title: Sarcomere length dependent effects on the interaction between cTnC and cTnI in skinned papillary muscle strips.
abstract: Sarcomere length dependent activation (LDA) of myocardial force development is the cellular basis underlying the Frank-Starling law of the heart, but it is still elusive how the sarcomeres detect the length changes and convert them into altered activation of thin filament. In this study we investigated how the C-domain of cardiac troponin I (cTnI) functionally and structurally responds to the comprehensive effects of the Ca(2+), crossbridge, and sarcomere length of chemically skinned myocardial preparations. Using our in situ technique which allows for simultaneous measurements of time-resolved FRET and mechanical force of the skinned myocardial preparations, we measured changes in the FRET distance between cTnI(167C) and cTnC(89C), labeled with FRET donor and acceptor, respectively, as a function of [Ca(2+)], crossbridge state and sarcomere length of the skinned muscle preparations. Our results show that [Ca(2+)], cross-bridge feedback and sarcomere length have different effects on the structural transition of the C-domain cTnI. In particular, the interplay between crossbridges and sarcomere length has significant impacts on the functional structural change of the C-domain of cTnI in the relaxed state. These novel observations suggest the importance of the C-domain of cTnI and the dynamic and complex interplay between various components of myofilament in the LDA mechanism.
authors.affiliation: Gene and Linda Voiland School of Chemical Engineering and Bioengineering, Washington State University, Pullman, WA 99164, USA.
authors.forename: King-Lun
authors.initials: KL
authors.lastname: Li
authors.affiliation: Gene and Linda Voiland School of Chemical Engineering and Bioengineering, Washington State University, Pullman, WA 99164, USA.
authors.forename: Nazanin Bohlooli
authors.initials: NB
authors.lastname: Ghashghaee
authors.affiliation: The Department of Physiology and Biophysics, Center for Cardiovascular Research, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: R John
authors.initials: RJ
authors.lastname: Solaro
authors.affiliation: Gene and Linda Voiland School of Chemical Engineering and Bioengineering, Washington State University, Pullman, WA 99164, USA; Integrative Neuroscience Physiology, Washington State University, Pullman, WA 99164, USA. Electronic address: wdong@vetmed.wsu.edu.
authors.forename: Wenji
authors.initials: W
authors.lastname: Dong
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000737:chemistry; D031541:Fluorescence Resonance Energy Transfer; D007700:Kinetics; D015233:Models, Statistical; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D009210:Myofibrils / Q000378:metabolism; D010210:Papillary Muscles / Q000378:metabolism*; D010766:Phosphorylation; D000072417:Protein Domains; D051381:Rats; D017207:Rats, Sprague-Dawley; D012518:Sarcomeres / Q000378:metabolism*; D013314:Stress, Mechanical; D019209:Troponin C / Q000737:chemistry*; D019210:Troponin I / Q000737:chemistry*
chemical_list: D019209:Troponin C; D019210:Troponin I; D002118:Calcium
keywords: Crossbridge; Fluorescence resonance energy transfer (FRET); Sarcomere length dependent activation; Thin filament regulation; Troponin