc.journal.ciudad
San Francisco
dc.description.fil
Fil: Hernando, Guillermina Silvana. Universidad Nacional del Sur; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina
dc.description.fil
Fil: Bouzat, Cecilia Beatriz. Universidad Nacional del Sur; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina
dc.journal.title
Plos One

dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0095072
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1371/journal.pone.0095072
Archivos asociados