Titin force is enhanced in actively stretched skeletal muscle

Krysta Powers, Gudrun Schappacher-Tilp, Azim Jinha, Tim Leonard, Kiisa C Nishikawa, Walter Herzog

Research output: Contribution to journalArticle

53 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)3629-3636
Number of pages8
JournalJournal of Experimental Biology
Volume217
Issue number20
DOIs
StatePublished - Oct 1 2014

Fingerprint

Connectin
skeletal muscle
Skeletal Muscle
muscle
calcium
sliding
protein
Myofibrils
contraction
animal models
myofibrils
Calcium
Muscles
Sarcomeres
Calcium-Binding Proteins
animal
Muscle Contraction
calcium-binding proteins
muscles
sarcomeres

Keywords

  • Crossbridge theory
  • Eccentric contractions
  • Force enhancement
  • Skeletal muscle
  • Titin

ASJC Scopus subject areas

  • Animal Science and Zoology
  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Physiology
  • Insect Science
  • Aquatic Science

Cite this

Powers, K., Schappacher-Tilp, G., Jinha, A., Leonard, T., Nishikawa, K. C., & Herzog, W. (2014). Titin force is enhanced in actively stretched skeletal muscle. Journal of Experimental Biology, 217(20), 3629-3636. https://doi.org/10.1242/jeb.105361

Titin force is enhanced in actively stretched skeletal muscle. / Powers, Krysta; Schappacher-Tilp, Gudrun; Jinha, Azim; Leonard, Tim; Nishikawa, Kiisa C; Herzog, Walter.

In: Journal of Experimental Biology, Vol. 217, No. 20, 01.10.2014, p. 3629-3636.

Research output: Contribution to journalArticle

Powers, K, Schappacher-Tilp, G, Jinha, A, Leonard, T, Nishikawa, KC & Herzog, W 2014, 'Titin force is enhanced in actively stretched skeletal muscle', Journal of Experimental Biology, vol. 217, no. 20, pp. 3629-3636. https://doi.org/10.1242/jeb.105361
Powers K, Schappacher-Tilp G, Jinha A, Leonard T, Nishikawa KC, Herzog W. Titin force is enhanced in actively stretched skeletal muscle. Journal of Experimental Biology. 2014 Oct 1;217(20):3629-3636. https://doi.org/10.1242/jeb.105361
Powers, Krysta ; Schappacher-Tilp, Gudrun ; Jinha, Azim ; Leonard, Tim ; Nishikawa, Kiisa C ; Herzog, Walter. / Titin force is enhanced in actively stretched skeletal muscle. In: Journal of Experimental Biology. 2014 ; Vol. 217, No. 20. pp. 3629-3636.
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