Micromechanical Thermal Assays of Ca2+-Regulated Thin-Filament Function and Modulation by Hypertrophic Cardiomyopathy Mutants of Human Cardiac Troponin.

Microfabricated thermoelectric controllers can be employed to investigate mechanisms underlying myosin-driven sliding of Ca2+- regulated actin and disease-associated mutations in myofilament proteins. Specifically, we examined actin filament sliding—with or without human cardiac troponin (Tn) and α-...

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Published in:Journal of Biomedicine & Biotechnology Vol. 2012; pp. 1 - 14
Main Authors: Brunet, Nicolas M., Mihajlović, Goran, Aledealat, Khaled, Fang Wang, Peng Xiong, von Molnár, Stephan, Chase, P. Bryant
Format: equations & formulas pictorial research tables/charts Journal Article
Published: Wiley-Blackwell 2012
Online Access:View this record in EBSCOhost
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      dt: 2012
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      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        atl: Micromechanical Thermal Assays of Ca2+-Regulated Thin-Filament Function and Modulation by Hypertrophic Cardiomyopathy Mutants of Human Cardiac Troponin.
      aug:
        au:
          Brunet, Nicolas M.
          Mihajlović, Goran
          Aledealat, Khaled
          Fang Wang
          Peng Xiong
          von Molnár, Stephan
          Chase, P. Bryant
        affil: Department of Biological Science, Florida State University, P.O. Box 3064295, Tallahassee, FL 32306, USA; Institute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306, USA; Donders Institute for Brain, Cognition and Behavior, Centre for Cognitive Neuroimaging, Radboud University Nijmegen, 6500 HB Nijmegen, The Netherlands
      sug:
        subj:
          Calcium Metabolism
          Chemistry, Analytical
          Cardiomyopathy, Hypertrophic Familial and Genetic
          Cardiomyopathy, Hypertrophic Metabolism
          Troponin Metabolism
          Temperature
          Muscle Proteins Metabolism
          Adenosine Triphosphatase Metabolism
          Microfilament Proteins Metabolism
          Models, Biological
          Rabbits
          Animal Studies
          Human
          In Vitro Studies
          Descriptive Statistics
          Data Analysis Software
          Linear Regression
          Models, Statistical
          Funding Source
      ab: Microfabricated thermoelectric controllers can be employed to investigate mechanisms underlying myosin-driven sliding of Ca2+- regulated actin and disease-associated mutations in myofilament proteins. Specifically, we examined actin filament sliding—with or without human cardiac troponin (Tn) and α-tropomyosin (Tm)—propelled by rabbit skeletal heavy meromyosin, when temperature was varied continuously over a wide range (∼20-63°C). At the upper end of this temperature range, reversible dysregulation of thin filaments occurred at pCa 9 and 5; actomyosin function was unaffected. Tn-Tm enhanced sliding speed at pCa 5 and increased a transition temperature (Tt) between a high activation energy (Ea) but low temperature regime and a low Ea but high temperature regime. This was modulated by factors that alter cross-bridge number and kinetics. Three familial hypertrophic cardiomyopathy (FHC) mutations, cTnI R145G, cTnI K206Q, and cTnT R278C, cause dysregulation at temperatures ∼5-8°C lower; the latter two increased speed at pCa 5 at all temperatures.
      pubtype: Academic Journal
      doctype:
        equations & formulas
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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