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dc.contributor.author
Natarajan, Kathiresan
dc.contributor.author
Mukhtasimova, Nuriya
dc.contributor.author
Corradi, Jeremias
dc.contributor.author
Lasala, Matías Marcelo
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Bouzat, Cecilia Beatriz
dc.contributor.author
Sine, Steven M.
dc.date.available
2020-08-10T19:35:58Z
dc.date.issued
2020-07-23
dc.identifier.citation
Natarajan, Kathiresan; Mukhtasimova, Nuriya; Corradi, Jeremias; Lasala, Matías Marcelo; Bouzat, Cecilia Beatriz; et al.; Mechanism of calcium potentiation of the α7 nicotinic acetylcholine receptor; Rockefeller University Press; Journal Of General Physiology; 152; 9; 23-7-2020; 1-23
dc.identifier.issn
0022-1295
dc.identifier.uri
http://hdl.handle.net/11336/111352
dc.description.abstract
The α7 nicotinic acetylcholine receptor (nAChR) is among the most abundant types of nAChR in the brain, yet the ability of nerve-released ACh to activate α7 remains enigmatic. In particular, a major population of α7 resides in extra-synaptic regions where the ACh concentration is reduced, owing to dilution and enzymatic hydrolysis, yet ACh shows low potency in activating α7. Using high-resolution single-channel recording techniques, we show that extracellular calcium is a powerful potentiator of α7 activated by low concentrations of ACh. Potentiation manifests as robust increases in the frequency of channel opening and the average duration of the openings. Molecular dynamics simulations reveal that calcium binds to the periphery of the five ligand binding sites and is framed by a pair of anionic residues from the principal and complementary faces of each site. Mutation of residues identified by simulation prevents calcium from potentiating ACh-elicited channel opening. An anionic residue is conserved at each of the identified positions in all vertebrate species of α7. Thus, calcium associates with a novel structural motif on α7 and is an obligate cofactor in regions of limited ACh concentration.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Rockefeller University Press
dc.rights
info:eu-repo/semantics/embargoedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
PATCH-CLAMP
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MODULATION
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NICOTINIC
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Biofísica
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Mechanism of calcium potentiation of the α7 nicotinic acetylcholine receptor
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2020-08-04T19:11:34Z
dc.identifier.eissn
1540-7748
dc.journal.volume
152
dc.journal.number
9
dc.journal.pagination
1-23
dc.journal.pais
Estados Unidos
dc.journal.ciudad
New York
dc.description.fil
Fil: Natarajan, Kathiresan. Mayo Clinic Cancer Center; Estados Unidos
dc.description.fil
Fil: Mukhtasimova, Nuriya. Mayo Clinic Cancer Center; Estados Unidos
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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
dc.description.fil
Fil: Lasala, Matías Marcelo. 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
dc.description.fil
Fil: Sine, Steven M.. Mayo Clinic Cancer Center; Estados Unidos
dc.journal.title
Journal Of General Physiology
dc.rights.embargoDate
2021-01-23
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://rupress.org/jgp/article/152/9/e202012606/151971/Mechanism-of-calcium-potentiation-of-the-7
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1085/jgp.202012606
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