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AuthorHoppe, Kerstindc.contributor.author
AuthorSartorius, Tinadc.contributor.author
AuthorChaiklieng, Sunisadc.contributor.author
AuthorWietzorrek, Georgdc.contributor.author
AuthorRuth, Peterdc.contributor.author
AuthorJurkat-Rott, Karindc.contributor.author
AuthorWearing, Scottdc.contributor.author
AuthorLehmann-Horn, Frankdc.contributor.author
AuthorKlingler, Wernerdc.contributor.author
Date of accession2021-10-20T14:10:23Zdc.date.accessioned
Available in OPARU since2021-10-20T14:10:23Zdc.date.available
Date of first publication2020-11-23dc.date.issued
AbstractReduced Cl− conductance causes inhibited muscle relaxation after forceful voluntary contraction due to muscle membrane hyperexcitability. This represents the pathomechanism of myotonia congenita. Due to the prevailing data suggesting that an increased potassium level is a main contributor, we studied the effect of a modulator of a big conductance Ca2+- and voltage-activated K+ channels (BK) modulator on contraction and relaxation of slow- and high-twitch muscle specimen before and after the pharmacological induction of myotonia. Human and murine muscle specimens (wild-type and BK−/−) were exposed to anthracene-9-carboxylic acid (9-AC) to inhibit CLC-1 chloride channels and to induce myotonia in-vitro. Functional effects of BK-channel activation and blockade were investigated by exposing slow-twitch (soleus) and fast-twitch (extensor digitorum longus) murine muscle specimens or human musculus vastus lateralis to an activator (NS1608) and a blocker (Paxilline), respectively. Muscle-twitch force and relaxation times (T90/10) were monitored. Compared to wild type, fast-twitch muscle specimen of BK−/− mice resulted in a significantly decreased T90/10 in presence of 9-AC. Paxilline significantly shortened T90/10 of murine slow- and fast-twitch muscles as well as human vastus lateralis muscle. Moreover, twitch force was significantly reduced after application of Paxilline in myotonic muscle. NS1608 had opposite effects to Paxilline and aggravated the onset of myotonic activity by prolongation of T90/10. The currently used standard therapy for myotonia is, in some individuals, not very effective. This in vitro study demonstrated that a BK channel blocker lowers myotonic stiffness and thus highlights its potential therapeutic option in myotonia congenital (MC).dc.description.abstract
Languageendc.language.iso
PublisherUniversität Ulmdc.publisher
LicenseCC BY 4.0 Internationaldc.rights
Link to license texthttps://creativecommons.org/licenses/by/4.0/dc.rights.uri
KeywordPaxillinedc.subject
KeywordNS1608dc.subject
KeywordRepetitive firingdc.subject
KeywordMuscle diseasedc.subject
KeywordBK channeldc.subject
Dewey Decimal GroupDDC 610 / Medicine & healthdc.subject.ddc
MeSHMyotonia congenitadc.subject.mesh
MeSHLarge-conductance calcium-activated potassium channelsdc.subject.mesh
TitlePaxilline Prevents the Onset of Myotonic Stiffness in Pharmacologically Induced Myotonia: A Preclinical Investigationdc.title
Resource typeWissenschaftlicher Artikeldc.type
SWORD Date2020-12-09T19:31:13Zdc.date.updated
VersionpublishedVersiondc.description.version
DOIhttp://dx.doi.org/10.18725/OPARU-39185dc.identifier.doi
URNhttp://nbn-resolving.de/urn:nbn:de:bsz:289-oparu-39261-0dc.identifier.urn
GNDMuskelkrankheitdc.subject.gnd
InstitutionUKU. Klinik für Anästhesiologieuulm.affiliationSpecific
InstitutionZentrum für Seltene Erkrankungen (ZSE)uulm.affiliationSpecific
Peer reviewjauulm.peerReview
DCMI TypeCollectionuulm.typeDCMI
CategoryPublikationenuulm.category
In cooperation withUniversitätsklinikum Frankfurtuulm.cooperation
In cooperation withUniversität Würzburguulm.cooperation
In cooperation withEberhard Karls Universität Tübingenuulm.cooperation
In cooperation withKhon Kaen Universityuulm.cooperation
In cooperation withMedizinische Universität Innsbruckuulm.cooperation
In cooperation withQueensland University of Technologyuulm.cooperation
In cooperation withTechnische Universität Münchenuulm.cooperation
In cooperation withKliniken SRH Landkreis Sigmaringenuulm.cooperation
DOI of original publication10.3389/fphys.2020.533946dc.relation1.doi
Source - Title of sourceFrontiers in Physiologysource.title
Source - Place of publicationFrontiers Mediasource.publisher
Source - Volume11source.volume
Source - Year2020source.year
Source - Article number533946source.articleNumber
Source - eISSN1664-042Xsource.identifier.eissn
FundingLand Baden-Württemberguulm.funding
FundingDeutscher Akademischer Austauschdienstuulm.funding
FundingDeutsche Gesellschaft für Muskelkrankeuulm.funding
Open AccessOther Gold, Green Publisheduulm.OA
WoS000596616700001uulm.identifier.wos
Bibliographyuulmuulm.bibliographie


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