Titin-based tension in the cardiac sarcomere: molecular origin and physiological adaptations

Prog Biophys Mol Biol. Oct-Nov 2012;110(2-3):204-17. doi: 10.1016/j.pbiomolbio.2012.08.003. Epub 2012 Aug 11.

Abstract

The passive stiffness of cardiac muscle plays a critical role in ventricular filling during diastole and is determined by the extracellular matrix and the sarcomeric protein titin. Titin spans from the Z-disk to the M-band of the sarcomere and also contains a large extensible region that acts as a molecular spring and develops passive force during sarcomere stretch. This extensible segment is titin's I-band region, and its force-generating mechanical properties determine titin-based passive tension. The properties of titin's I-band region can be modulated by isoform splicing and post-translational modification and are intimately linked to diastolic function. This review discusses the physical origin of titin-based passive tension, the mechanisms that alter titin stiffness, and titin's role in stress-sensing signaling pathways.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptation, Physiological*
  • Animals
  • Connectin / chemistry
  • Connectin / metabolism*
  • Heart / physiology*
  • Humans
  • Mechanical Phenomena*
  • Sarcomeres / metabolism*
  • Signal Transduction

Substances

  • Connectin