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 A. Bhat; Felipe A. Court; Stephen B. McMahon; David L H Bennett

doi:10.7554/eLife.12661

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 A. Bhat, Felipe A. Court, Stephen B. McMahon, David L H Bennett

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

37 Citations (Scopus)

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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 language	English
Article number	e12661
Pages (from-to)	1-26
Journal	eLife
Volume	5
Issue number	APRIL2016
Early online date	1 Apr 2016
DOIs	https://doi.org/10.7554/eLife.12661
Publication status	Published - 19 Apr 2016

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10.7554/eLife.12661Licence: CC BY

Alteredpotassiumchanneldistribution_CALVO_Accepted15March2016_GOLDFPVFinal published version, 3.39 MBLicence: CC BY

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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 Bhat, {Manzoor A.} and Court, {Felipe A.} and McMahon, {Stephen B.} and Bennett, {David L H}",

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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 A.

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.

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

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