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 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.
authors.affiliation: Wolfson Centre for Age-Related Diseases, Kings College London, London, United Kingdom.|Departamento de Fisiologia, Facultad de Ciencias Biologicas- Pontificia Universidad Catolica de Chile, Santiago, Chile.|Departamento de Anestesiologia, Facultad de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile.
authors.forename: Margarita
authors.identifier: http://orcid.org/0000-0003-3349-9189
authors.initials: M
authors.lastname: Calvo
authors.affiliation: Wolfson Centre for Age-Related Diseases, Kings College London, London, United Kingdom.
authors.forename: Natalie
authors.initials: N
authors.lastname: Richards
authors.affiliation: School of Health and Rehabilitation Sciences, The University of Queensland, Brisbane, Australia.|Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.
authors.forename: Annina B
authors.initials: AB
authors.lastname: Schmid
authors.affiliation: Wolfson Centre for Age-Related Diseases, Kings College London, London, United Kingdom.|Hospital Regional Universitario de Málaga. Servicio de Anestesiología, Málaga, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Barroso
authors.affiliation: Wolfson Centre for Age-Related Diseases, Kings College London, London, United Kingdom.|School of Allied Health Sciences, Faculty of Health and Life Sciences, De Montfort University, Leicester, United Kingdom.
authors.forename: Lan
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Departamento de Fisiologia, Facultad de Ciencias Biologicas- Pontificia Universidad Catolica de Chile, Santiago, Chile.
authors.forename: Dinka
authors.initials: D
authors.lastname: Ivulic
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhu
authors.affiliation: Departamento Ortopedia y Traumatologia, Facultad de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile.
authors.forename: Philipp
authors.initials: P
authors.lastname: Anwandter
authors.affiliation: Department of Physiology, UT Health Science Center at San Antonio, San Antonio, United States.|School of Medicine, UT Health Science Center at San Antonio, San Antonio, United States.
authors.forename: Manzoor A
authors.initials: MA
authors.lastname: Bhat
authors.affiliation: Center for Integrative Biology, Universidad Mayor, Santiago, Chile.|FONDAP, Geroscience Center for Brain Health and Metabolism, Santiago, Chile.|Millenium Nucleus for Regenerative Biology, Pontificia Universidad Catolica de Chile, Santiago, Chile.
authors.forename: Felipe A
authors.initials: FA
authors.lastname: Court
authors.affiliation: Wolfson Centre for Age-Related Diseases, Kings College London, London, United Kingdom.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: McMahon
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.
authors.forename: David L H
authors.initials: DL
authors.lastname: Bennett
mesh_terms: D000200:Action Potentials; D000818:Animals; D001369:Axons / Q000502:physiology*; D006801:Humans; D059348:Peripheral Nerve Injuries / Q000503:physiopathology*; D051381:Rats; D051637:Shaker Superfamily of Potassium Channels / Q000378:metabolism*
chemical_list: D051637:Shaker Superfamily of Potassium Channels
keywords: human; hypersensitivity; juxtaparanode; neuropathic pain; neuropathy; neuroscience; rat; shaker type potassium channels