Contractile Performance and Energy Utilization of Skeletal Muscle; Creatine Kinase and Acto-myosin ATPase

Simple item page
dc.contributor.authorMelnyk, Jason Alexanderen
dc.contributor.committeechairWilliams, Jay H.en
dc.contributor.committeememberDavy, Kevin P.en
dc.contributor.committeememberMoore, David M.en
dc.contributor.committeememberNewton, William E.en
dc.contributor.committeememberRankin, Janet L. Walbergen
dc.contributor.departmentHuman Nutrition, Foods, and Exerciseen
dc.date.accessioned2014-03-14T20:07:09Zen
dc.date.adate2009-02-17en
dc.date.available2014-03-14T20:07:09Zen
dc.date.issued2009-01-23en
dc.date.rdate2012-06-22en
dc.date.sdate2009-02-04en
dc.description.abstractCreatine kinase (CK) primarily serves as an energy buffer assisting in regulating ATP homeostasis through synthesis of ATP from ADP and phosphocreatine (PCr). This enzyme is bound in the sarcomere near sites of ATP consumption via acto-myosin ATPase (A‧M‧ATPase) and research in cardiac muscle has found that PCr can alter contractile performance (maximal isometric force and Ca²⁺ sensitivity). Based on this evidence, CK and A‧M‧ATPase may be coupled in skeletal muscle. Therefore the purpose of this investigation was to determine the influence of the CK system on contractile performance and energy utilization in skeletal muscle. When skinned fibers (membrane removed) were provided a limited supply of [ATP] (0.1 mM), this resulted in increased Ca²⁺ sensitivity. The addition of PCr to low ATP solutions restored Ca²⁺ sensitivity and allowed normal isometric force generation across a range of [Ca²⁺] via ATP synthesis by CK. This was also possible with only CK reaction substrates (ADP, PCr) in the absence of ATP. Based on these findings, endogenous CK activity in glycerol skinned skeletal muscle fibers is sufficient to permit normal function of the contractile apparatus. Energy utilization was studied by indirect assessment of ADP production. Decreased net ADP production as measured by NADH fluorescence revealed endogenous CK was able to convert ADP produced by A‧M‧ATPase to ATP in skeletal muscle across a range of both [Ca²⁺] and [ATP]. This was confirmed directly via high-performance liquid chromatography measurements of ATP and ADP by showing that skinned skeletal muscle bundles have sufficient endogenous CK activity to produce ATP from substrates (ADP, PCr) and the ability to maintain low [ADP] in the presence of PCr. This study adds to the evidence for specific compartmentation of CK near sites of ATP utilization and contributes to the body of knowledge on contractile performance in skinned skeletal muscle fibers. By showing how changing demands on skeletal muscle (through increased Ca²⁺) alters force production and Ca²⁺ sensitivity, these findings lend support for the importance of endogenous CK as a pathway of ATP regeneration in skeletal muscle.en
dc.description.degreePh. D.en
dc.identifier.otheretd-02042009-200044en
dc.identifier.sourceurlhttp://scholar.lib.vt.edu/theses/available/etd-02042009-200044/en
dc.identifier.urihttp://hdl.handle.net/10919/26116en
dc.publisherVirginia Techen
dc.relation.haspartETDMelnykv2.pdfen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectcontractile performanceen
dc.subjectmuscle energeticsen
dc.titleContractile Performance and Energy Utilization of Skeletal Muscle; Creatine Kinase and Acto-myosin ATPaseen
dc.typeDissertationen
thesis.degree.disciplineHuman Nutrition, Foods, and Exerciseen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.leveldoctoralen
thesis.degree.namePh. D.en
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
ETDMelnykv2.pdf
Size:
1.39 MB
Format:
Adobe Portable Document Format
Download
Collections
Doctoral Dissertations