Titin-based tension in the cardiac sarcomere: molecular origin and physiological adaptations.
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.
Department of Physics, University of Arizona, Tucson, AZ 85724, USA.
Brian R
BR
Anderson
Henk L
HL
Granzier
D000222:Adaptation, Physiological; D000818:Animals; D064211:Connectin / Q000737:chemistry / Q000378:metabolism*; D006321:Heart / Q000502:physiology*; D006801:Humans; D055595:Mechanical Phenomena; D012518:Sarcomeres / Q000378:metabolism*; D015398:Signal Transduction
D064211:Connectin