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

Margarita Calvo, Natalie Richards, Annina B. Schmid, Alejandro Barroso, Lan Zhu, Dinka Ivulic, Ning Zhu, Philipp Anwandter, Manzoor Bhat, Felipe A. Court, Stephen B. McMahon, David L H Bennett

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 α-DTX 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.

Original languageEnglish (US)
Article numbere12661
JournaleLife
Volume5
Issue numberAPRIL2016
DOIs
StatePublished - Apr 19 2016

Fingerprint

Potassium Channels
Axons
Wounds and Injuries
Chemical analysis
Shaker Superfamily of Potassium Channels
Neuroma
Myelinated Nerve Fibers
Peripheral Nerve Injuries
Spinal Nerve Roots
Rats
Neuralgia
Fibers

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)
  • Neuroscience(all)

Cite this

Calvo, M., Richards, N., Schmid, A. B., Barroso, A., Zhu, L., Ivulic, D., ... Bennett, D. L. H. (2016). Altered potassium channel distribution and composition in myelinated axons suppresses hyperexcitability following injury. eLife, 5(APRIL2016), [e12661]. https://doi.org/10.7554/eLife.12661

Altered potassium channel distribution and composition in myelinated axons suppresses hyperexcitability following injury. / Calvo, Margarita; Richards, Natalie; Schmid, Annina B.; Barroso, Alejandro; Zhu, Lan; Ivulic, Dinka; Zhu, Ning; Anwandter, Philipp; Bhat, Manzoor; Court, Felipe A.; McMahon, Stephen B.; Bennett, David L H.

In: eLife, Vol. 5, No. APRIL2016, e12661, 19.04.2016.

Research output: Contribution to journalArticle

Calvo, M, Richards, N, Schmid, AB, Barroso, A, Zhu, L, Ivulic, D, Zhu, N, Anwandter, P, Bhat, M, Court, FA, McMahon, SB & Bennett, DLH 2016, 'Altered potassium channel distribution and composition in myelinated axons suppresses hyperexcitability following injury', eLife, vol. 5, no. APRIL2016, e12661. https://doi.org/10.7554/eLife.12661
Calvo, Margarita ; Richards, Natalie ; Schmid, Annina B. ; Barroso, Alejandro ; Zhu, Lan ; Ivulic, Dinka ; Zhu, Ning ; Anwandter, Philipp ; Bhat, Manzoor ; Court, Felipe A. ; McMahon, Stephen B. ; Bennett, David L H. / Altered potassium channel distribution and composition in myelinated axons suppresses hyperexcitability following injury. In: eLife. 2016 ; Vol. 5, No. APRIL2016.
@article{63c4e395c62843af9d4b721af3ad545a,
title = "Altered potassium channel distribution and composition in myelinated axons suppresses hyperexcitability following injury",
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 na{\"i}ve 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 α-DTX 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.",
author = "Margarita Calvo and Natalie Richards and Schmid, {Annina B.} and Alejandro Barroso and Lan Zhu and Dinka Ivulic and Ning Zhu and Philipp Anwandter and Manzoor Bhat and Court, {Felipe A.} and McMahon, {Stephen B.} and Bennett, {David L H}",
year = "2016",
month = "4",
day = "19",
doi = "10.7554/eLife.12661",
language = "English (US)",
volume = "5",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
number = "APRIL2016",

}

TY - JOUR

T1 - Altered potassium channel distribution and composition in myelinated axons suppresses hyperexcitability following injury

AU - Calvo, Margarita

AU - Richards, Natalie

AU - Schmid, Annina B.

AU - Barroso, Alejandro

AU - Zhu, Lan

AU - Ivulic, Dinka

AU - Zhu, Ning

AU - Anwandter, Philipp

AU - Bhat, Manzoor

AU - Court, Felipe A.

AU - McMahon, Stephen B.

AU - Bennett, David L H

PY - 2016/4/19

Y1 - 2016/4/19

N2 - 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 α-DTX 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.

AB - 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 α-DTX 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.

UR - http://www.scopus.com/inward/record.url?scp=84964502511&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84964502511&partnerID=8YFLogxK

U2 - 10.7554/eLife.12661

DO - 10.7554/eLife.12661

M3 - Article

C2 - 27033551

AN - SCOPUS:84964502511

VL - 5

JO - eLife

JF - eLife

SN - 2050-084X

IS - APRIL2016

M1 - e12661

ER -