1. Neuroscience
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Altered potassium channel distribution and composition in myelinated axons suppresses hyperexcitability following injury

  1. Margarita Calvo  Is a corresponding author
  2. Natalie Richards
  3. Annina B Schmid
  4. Alejandro Barroso
  5. Lan Zhu
  6. Dinka Ivulic
  7. Ning Zhu
  8. Philipp Anwandter
  9. Manzoor A Bhat
  10. Felipe A Court
  11. Stephen B McMahon
  12. David LH Bennett
  1. Wolfson CARD, United Kingdom
  2. King's College London, United Kingdom
  3. Oxford University, United Kingdom
  4. Kings College London, United Kingdom
  5. Facultad de Ciencias Biologicas- Pontificia Universidad Catolica de Chile, Chile
  6. Facultad de Medicina, - Pontificia Universidad Catolica de Chile, Chile
  7. UT Health Science Center at San Antonio, United States
  8. Pontificia Universidad Catolica de Chile, Chile
  9. university of oxford, United Kingdom
Research Article
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Cite this article as: eLife 2016;5:e12661 doi: 10.7554/eLife.12661

Abstract

Neuropathic pain following peripheral nerve injury is associated with hyperexcitability in damaged myelinated sensory axons, which begins to normalise over time. We investigated the composition and distribution of shaker-type-potassium channels (Kv1 channels) within the nodal complex of myelinated axons following injury. At the neuroma that forms after damage, expression of Kv1.1 and 1.2 (normally localised to the juxtaparanode) was markedly decreased. In contrast Kv1.4 and 1.6, which were hardly detectable in the naïve state, showed increased expression within juxtaparanodes and paranodes following injury, both in rats and humans. Within the dorsal root (a site remote from injury) we noted a redistribution of Kv1-channels towards the paranode. Blockade of Kv1 channels with αDTX after injury reinstated hyperexcitability of A-fibre axons and enhanced mechanosensitivity. Changes in the molecular composition and distribution of axonal Kv1 channels, therefore represents a protective mechanism to suppress the hyperexcitability of myelinated sensory axons that follows nerve injury.

Article and author information

Author details

  1. Margarita Calvo

    Kings College London, Wolfson CARD, London, United Kingdom
    For correspondence
    mcalvob@uc.cl
    Competing interests
    The authors declare that no competing interests exist.
  2. Natalie Richards

    Wolfson CARD, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Annina B Schmid

    Nuffield department of clinical neurosciences, Oxford University, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Alejandro Barroso

    Wolfson CARD, Kings College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Lan Zhu

    Wolfson CARD, Kings College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Dinka Ivulic

    Departamento de Fisiologia, Facultad de Ciencias Biologicas- Pontificia Universidad Catolica de Chile, Santiago, Chile
    Competing interests
    The authors declare that no competing interests exist.
  7. Ning Zhu

    Nuffield Department of Clinical Neurosciences, Oxford University, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Philipp Anwandter

    Departamento Ortopedia y Traumatologia, Facultad de Medicina, - Pontificia Universidad Catolica de Chile, Santiago, Chile
    Competing interests
    The authors declare that no competing interests exist.
  9. Manzoor A Bhat

    Department of Physiology, School of Medicine, UT Health Science Center at San Antonio, San Antonio, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Felipe A Court

    Millenium Nucleus for Regenerative Biology, Faculty of Biology, Pontificia Universidad Catolica de Chile, Santiago, Chile
    Competing interests
    The authors declare that no competing interests exist.
  11. Stephen B McMahon

    Wolfson CARD, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  12. David LH Bennett

    Nuffield department of clinical neuroscience, university of oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: This study was performed in strict accordance with UK Home Office and Pontificia Universidad Catolica's regulations.Experimental protocols were reviewed and approved by "Coordinación de Ética, Bioética y Seguridad de las investigaciones UC" (experiments done in Chile- Protocol CBB230/2013) and were performed in accordance to the UK Home Office regulations (experiments done in the UK). We report this study in compliance with the ARRIVE guidelines (20 points checklist).

Human subjects: Informed consent, and consent to publish, was obtained from all subjects to collect and analyze nerve samples before surgery. Subjects underwent surgery by indication of their physician and samples were obtained from biological tissue that was otherwise due to be incinerated.The study protocol was assessed and approved by the Ethics Scientific Committee of the School of Medicine Pontificia Universidad Catolica de Chile (reference number 14-389)

Reviewing Editor

  1. Peggy Mason, University of Chicago, United States

Publication history

  1. Received: October 30, 2015
  2. Accepted: March 15, 2016
  3. Accepted Manuscript published: April 1, 2016 (version 1)
  4. Version of Record published: April 19, 2016 (version 2)

Copyright

© 2016, Calvo et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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