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AuthorChaiklieng, Sunisadc.contributor.author
Date of accession2016-03-14T15:21:57Zdc.date.accessioned
Available in OPARU since2016-03-14T15:21:57Zdc.date.available
Year of creation2007dc.date.created
AbstractMutations in the chloride channel are causative for low chloride conductance (gCl-) myotonia. The phenotype shows muscle stiffness. By unknown mechanisms, this type of myotonia shows a reduction of stiffness after exercise, the so-called warm-up phenomenon. This study investigated myotonic stiffness and the warm-up phenomenon in vitro. Mechanographic registrations and resting membrane potential measurements were performed. Muscle samples from the animal model for low gCl-myotonia (ADR-mice) as well as pharmacologically induced myotonia were studied. The [K+]o and osmolarity were varied and pharmacological substances with potential clinical benefit were tested. Strong contraction triggers K+ accumulation in the small T-tubular compartment which is capable to initiate myotonic bursts, thereby prolonging muscle relaxation (myotonic stiffness). Further increase in K+ and the osmolarity led to a sustained membrane depolarization in a concentration-dependent manner. At 7 mM [K+]o the myotonic burst rate was suppressed more than 90 %. Repetitive contractions facilitated the warm-up phenomenon reflecting an enhanced stabilization of the membrane excitability. The big conductance calcium activated potassium channel (BK) agonist NS1608 led to a more severe relaxation deficit, but also to a more rapid onset of warm-up. Blocking the BK channel with paxilline prevented the onset of myotonia. Increasing gK+ via activation of the voltage gated potassium channels by retigabine enhanced the warm-up phenomenon. The sodium potassium chloride cotransporter type 1 inhibitor bumetanide prevented the depolarization and reversed the antimyotonic effect of high osmolarity. Blocking voltage gated Na+ channels with mexiletine and flecainide dose-dependently facilitated the warm-up phenomenon in ADR muscle. The findings have an important impact on dietary counseling and the use of drugs influencing gK+ and gNa+ to improve management and treatment of myotonic stiffness in low gCl-myotonia.dc.description.abstract
Languageendc.language.iso
PublisherUniversität Ulmdc.publisher
LicenseStandard (Fassung vom 03.05.2003)dc.rights
Link to license texthttps://oparu.uni-ulm.de/xmlui/license_v1dc.rights.uri
KeywordADRdc.subject
KeywordCIC-1dc.subject
KeywordMuscle stiffnessdc.subject
KeywordMyotonic burstsdc.subject
KeywordOsmolaritydc.subject
KeywordWarm-up phenomenondc.subject
Dewey Decimal GroupDDC 610 / Medicine & healthdc.subject.ddc
MeSHChloride channelsdc.subject.mesh
MeSHMyotoniadc.subject.mesh
MeSHOsmolar concentrationdc.subject.mesh
TitleLow chloride conductance myotonia - in vitro investigations on muscle stiffness and the warm-up phenomenondc.title
Resource typeDissertationdc.type
DOIhttp://dx.doi.org/10.18725/OPARU-1341dc.identifier.doi
URNhttp://nbn-resolving.de/urn:nbn:de:bsz:289-vts-61365dc.identifier.urn
GNDMyotoniedc.subject.gnd
FacultyMedizinische Fakultätuulm.affiliationGeneral
Date of activation2008-01-08T16:02:34Zuulm.freischaltungVTS
Peer reviewneinuulm.peerReview
Shelfmark print versionZ: J-H 11.728 ; W: W-H 9.928uulm.shelfmark
DCMI TypeTextuulm.typeDCMI
VTS-ID6136uulm.vtsID
CategoryPublikationenuulm.category
University Bibliographyjauulm.unibibliographie


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