Decreased force enhancement in skeletal muscle sarcomeres with a deletion in titin

J Exp Biol. 2016 May 1;219(Pt 9):1311-6. doi: 10.1242/jeb.132027. Epub 2016 Mar 4.

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.

Keywords: Cross-bridges; Eccentric contractions; Muscular dystrophy with myositis; Myofibrils; Stiffness.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomechanical Phenomena
  • Connectin / genetics*
  • Connectin / metabolism
  • Female
  • Male
  • Mice
  • Muscle Contraction
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology*
  • Muscular Dystrophies / genetics*
  • Muscular Dystrophies / metabolism
  • Muscular Dystrophies / pathology
  • Myositis / genetics*
  • Myositis / metabolism
  • Myositis / pathology
  • Sarcomeres / genetics*
  • Sarcomeres / metabolism
  • Sarcomeres / pathology
  • Sequence Deletion*

Substances

  • Connectin

Grants and funding