NaV1.6 regulates excitability of mechanosensitive sensory neurons
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Le résumé fourni par la source
Key points Voltage‐gated sodium channels are critical for peripheral sensory neuron transduction and have been implicated in a number of painful and painless disorders. The β‐scorpion toxin, Cn2, is selective for NaV1.6 in dorsal root ganglion neurons. NaV1.6 plays an essential role in peripheral sensory neurons, specifically at the distal terminals of mechanosensing fibres innervating the skin and colon. NaV1.6 activation also leads to enhanced response to mechanical stimulus in vivo. This works highlights the use of toxins in elucidating pain pathways moreover the importance of non‐peripherally restricted NaV isoforms in pain generation. Abstract Peripheral sensory neurons express multiple voltage‐gated sodium channels (NaV) critical for the initiation and propagation of action potentials and transmission of sensory input. Three pore‐forming sodium channel isoforms are primarily expressed in the peripheral nervous system (PNS): NaV1.7, NaV1.8 and NaV1.9. These sodium channels have been implicated in painful and painless channelopathies and there has been intense interest in them as potential therapeutic targets in human pain. Emerging evidence suggests NaV1.6 channels are an important isoform in pain sensing. This study aimed to assess, using pharmacological approaches, the function of NaV1.6 channels in peripheral sensory neurons. The potent and NaV1.6 selective β‐scorpion toxin Cn2 was used to assess the effect of NaV1.6 channel activation in the PNS. The multidisciplinary approach included Ca2+ imaging, whole‐cell patch‐clamp recordings, skin–nerve and gut–nerve preparations and in vivo behavioural assessment of pain. Cn2 facilitates NaV1.6 early channel opening, and increased persistent and resurgent currents in large‐diameter dorsal root ganglion (DRG) neurons. This promotes enhanced excitatory drive and tonic action potential firing in these neurons. In addition, NaV1.6 channel activation in the skin and gut leads to increased response to mechanical stimuli. Finally, intra‐plantar injection of Cn2 causes mechanical but not thermal allodynia. This study confirms selectivity of Cn2 on NaV1.6 channels in sensory neurons. Activation of NaV1.6 channels, in terminals of the skin and viscera, leads to profound changes in neuronal responses to mechanical stimuli. In conclusion, sensory neurons expressing NaV1.6 are important for the transduction of mechanical information in sensory afferents innervating the skin and viscera.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé, mais le titre doit être comparé manuellement.
- Titre Crossref
- Na<sub>V</sub>1.6 regulates excitability of mechanosensitive sensory neurons
- Date Crossref
- 18/06/2019
- Éditeur
- Wiley
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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The University of Queensland Institute for Molecular Bioscience pays non établi dans la noticeUniversité ou école supérieure
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Yale University pays non établi dans la noticeUniversité ou école supérieure
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VA Connecticut Healthcare System pays non établi dans la noticeÉtablissement de santé
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Center for Neuroscience and Regenerative Medicine pays non établi dans la noticeStructure de recherche
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Flinders University pays non établi dans la noticeUniversité ou école supérieure
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South Australian Health and Medical Research Institute pays non établi dans la noticeÉtablissement de santé
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The University of Adelaide Discipline of Medicine pays non établi dans la noticeUniversité ou école supérieure
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Translational Research Institute pays non établi dans la noticeStructure de recherche
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Institute for Molecular Bioscience IMB Centre for Pain Research pays non établi dans la noticeStructure de recherche
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Center for Neuroscience and Regeneration Research Yale School of Medicine New Haven CT 06510 USA Center for Neuroscience and Regeneration Research pays non établi dans la noticeUniversité ou école supérieure
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Department of Neurology Yale School of Medicine New Haven CT 06510 USA pays non établi dans la noticeUniversité ou école supérieure
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Rehabilitation Research Center pays non établi dans la noticeStructure de recherche
Institute for Molecular Bioscience — The University of Queensland, Yale University et VA Connecticut Healthcare System, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.