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dc.contributor.author
Perissinotti, Paula Patricia
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dc.contributor.author
Martínez Hernández, Elizabeth
dc.contributor.author
He, Yungui
dc.contributor.author
Koob, Michael D.
dc.contributor.author
Piedras Rentería, Erika S.
dc.date.available
2022-10-28T12:53:37Z
dc.date.issued
2021-09
dc.identifier.citation
Perissinotti, Paula Patricia; Martínez Hernández, Elizabeth; He, Yungui; Koob, Michael D.; Piedras Rentería, Erika S.; Genetic Deletion of KLHL1 Leads to Hyperexcitability in Hypothalamic POMC Neurons and Lack of Electrical Responses to Leptin; Frontiers Media; Frontiers in Neuroscience; 15; 9-2021; 1-16
dc.identifier.issn
1662-453X
dc.identifier.uri
http://hdl.handle.net/11336/175314
dc.description.abstract
Kelch-like 1 (KLHL1) is a neuronal actin-binding protein that modulates voltage-gated calcium channels. The KLHL1 knockout (KO) model displays altered calcium channel expression in various brain regions. We analyzed the electrical behavior of hypothalamic POMC (proopiomelanocortin) neurons and their response to leptin. Leptin’s effects on POMC neurons include enhanced gene expression, activation of the ERK1/2 pathway and increased electrical excitability. The latter is initiated by activation of the Jak2-PI3K-PLC pathway, which activates TRPC1/5 (Transient Receptor Potential Cation) channels that in turn recruit T-type channel activity resulting in increased excitability. Here we report over-expression of CaV3.1 T-type channels in the hypothalamus of KLHL1 KO mice increased T-type current density and enhanced POMC neuron basal excitability, rendering them electrically unresponsive to leptin. Electrical sensitivity to leptin was restored by partial blockade of T-type channels. The overexpression of hypothalamic T-type channels in POMC neurons may partially contribute to the obese and abnormal feeding phenotypes observed in KLHL1 KO mice.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Frontiers Media
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by/2.5/ar/
dc.subject
CAV3.1
dc.subject
KELCH-LIKE 1
dc.subject
LEPTIN
dc.subject
POMC
dc.subject
T-TYPE CALCIUM CHANNELS
dc.subject.classification
Neurociencias
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dc.subject.classification
Medicina Básica
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dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
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dc.title
Genetic Deletion of KLHL1 Leads to Hyperexcitability in Hypothalamic POMC Neurons and Lack of Electrical Responses to Leptin
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2022-09-23T14:24:57Z
dc.journal.volume
15
dc.journal.pagination
1-16
dc.journal.pais
Suiza
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dc.journal.ciudad
Lausanne
dc.description.fil
Fil: Perissinotti, Paula Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
dc.description.fil
Fil: Martínez Hernández, Elizabeth. Loyola University Of Chicago; Estados Unidos
dc.description.fil
Fil: He, Yungui. University of Minnesota; Estados Unidos
dc.description.fil
Fil: Koob, Michael D.. University of Minnesota; Estados Unidos
dc.description.fil
Fil: Piedras Rentería, Erika S.. Loyola University Of Chicago; Estados Unidos
dc.journal.title
Frontiers in Neuroscience
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.3389/fnins.2021.718464
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