Complementary roles of murine NaV1.7, NaV1.8 and NaV1.9 in acute itch signalling

dc.contributor.authorKühn, Helen
dc.contributor.authorKappes, Leonie
dc.contributor.authorWolf, Katharina
dc.contributor.authorGebhardt, Lisa
dc.contributor.authorNeurath, Markus F.
dc.contributor.authorReeh, Peter
dc.contributor.authorFischer, Michael J. M.
dc.contributor.authorKremer, Andreas E.
dc.date.accessioned2021-01-08
dc.date.available2021-01-01
dc.date.created2020
dc.date.issued2021-01-08
dc.description.abstractAcute pruritus occurs in various disorders. Despite severe repercussions on quality of life treatment options remain limited. Voltage-gated sodium channels (NaV) are indispensable for transformation and propagation of sensory signals implicating them as drug targets. Here, NaV1.7, 1.8 and 1.9 were compared for their contribution to itch by analysing NaV-specific knockout mice. Acute pruritus was induced by a comprehensive panel of pruritogens (C48/80, endothelin, 5-HT, chloroquine, histamine, lysophosphatidic acid, trypsin, SLIGRL, β-alanine, BAM8-22), and scratching was assessed using a magnet-based recording technology. We report an unexpected stimulus-dependent diversity in NaV channel-mediated itch signalling. NaV1.7−/− showed substantial scratch reduction mainly towards strong pruritogens. NaV1.8−/− impaired histamine and 5-HT-induced scratching while NaV1.9 was involved in itch signalling towards 5-HT, C48/80 and SLIGRL. Furthermore, similar microfluorimetric calcium responses of sensory neurons and expression of itch-related TRP channels suggest no change in sensory transduction but in action potential transformation and conduction. The cumulative sum of scratching over all pruritogens confirmed a leading role of NaV1.7 and indicated an overall contribution of NaV1.9. Beside the proposed general role of NaV1.7 and 1.9 in itch signalling, scrutiny of time courses suggested NaV1.8 to sustain prolonged itching. Therefore, NaV1.7 and 1.9 may represent targets in pruritus therapy.en
dc.identifier.citationScientific Reports 10 (2020). <https://www.nature.com/articles/s41598-020-59092-2>
dc.identifier.doihttps://doi.org/10.1038/s41598-020-59092-2
dc.identifier.opus-id15525
dc.identifier.urihttps://open.fau.de/handle/openfau/15525
dc.identifier.urnurn:nbn:de:bvb:29-opus4-155256
dc.language.isoen
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/deed.de
dc.subjectMolecular biology
dc.subjectNeuroscience
dc.subject.ddcDDC Classification::6 Technik, Medizin, angewandte Wissenschaften :: 61 Medizin und Gesundheit :: 610 Medizin und Gesundheit
dc.titleComplementary roles of murine NaV1.7, NaV1.8 and NaV1.9 in acute itch signallingen
dc.typearticle
dcterms.publisherFriedrich-Alexander-Universität Erlangen-Nürnberg (FAU)
local.journal.titleScientific Reports
local.journal.volume10
local.sendToDnbfree*
local.subject.fakultaetMedizinische Fakultät
local.subject.sammlungUniversität Erlangen-Nürnberg / Von der FAU geförderte Open Access Artikel / Von der FAU geförderte Open Access Artikel 2020
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