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dc.contributor.author
Martínez Hernández, Elizabeth
dc.contributor.author
Zeglin, Alissa
dc.contributor.author
Almazan, Erik
dc.contributor.author
Perissinotti, Paula Patricia
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He, Yungui
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Koob, Michael
dc.contributor.author
Martin, Jody L.
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Piedras-Rentería, Erika S.
dc.date.available
2021-10-06T22:47:16Z
dc.date.issued
2020-01
dc.identifier.citation
Martínez Hernández, Elizabeth; Zeglin, Alissa; Almazan, Erik; Perissinotti, Paula Patricia; He, Yungui; et al.; KLHL1 Controls CaV3.2 Expression in DRG Neurons and Mechanical Sensitivity to Pain; Frontiers Media; Frontiers in Molecular Neuroscience; 12; 315; 1-2020; 1-10
dc.identifier.issn
1662-5099
dc.identifier.uri
http://hdl.handle.net/11336/142996
dc.description.abstract
Dorsal root ganglion (DRG) neurons process pain signaling through specialized nociceptors located in their peripheral endings. It has long been established low voltage-activated (LVA) CaV3.2 calcium channels control neuronal excitability during sensory perception in these neurons. Silencing CaV3.2 activity with antisense RNA or genetic ablation results in anti-nociceptive, anti-hyperalgesic and anti-allodynic effects. CaV3.2 channels are regulated by many proteins (Weiss and Zamponi, 2017), including KLHL1, a neuronal actin-binding protein that stabilizes channel activity by recycling it back to the plasma membrane through the recycling endosome. We explored whether manipulation of KLHL1 levels and thereby function as a CaV3.2 modifier can modulate DRG excitability and mechanical pain transmission or sensitivity to pain. We first assessed the mechanical sensitivity threshold and DRG properties in the KLHL1 KO mouse model. KO DRG neurons exhibited smaller T-type current density compared to WT without significant changes in voltage dependence, as expected in the absence of its modulator. Western blot analysis confirmed CaV3.2 but not CaV3.1, CaV3.3, CaV2.1, or CaV2.2 protein levels were significantly decreased; and reduced neuron excitability and decreased pain sensitivity were also found in the KLHL1 KO model. Analogously, transient down-regulation of KLHL1 levels in WT mice with viral delivery of anti-KLHL1 shRNA also resulted in decreased pain sensitivity. These two experimental approaches confirm KLHL1 as a physiological modulator of excitability and pain sensitivity, providing a novel target to control peripheral pain.
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-nc-sa/2.5/ar/
dc.subject
CAV3.2
dc.subject
DRG
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KLHL1
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MECHANICAL SENSITIVITY
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PAIN CONTROL
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SHRNA
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T-TYPE CHANNEL
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VOLTAGE-GATED CALCIUM CHANNEL
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Neurociencias
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dc.subject.classification
Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
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dc.title
KLHL1 Controls CaV3.2 Expression in DRG Neurons and Mechanical Sensitivity to Pain
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2021-09-07T18:41:59Z
dc.journal.volume
12
dc.journal.number
315
dc.journal.pagination
1-10
dc.journal.pais
Suiza
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dc.description.fil
Fil: Martínez Hernández, Elizabeth. Loyola University Chicago; Estados Unidos
dc.description.fil
Fil: Zeglin, Alissa. Loyola University Chicago; Estados Unidos
dc.description.fil
Fil: Almazan, Erik. Loyola University Chicago; Estados Unidos
dc.description.fil
Fil: Perissinotti, Paula Patricia. Loyola University Chicago; Estados Unidos. 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
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Fil: He, Yungui. University of Minnesota; Estados Unidos
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Fil: Koob, Michael. University of Minnesota; Estados Unidos
dc.description.fil
Fil: Martin, Jody L.. Loyola University Chicago; Estados Unidos
dc.description.fil
Fil: Piedras-Rentería, Erika S.. Loyola University Chicago; Estados Unidos
dc.journal.title
Frontiers in Molecular Neuroscience
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/article/10.3389/fnmol.2019.00315/full
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.3389/fnmol.2019.00315
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