title: Decreased force enhancement in skeletal muscle sarcomeres with a deletion in titin.
abstract: In the cross-bridge theory, contractile force is produced by cross-bridges that form between actin and myosin filaments. However, when a contracting muscle is stretched, its active force vastly exceeds the force that can be attributed to cross-bridges. This unexplained, enhanced force has been thought to originate in the giant protein titin, which becomes stiffer in actively compared with passively stretched sarcomeres by an unknown mechanism. We investigated this mechanism using a genetic mutation (mdm) with a small but crucial deletion in the titin protein. Myofibrils from normal and mdm mice were stretched from sarcomere lengths of 2.5 to 6.0 μm. Actively stretched myofibrils from normal mice were stiffer and generated more force than passively stretched myofibrils at all sarcomere lengths. No increase in stiffness and just a small increase in force were observed in actively compared with passively stretched mdm myofibrils. These results are in agreement with the idea that titin force enhancement stiffens and stabilizes the sarcomere during contraction and that this mechanism is lost with the mdm mutation.
authors.affiliation: Human Performance Laboratory, Department of Kinesiology, University of Calgary, KNB 404 2500 University Drive NW, Calgary, Alberta, Canada T2N 1N4 wherzog@ucalgary.ca.
authors.forename: Krysta
authors.initials: K
authors.lastname: Powers
authors.affiliation: Department of Biological Sciences, Northern Arizona University, 617 S. Beaver Street, Biological Sciences, Building 21, Flagstaff, AZ 86001, USA.
authors.forename: Kiisa
authors.initials: K
authors.lastname: Nishikawa
authors.affiliation: Human Performance Laboratory, Department of Kinesiology, University of Calgary, KNB 404 2500 University Drive NW, Calgary, Alberta, Canada T2N 1N4.
authors.forename: Venus
authors.initials: V
authors.lastname: Joumaa
authors.affiliation: Human Performance Laboratory, Department of Kinesiology, University of Calgary, KNB 404 2500 University Drive NW, Calgary, Alberta, Canada T2N 1N4.
authors.forename: Walter
authors.initials: W
authors.lastname: Herzog
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D064211:Connectin / Q000235:genetics* / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology*; D009136:Muscular Dystrophies / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009220:Myositis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012518:Sarcomeres / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017384:Sequence Deletion
chemical_list: D064211:Connectin
keywords: Cross-bridges; Eccentric contractions; Muscular dystrophy with myositis; Myofibrils; Stiffness