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AuthorPan, Yuandc.contributor.author
Date of accession2020-01-31T16:51:31Zdc.date.accessioned
Available in OPARU since2020-01-31T16:51:31Zdc.date.available
Year of creation2019dc.date.created
Date of first publication2020-01-31dc.date.issued
AbstractThe control of calcium release in the mammalian skeletal muscle excitation-contraction coupling (e-c coupling) involves two Ca2+ ion channels: the L-type Ca2+ channel (Cav1.1) or dihydropyridine receptor (DHPR) and the ryanodine receptor type 1 (RyR1). The interaction between them is a conformational coupling, while the voltage gated DHPR serves as the voltage sensor of the RyR1. Mutations in these two ion channels can cause alterations or disruptions in e-c coupling. In this dissertation, two murine models, one carrying a mutation in the pore loop of the DHPR and one carrying a mutation in the RyR1 were studied. Voltage clamp experiments showed that the mutation N617D in the DHPR selectivity filter region eliminated the L-type Ca2+ current. Measurements using a fluorescent indicator demonstrated that Ca2+ release properties, as well as the sarcoplasmic reticulum (SR) Ca2+ content, were unaffected. Interestingly, the mutation altered the voltage dependence of the channel inactivation at low external Ca2+ concentration. The Y524S mutation in RyR1 is malignant hyperthermia causative and has been shown to cause alterations in Ca2+ release properties and channel inactivation. Here a possible retrograde Ca2+ release effect on Cav1.1 was investigated using SR depletion conditions and strong Ca2+ buffering. Despite experimental conditions that are known to effectively reduce local Ca2+ transients, the previously reported change in the calcium current inactivation persisted. The results indicate that voltage-activated Ca2+ release does not mediate retrograde modulation of inactivation in skeletal muscle e-c coupling of Y524S mice.dc.description.abstract
Languageendc.language.iso
PublisherUniversität Ulmdc.publisher
LicenseStandarddc.rights
Link to license texthttps://oparu.uni-ulm.de/xmlui/license_v3dc.rights.uri
KeywordSkeletal muscledc.subject
KeywordExcitation-contraction couplingdc.subject
KeywordCa2+ signalingdc.subject
KeywordInactivationdc.subject
KeywordTransgenic mousedc.subject
Dewey Decimal GroupDDC 570 / Life sciencesdc.subject.ddc
Dewey Decimal GroupDDC 610 / Medicine & healthdc.subject.ddc
LCSHCalcium; Physiological effectdc.subject.lcsh
LCSHCellular signal transductiondc.subject.lcsh
MeSHMuscle, Skeletaldc.subject.mesh
MeSHCalcium signalingdc.subject.mesh
MeSHCalcium channelsdc.subject.mesh
MeSHMalignant hyperthermiadc.subject.mesh
TitleFunctional consequences of two critical point mutations in the skeletal muscle excitation-contraction coupling complexdc.title
Resource typeDissertationdc.type
Date of acceptance2019-10-25dcterms.dateAccepted
RefereeMelzer, Wernerdc.contributor.referee
RefereeFrick, Manfreddc.contributor.referee
DOIhttp://dx.doi.org/10.18725/OPARU-24858dc.identifier.doi
PPN1689059095dc.identifier.ppn
URNhttp://nbn-resolving.de/urn:nbn:de:bsz:289-oparu-24921-2dc.identifier.urn
GNDSkelettmuskeldc.subject.gnd
GNDCalciumdc.subject.gnd
GNDCalciumtransportdc.subject.gnd
GNDSignaltransduktiondc.subject.gnd
FacultyMedizinische Fakultätuulm.affiliationGeneral
InstitutionInstitut für Angewandte Physiologieuulm.affiliationSpecific
InstitutionInstitut für Allgemeine Physiologieuulm.affiliationSpecific
Grantor of degreeMedizinische Fakultätuulm.thesisGrantor
DCMI TypeTextuulm.typeDCMI
CategoryPublikationenuulm.category
University Bibliographyjauulm.unibibliographie


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