Cellular and Molecular Bioengineering

, Volume 6, Issue 2, pp 183–198 | Cite as

Slowed Dynamics of Thin Filament Regulatory Units Reduces Ca2+-Sensitivity of Cardiac Biomechanical Function

  • Campion K. P. Loong
  • Aya K. Takeda
  • Myriam A. Badr
  • Jordan S. Rogers
  • P. Bryant ChaseEmail author


Actomyosin kinetics in both skinned skeletal muscle fibers at maximum Ca2+-activation and unregulated in vitro motility assays are modulated by solvent microviscosity in a manner consistent with a diffusion limited process. Viscosity might also influence cardiac thin filament Ca2+-regulatory protein dynamics. In vitro motility assays were conducted using thin filaments reconstituted with recombinant human cardiac troponin and tropomyosin; solvent microviscosity was varied by addition of sucrose or glucose. At saturating Ca2+, filament sliding speed (s) was inversely proportional to viscosity. Ca2+-sensitivity (pCa 50) of s decreased markedly with elevated viscosity (η/η 0 ≥ ~1.3). For comparison with unloaded motility assays, steady-state isometric force (F) and kinetics of isometric tension redevelopment (k TR) were measured in single, permeabilized porcine cardiomyocytes when viscosity surrounding the myofilaments was altered. Maximum Ca2+-activated F changed little for sucrose ≤0.3 M (η/η 0 ~ 1.4) or glucose ≤0.875 M (η/η 0 ~ 1.66), but decreased at higher concentrations. Sucrose (0.3 M) or glucose (0.875 M) decreased pCa 50 for F. k TR at saturating Ca2+ decreased steeply and monotonically with increased viscosity but there was little effect on k TR at sub-maximum Ca2+. Modeling indicates that increased solutes affect dynamics of cardiac muscle Ca2+-regulatory proteins to a much greater extent than actomyosin cross-bridge cycling.


Skinned myocyte Myosin Actin Troponin Tropomyosin In vitro motility assay Kinetics of isometric tension redevelopment Microviscosity Monosaccharide glucose Disaccharide sucrose 



This work was supported by National Institute of Health grants HL63974 (PBC), a Florida State University Center for Materials Research and Technology (MARTECH) Pre-doctoral Fellowship (MAB), and American Heart Association Pre-doctoral Fellowships 0615164B (AKT) and 0815127E (CKPL). We thank Bradley’s Country Store, Tallahassee, FL, for generously supplying porcine hearts.

Conflict of interest

The authors have no conflicts of interest to declare.


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Copyright information

© Biomedical Engineering Society 2013

Authors and Affiliations

  • Campion K. P. Loong
    • 1
    • 2
    • 4
  • Aya K. Takeda
    • 1
    • 3
    • 5
  • Myriam A. Badr
    • 1
    • 3
  • Jordan S. Rogers
    • 1
    • 6
  • P. Bryant Chase
    • 1
    Email author
  1. 1.Department of Biological ScienceThe Florida State UniversityTallahasseeUSA
  2. 2.Department of PhysicsThe Florida State UniversityTallahasseeUSA
  3. 3.Program in Molecular BiophysicsThe Florida State UniversityTallahasseeUSA
  4. 4.MathWorks, Inc.NatickUSA
  5. 5.Genaris, Inc.YokohamaJapan
  6. 6.Shands HospitalUniversity of Florida College of MedicineGainesvilleUSA

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