Changes in Ionic Conductance Signature of Nociceptive Neurons Underlying Fabry Disease Phenotype
The first symptom arising in many Fabry patients is neuropathic pain due to changes in small myelinated and unmyelinated fibers in the periphery, which is subsequently followed by a loss of sensory perception. Here we studied changes in the peripheral nervous system of Fabry patients and a Fabry mou...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-07-01
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| Series: | Frontiers in Neurology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fneur.2017.00335/full |
| _version_ | 1818862772956430336 |
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| author | Barbara Namer Barbara Namer Kirstin Ørstavik Roland Schmidt Norbert Mair Inge Petter Kleggetveit Maximillian Zeidler Theresa Martha Ellen Jorum Ellen Jorum Martin Schmelz Theodora Kalpachidou Michaela Kress Michiel Langeslag |
| author_facet | Barbara Namer Barbara Namer Kirstin Ørstavik Roland Schmidt Norbert Mair Inge Petter Kleggetveit Maximillian Zeidler Theresa Martha Ellen Jorum Ellen Jorum Martin Schmelz Theodora Kalpachidou Michaela Kress Michiel Langeslag |
| author_sort | Barbara Namer |
| collection | DOAJ |
| description | The first symptom arising in many Fabry patients is neuropathic pain due to changes in small myelinated and unmyelinated fibers in the periphery, which is subsequently followed by a loss of sensory perception. Here we studied changes in the peripheral nervous system of Fabry patients and a Fabry mouse model induced by deletion of α-galactosidase A (Gla−/0). The skin innervation of Gla−/0 mice resembles that of the human Fabry patients. In Fabry diseased humans and Gla−/0 mice, we observed similar sensory abnormalities, which were also observed in nerve fiber recordings in both patients and mice. Electrophysiological recordings of cultured Gla−/0 nociceptors revealed that the conductance of voltage-gated Na+ and Ca2+ currents was decreased in Gla−/0 nociceptors, whereas the activation of voltage-gated K+ currents was at more depolarized potentials. Conclusively, we have observed that reduced sensory perception due to small-fiber degeneration coincides with altered electrophysiological properties of sensory neurons. |
| first_indexed | 2024-12-19T10:05:11Z |
| format | Article |
| id | doaj.art-6aff7a286f8d4e43ac59e3848767c5b7 |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-12-19T10:05:11Z |
| publishDate | 2017-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-6aff7a286f8d4e43ac59e3848767c5b72022-12-21T20:26:31ZengFrontiers Media S.A.Frontiers in Neurology1664-22952017-07-01810.3389/fneur.2017.00335278252Changes in Ionic Conductance Signature of Nociceptive Neurons Underlying Fabry Disease PhenotypeBarbara Namer0Barbara Namer1Kirstin Ørstavik2Roland Schmidt3Norbert Mair4Inge Petter Kleggetveit5Maximillian Zeidler6Theresa Martha7Ellen Jorum8Ellen Jorum9Martin Schmelz10Theodora Kalpachidou11Michaela Kress12Michiel Langeslag13Department of Physiology and Pathophysiology, University of Erlangen-Nuremberg, Erlangen, GermanyDepartment of Anesthesiology, Heidelberg University, Mannheim, GermanySection of Clinical Neurophysiology, Department of Neurology, Oslo University Hospital Rikshospitalet, Oslo, NorwayDepartment of Clinical Neurophysiology, Uppsala University Hospital, Uppsala, SwedenDepartment of Physiology and Medical Physics, Division of Physiology, Medical University of Innsbruck, Innsbruck, AustriaSection of Clinical Neurophysiology, Department of Neurology, Oslo University Hospital Rikshospitalet, Oslo, NorwayDepartment of Physiology and Medical Physics, Division of Physiology, Medical University of Innsbruck, Innsbruck, AustriaDepartment of Physiology and Medical Physics, Division of Physiology, Medical University of Innsbruck, Innsbruck, AustriaDepartment of Anesthesiology, Heidelberg University, Mannheim, GermanyFaculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, NorwayDepartment of Anesthesiology, Heidelberg University, Mannheim, GermanyDepartment of Physiology and Medical Physics, Division of Physiology, Medical University of Innsbruck, Innsbruck, AustriaDepartment of Physiology and Medical Physics, Division of Physiology, Medical University of Innsbruck, Innsbruck, AustriaDepartment of Physiology and Medical Physics, Division of Physiology, Medical University of Innsbruck, Innsbruck, AustriaThe first symptom arising in many Fabry patients is neuropathic pain due to changes in small myelinated and unmyelinated fibers in the periphery, which is subsequently followed by a loss of sensory perception. Here we studied changes in the peripheral nervous system of Fabry patients and a Fabry mouse model induced by deletion of α-galactosidase A (Gla−/0). The skin innervation of Gla−/0 mice resembles that of the human Fabry patients. In Fabry diseased humans and Gla−/0 mice, we observed similar sensory abnormalities, which were also observed in nerve fiber recordings in both patients and mice. Electrophysiological recordings of cultured Gla−/0 nociceptors revealed that the conductance of voltage-gated Na+ and Ca2+ currents was decreased in Gla−/0 nociceptors, whereas the activation of voltage-gated K+ currents was at more depolarized potentials. Conclusively, we have observed that reduced sensory perception due to small-fiber degeneration coincides with altered electrophysiological properties of sensory neurons.http://journal.frontiersin.org/article/10.3389/fneur.2017.00335/fullFabry diseaselysosomal storage disordersingle fiber recordingsneuronal excitabilityelectrophysiologynociception |
| spellingShingle | Barbara Namer Barbara Namer Kirstin Ørstavik Roland Schmidt Norbert Mair Inge Petter Kleggetveit Maximillian Zeidler Theresa Martha Ellen Jorum Ellen Jorum Martin Schmelz Theodora Kalpachidou Michaela Kress Michiel Langeslag Changes in Ionic Conductance Signature of Nociceptive Neurons Underlying Fabry Disease Phenotype Frontiers in Neurology Fabry disease lysosomal storage disorder single fiber recordings neuronal excitability electrophysiology nociception |
| title | Changes in Ionic Conductance Signature of Nociceptive Neurons Underlying Fabry Disease Phenotype |
| title_full | Changes in Ionic Conductance Signature of Nociceptive Neurons Underlying Fabry Disease Phenotype |
| title_fullStr | Changes in Ionic Conductance Signature of Nociceptive Neurons Underlying Fabry Disease Phenotype |
| title_full_unstemmed | Changes in Ionic Conductance Signature of Nociceptive Neurons Underlying Fabry Disease Phenotype |
| title_short | Changes in Ionic Conductance Signature of Nociceptive Neurons Underlying Fabry Disease Phenotype |
| title_sort | changes in ionic conductance signature of nociceptive neurons underlying fabry disease phenotype |
| topic | Fabry disease lysosomal storage disorder single fiber recordings neuronal excitability electrophysiology nociception |
| url | http://journal.frontiersin.org/article/10.3389/fneur.2017.00335/full |
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