Altered potassium channel distribution and composition in myelinated axons suppresses hyperexcitability following injury
- Wolfson CARD, United Kingdom
- King's College London, United Kingdom
- Oxford University, United Kingdom
- Kings College London, United Kingdom
- Facultad de Ciencias Biologicas- Pontificia Universidad Catolica de Chile, Chile
- Facultad de Medicina, - Pontificia Universidad Catolica de Chile, Chile
- UT Health Science Center at San Antonio, United States
- Pontificia Universidad Catolica de Chile, Chile
- university of oxford, United Kingdom
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.
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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)
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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Altered potassium channel distribution and composition in myelinated axons suppresses hyperexcitability following injury
eLife 5:e12661.
https://doi.org/10.7554/eLife.12661
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