Altered potassium channel distribution and composition in myelinated axons suppresses hyperexcitability following injury
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 a...
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| Aineistotyyppi: | Artikkeli |
| Kieli: | English |
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eLife Sciences Publications Ltd
2016-04-01
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| Sarja: | eLife |
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| Linkit: | https://elifesciences.org/articles/12661 |
| _version_ | 1828375337230139392 |
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| author | 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 LH Bennett |
| author_facet | 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 LH Bennett |
| author_sort | Margarita Calvo |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T07:45:12Z |
| format | Article |
| id | doaj.art-6039c4bc3da94e43a48a0eb36e8c9710 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:45:12Z |
| publishDate | 2016-04-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-6039c4bc3da94e43a48a0eb36e8c97102022-12-22T02:05:21ZengeLife Sciences Publications LtdeLife2050-084X2016-04-01510.7554/eLife.12661Altered potassium channel distribution and composition in myelinated axons suppresses hyperexcitability following injuryMargarita Calvo0https://orcid.org/0000-0003-3349-9189Natalie Richards1Annina B Schmid2Alejandro Barroso3Lan Zhu4Dinka Ivulic5Ning Zhu6Philipp Anwandter7Manzoor A Bhat8Felipe A Court9Stephen B McMahon10David LH Bennett11Wolfson 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, ChileWolfson Centre for Age-Related Diseases, Kings College London, London, United KingdomSchool of Health and Rehabilitation Sciences, The University of Queensland, Brisbane, Australia; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United KingdomWolfson Centre for Age-Related Diseases, Kings College London, London, United Kingdom; Hospital Regional Universitario de Málaga. Servicio de Anestesiología, Málaga, SpainWolfson 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 KingdomDepartamento de Fisiologia, Facultad de Ciencias Biologicas- Pontificia Universidad Catolica de Chile, Santiago, ChileNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United KingdomDepartamento Ortopedia y Traumatologia, Facultad de Medicina, Pontificia Universidad Catolica de Chile, Santiago, ChileDepartment 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 StatesCenter 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, ChileWolfson Centre for Age-Related Diseases, Kings College London, London, United KingdomNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United KingdomNeuropathic 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.https://elifesciences.org/articles/12661neuropathic painneuropathyshaker type potassium channelsjuxtaparanodehypersensitivity |
| spellingShingle | 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 LH Bennett Altered potassium channel distribution and composition in myelinated axons suppresses hyperexcitability following injury eLife neuropathic pain neuropathy shaker type potassium channels juxtaparanode hypersensitivity |
| title | Altered potassium channel distribution and composition in myelinated axons suppresses hyperexcitability following injury |
| title_full | Altered potassium channel distribution and composition in myelinated axons suppresses hyperexcitability following injury |
| title_fullStr | Altered potassium channel distribution and composition in myelinated axons suppresses hyperexcitability following injury |
| title_full_unstemmed | Altered potassium channel distribution and composition in myelinated axons suppresses hyperexcitability following injury |
| title_short | Altered potassium channel distribution and composition in myelinated axons suppresses hyperexcitability following injury |
| title_sort | altered potassium channel distribution and composition in myelinated axons suppresses hyperexcitability following injury |
| topic | neuropathic pain neuropathy shaker type potassium channels juxtaparanode hypersensitivity |
| url | https://elifesciences.org/articles/12661 |
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