title: Titin force is enhanced in actively stretched skeletal muscle.
abstract: The sliding filament theory of muscle contraction is widely accepted as the means by which muscles generate force during activation. Within the constraints of this theory, isometric, steady-state force produced during muscle activation is proportional to the amount of filament overlap. Previous studies from our laboratory demonstrated enhanced titin-based force in myofibrils that were actively stretched to lengths which exceeded filament overlap. This observation cannot be explained by the sliding filament theory. The aim of the present study was to further investigate the enhanced state of titin during active stretch. Specifically, we confirm that this enhanced state of force is observed in a mouse model and quantify the contribution of calcium to this force. Titin-based force was increased by up to four times that of passive force during active stretch of isolated myofibrils. Enhanced titin-based force has now been demonstrated in two distinct animal models, suggesting that modulation of titin-based force during active stretch is an inherent property of skeletal muscle. Our results also demonstrated that 15% of the enhanced state of titin can be attributed to direct calcium effects on the protein, presumably a stiffening of the protein upon calcium binding to the E-rich region of the PEVK segment and selected Ig domain segments. We suggest that the remaining unexplained 85% of this extra force results from titin binding to the thin filament. With this enhanced force confirmed in the mouse model, future studies will aim to elucidate the proposed titin-thin filament interaction in actively stretched sarcomeres.
authors.affiliation: Human Performance Laboratory, Faculty of Kinesiology, University of Calgary, AB, Canada, T2N 1N4.
authors.forename: Krysta
authors.initials: K
authors.lastname: Powers
authors.affiliation: Department for Mathematics and Scientific Computing, NAWI Graz, Karl-Franzens-University Graz, A-8010 Graz, Austria.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Schappacher-Tilp
authors.affiliation: Human Performance Laboratory, Faculty of Kinesiology, University of Calgary, AB, Canada, T2N 1N4.
authors.forename: Azim
authors.initials: A
authors.lastname: Jinha
authors.affiliation: Human Performance Laboratory, Faculty of Kinesiology, University of Calgary, AB, Canada, T2N 1N4.
authors.forename: Tim
authors.initials: T
authors.lastname: Leonard
authors.affiliation: Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ 86011-5640, USA.
authors.forename: Kiisa
authors.initials: K
authors.lastname: Nishikawa
authors.affiliation: Human Performance Laboratory, Faculty of Kinesiology, University of Calgary, AB, Canada, T2N 1N4 wherzog@ucalgary.ca.
authors.forename: Walter
authors.initials: W
authors.lastname: Herzog
mesh_terms: D008841:Actin Cytoskeleton; D000818:Animals; D001696:Biomechanical Phenomena; D002118:Calcium / Q000378:metabolism; D064211:Connectin / Q000378:metabolism / Q000502:physiology*; D003599:Cytoskeleton; D066298:In Vitro Techniques; D051379:Mice; D009119:Muscle Contraction; D009210:Myofibrils / Q000378:metabolism / Q000502:physiology*; D016658:Psoas Muscles / Q000378:metabolism / Q000502:physiology; D012518:Sarcomeres / Q000502:physiology
chemical_list: D064211:Connectin; D002118:Calcium
keywords: Cross-bridge theory; Eccentric contractions; Force enhancement; Skeletal muscle; Titin