Mostrar el registro sencillo del ítem
dc.contributor.author
Andersen, Natalia Denise
dc.contributor.author
Corradi, Jeremias
dc.contributor.author
Sine, Steven M.
dc.contributor.author
Bouzat, Cecilia Beatriz
dc.date.available
2016-07-05T15:25:20Z
dc.date.issued
2013-12
dc.identifier.citation
Andersen, Natalia Denise; Corradi, Jeremias; Sine, Steven M.; Bouzat, Cecilia Beatriz; Stoichiometry for activation of neuronal alpha7 nicotinic receptors; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 110; 51; 12-2013; 20819-20824
dc.identifier.issn
0027-8424
dc.identifier.uri
http://hdl.handle.net/11336/6360
dc.description.abstract
Neuronal α7 nicotinic receptors elicit rapid cation influx in response to acetylcholine (ACh) or its hydrolysis product choline. They contribute to cognition, synaptic plasticity, and neuroprotection and have been implicated in neurodegenerative and neuropsychiatric disorders. α7, however, often localizes distal to sites of nerve-released ACh and binds ACh with low affinity, and thus elicits its biological response with low agonist occupancy. To assess the function of α7 when ACh occupies fewer than five of its identical binding sites, we measured the open-channel lifetime of individual receptors in which four of the five ACh binding sites were disabled. To improve the time resolution of the inherently brief α7 channel openings, background mutations or a potentiator was used to increase open duration. We find that, in receptors with only one intact binding site, the open-channel lifetime is indistinguishable from receptors with five intact binding sites, counter to expectations from prototypical neurotransmitter-gated ion channels where the open-channel lifetime increases with the number of binding sites occupied by agonist. Replacing the membrane-embedded domain of α7 by that of the related 5-HT3A receptor increases the number of sites that need to be occupied to achieve the maximal open-channel lifetime, thus revealing a unique interdependence between the detector and actuator domains of these receptors. The distinctive ability of a single occupancy to elicit a full biological response adapts α7 to volume transmission, a prevalent mechanism of ACh-mediated signaling in the nervous system and nonneuronal cells.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
National Academy of Sciences
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Cys Loop Receptors
dc.subject
Alpha7 Nicotinic Receptor
dc.subject
Patch Clamp
dc.subject
Agonist Binding Site
dc.subject
Channel Gating
dc.subject.classification
Bioquímica y Biología Molecular
dc.subject.classification
Ciencias Biológicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.subject.classification
Neurociencias
dc.subject.classification
Medicina Básica
dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Stoichiometry for activation of neuronal alpha7 nicotinic receptors
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2016-05-10T14:32:02Z
dc.journal.volume
110
dc.journal.number
51
dc.journal.pagination
20819-20824
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Washington
dc.description.fil
Fil: Andersen, Natalia Denise. Consejo Nacional de Investigaciones Cientificas y Técnicas. Centro Científico Tecnologico Bahia Blanca. Instituto de Investigaciones Bioquimicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; Argentina
dc.description.fil
Fil: Corradi, Jeremias. Consejo Nacional de Investigaciones Cientificas y Técnicas. Centro Científico Tecnológico Bahia Blanca. Instituto de Investigaciones Bioquímicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; Argentina
dc.description.fil
Fil: Sine, Steven M.. Mayo Clinic College of Medicine; Estados Unidos
dc.description.fil
Fil: Bouzat, Cecilia Beatriz. Consejo Nacional de Investigaciones Cientificas y Técnicas. Centro Científico Tecnológico Bahia Blanca. Instituto de Investigaciones Bioquímicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; Argentina
dc.journal.title
Proceedings of the National Academy of Sciences of The United States of America
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1073/pnas.1315775110
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.pnas.org/content/110/51/20819.long
Archivos asociados