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.
Article and author information
Author details
Reviewing Editor
- Peggy Mason, University of Chicago, United States
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)
Version history
- Received: October 30, 2015
- Accepted: March 15, 2016
- Accepted Manuscript published: April 1, 2016 (version 1)
- 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.
Metrics
-
- 3,492
- views
-
- 724
- downloads
-
- 40
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Altered potassium channel distribution and composition in myelinated axons suppresses hyperexcitability following injury
eLife 5:e12661.
https://doi.org/10.7554/eLife.12661
Further reading
-
- Neuroscience
Probing memory of a complex visual image within a few hundred milliseconds after its disappearance reveals significantly greater fidelity of recall than if the probe is delayed by as little as a second. Classically interpreted, the former taps into a detailed but rapidly decaying visual sensory or ‘iconic’ memory (IM), while the latter relies on capacity-limited but comparatively stable visual working memory (VWM). While iconic decay and VWM capacity have been extensively studied independently, currently no single framework quantitatively accounts for the dynamics of memory fidelity over these time scales. Here, we extend a stationary neural population model of VWM with a temporal dimension, incorporating rapid sensory-driven accumulation of activity encoding each visual feature in memory, and a slower accumulation of internal error that causes memorized features to randomly drift over time. Instead of facilitating read-out from an independent sensory store, an early cue benefits recall by lifting the effective limit on VWM signal strength imposed when multiple items compete for representation, allowing memory for the cued item to be supplemented with information from the decaying sensory trace. Empirical measurements of human recall dynamics validate these predictions while excluding alternative model architectures. A key conclusion is that differences in capacity classically thought to distinguish IM and VWM are in fact contingent upon a single resource-limited WM store.
-
- Neuroscience
Our ability to recall details from a remembered image depends on a single mechanism that is engaged from the very moment the image disappears from view.
