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dc.contributor.author
Bouzat, Cecilia Beatriz
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Bartos, Mariana
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Corradi, Jeremias
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Sine, Steven M.
dc.date.available
2018-04-26T19:17:40Z
dc.date.issued
2008-07
dc.identifier.citation
Bouzat, Cecilia Beatriz; Bartos, Mariana; Corradi, Jeremias; Sine, Steven M.; The Interface between Extracellular and Transmembrane Domains of Homomeric Cys-Loop Receptors Governs Open-Channel Lifetime and Rate of Desensitization; Society for Neuroscience; Journal of Neuroscience; 28; 31; 7-2008; 7808-7819
dc.identifier.issn
0270-6474
dc.identifier.uri
http://hdl.handle.net/11336/43580
dc.description.abstract
The lifetimes of activated postsynaptic receptor channels contribute to the efficiency of synaptic transmission. Here we show that structural differences within the interface dividing extracellular and transmembrane domains of homomeric 7 and 5-HT3A receptors account for the large differences in open-channel lifetime and time of desensitization onset between these contrasting members of the Cys-loop receptor superfamily. For 7 receptors, agonist-evoked single-channel currents appear mainly as isolated brief openings (o 0.35 ms), whereas macroscopic currents after a step pulse of agonist desensitize rapidly (d 0.4 ms). In contrast for 5-HT3A receptors, agonist-evoked single-channel currents appear as clusters of many long openings in quick succession (cluster 1.2 s), whereas macroscopic currents desensitize slowly (d 1.1 s). A chimeric 7-5HT3A receptor exhibits functional properties intermediate between those of the parent receptors, but the functional signatures of each parent are reconstituted after substituting the major loops within the interface of the extracellular and transmembrane domains from the corresponding parent receptor. Furthermore, these structural loops contribute to open-channel lifetime and time of desensitization onset in a nonadditive manner. The results suggest that desensitization is the major determinant of the lifetimes of activated 7 and 5-HT3A receptors and that functional differences between the two receptors arise primarily through structural differences at the interface between extracellular and transmembrane domains.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Society for Neuroscience
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Acetylcholine
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Chimeric
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Receptors
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Desensitization
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Otras Ciencias Biológicas
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
The Interface between Extracellular and Transmembrane Domains of Homomeric Cys-Loop Receptors Governs Open-Channel Lifetime and Rate of Desensitization
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-04-16T13:37:02Z
dc.journal.volume
28
dc.journal.number
31
dc.journal.pagination
7808-7819
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Baltimore
dc.description.fil
Fil: Bouzat, Cecilia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
dc.description.fil
Fil: Bartos, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
dc.description.fil
Fil: Corradi, Jeremias. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
dc.description.fil
Fil: Sine, Steven M.. Mayo Clinic College of Medicine; Estados Unidos
dc.journal.title
Journal of Neuroscience
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1523/JNEUROSCI.0448-08.2008
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.jneurosci.org/content/28/31/7808
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3844810/
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