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Sensory neuron–derived Na(V)1.7 contributes to dorsal horn neuron excitability
Expression of the voltage-gated sodium channel Na(V)1.7 in sensory neurons is required for pain sensation. We examined the role of Na(V)1.7 in the dorsal horn of the spinal cord using an epitope-tagged Na(V)1.7 knock-in mouse. Immuno–electron microscopy showed the presence of Na(V)1.7 in dendrites o...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7030926/ https://www.ncbi.nlm.nih.gov/pubmed/32128393 http://dx.doi.org/10.1126/sciadv.aax4568 |
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author | Alles, Sascha R. A. Nascimento, Filipe Luján, Rafael Luiz, Ana P. Millet, Queensta Bangash, M. Ali Santana-Varela, Sonia Zhou, Xuelong Cox, James J. Okorokov, Andrei L. Beato, Marco Zhao, Jing Wood, John N. |
author_facet | Alles, Sascha R. A. Nascimento, Filipe Luján, Rafael Luiz, Ana P. Millet, Queensta Bangash, M. Ali Santana-Varela, Sonia Zhou, Xuelong Cox, James J. Okorokov, Andrei L. Beato, Marco Zhao, Jing Wood, John N. |
author_sort | Alles, Sascha R. A. |
collection | PubMed |
description | Expression of the voltage-gated sodium channel Na(V)1.7 in sensory neurons is required for pain sensation. We examined the role of Na(V)1.7 in the dorsal horn of the spinal cord using an epitope-tagged Na(V)1.7 knock-in mouse. Immuno–electron microscopy showed the presence of Na(V)1.7 in dendrites of superficial dorsal horn neurons, despite the absence of mRNA. Rhizotomy of L5 afferent nerves lowered the levels of Na(V)1.7 in the dorsal horn. Peripheral nervous system–specific Na(V)1.7 null mutant mice showed central deficits, with lamina II dorsal horn tonic firing neurons more than halved and single spiking neurons more than doubled. Na(V)1.7 blocker PF05089771 diminished excitability in dorsal horn neurons but had no effect on Na(V)1.7 null mutant mice. These data demonstrate an unsuspected functional role of primary afferent neuron-generated Na(V)1.7 in dorsal horn neurons and an expression pattern that would not be predicted by transcriptomic analysis. |
format | Online Article Text |
id | pubmed-7030926 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-70309262020-03-03 Sensory neuron–derived Na(V)1.7 contributes to dorsal horn neuron excitability Alles, Sascha R. A. Nascimento, Filipe Luján, Rafael Luiz, Ana P. Millet, Queensta Bangash, M. Ali Santana-Varela, Sonia Zhou, Xuelong Cox, James J. Okorokov, Andrei L. Beato, Marco Zhao, Jing Wood, John N. Sci Adv Research Articles Expression of the voltage-gated sodium channel Na(V)1.7 in sensory neurons is required for pain sensation. We examined the role of Na(V)1.7 in the dorsal horn of the spinal cord using an epitope-tagged Na(V)1.7 knock-in mouse. Immuno–electron microscopy showed the presence of Na(V)1.7 in dendrites of superficial dorsal horn neurons, despite the absence of mRNA. Rhizotomy of L5 afferent nerves lowered the levels of Na(V)1.7 in the dorsal horn. Peripheral nervous system–specific Na(V)1.7 null mutant mice showed central deficits, with lamina II dorsal horn tonic firing neurons more than halved and single spiking neurons more than doubled. Na(V)1.7 blocker PF05089771 diminished excitability in dorsal horn neurons but had no effect on Na(V)1.7 null mutant mice. These data demonstrate an unsuspected functional role of primary afferent neuron-generated Na(V)1.7 in dorsal horn neurons and an expression pattern that would not be predicted by transcriptomic analysis. American Association for the Advancement of Science 2020-02-19 /pmc/articles/PMC7030926/ /pubmed/32128393 http://dx.doi.org/10.1126/sciadv.aax4568 Text en Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Alles, Sascha R. A. Nascimento, Filipe Luján, Rafael Luiz, Ana P. Millet, Queensta Bangash, M. Ali Santana-Varela, Sonia Zhou, Xuelong Cox, James J. Okorokov, Andrei L. Beato, Marco Zhao, Jing Wood, John N. Sensory neuron–derived Na(V)1.7 contributes to dorsal horn neuron excitability |
title | Sensory neuron–derived Na(V)1.7 contributes to dorsal horn neuron excitability |
title_full | Sensory neuron–derived Na(V)1.7 contributes to dorsal horn neuron excitability |
title_fullStr | Sensory neuron–derived Na(V)1.7 contributes to dorsal horn neuron excitability |
title_full_unstemmed | Sensory neuron–derived Na(V)1.7 contributes to dorsal horn neuron excitability |
title_short | Sensory neuron–derived Na(V)1.7 contributes to dorsal horn neuron excitability |
title_sort | sensory neuron–derived na(v)1.7 contributes to dorsal horn neuron excitability |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7030926/ https://www.ncbi.nlm.nih.gov/pubmed/32128393 http://dx.doi.org/10.1126/sciadv.aax4568 |
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