Dataset Information

Titin-mediated thick filament activation, through a mechanosensing mechanism, introduces sarcomere-length dependencies in mathematical models of rat trabecula and whole ventricle.

ABSTRACT: Recent experimental evidence in skeletal muscle demonstrated the existence of a thick-filament mechanosensing mechanism, acting as a second regulatory system for muscle contraction, in addition to calcium-mediated thin filament regulation. These two systems cooperate to generate force, but the extent to which their interaction is relevant in physiologically contracting muscle was not yet assessed experimentally. Therefore, we included both regulatory mechanisms in a mathematical model of rat trabecula and whole ventricle. No additional regulatory mechanisms were considered in our model. Our simulations suggested that mechanosensing regulation is not limited to the initial phases of contraction but, instead, is crucial during physiological contraction. An important consequence of this finding is that titin mediated thick filament activation can account for several sarcomere length dependencies observed in contracting muscle. Under the hypothesis that a similar mechanism is acting on cardiac muscle, and within the limits of a finite element left ventricle model, we predict that these two regulatory mechanisms are crucial for the molecular basis of the Frank-Starling law of the heart.

SUBMITTER: Marcucci L

PROVIDER: S-EPMC5514028 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Titin-mediated thick filament activation, through a mechanosensing mechanism, introduces sarcomere-length dependencies in mathematical models of rat trabecula and whole ventricle.

Marcucci Lorenzo L Washio Takumi T Yanagida Toshio T

Scientific reports 20170717 1

Recent experimental evidence in skeletal muscle demonstrated the existence of a thick-filament mechanosensing mechanism, acting as a second regulatory system for muscle contraction, in addition to calcium-mediated thin filament regulation. These two systems cooperate to generate force, but the extent to which their interaction is relevant in physiologically contracting muscle was not yet assessed experimentally. Therefore, we included both regulatory mechanisms in a mathematical model of rat tra ...[more]

PMID: 28717163

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Project description:We studied the effect of titin-based passive tension on sarcomere structure by simultaneously measuring passive tension and low-angle x-ray diffraction patterns on passive fiber bundles from rabbit skinned psoas muscle. We used a stretch-hold-release protocol with measurement of x-ray diffraction patterns at various passive tension levels during the hold phase before and after passive stress relaxation. Measurements were performed in relaxing solution without and with dextran T-500 to compress the lattice toward physiological levels. The myofilament lattice spacing was measured in the A-band (d(1,0)) and Z-disk (d(Z)) regions of the sarcomere. The axial spacing of the thick-filament backbone was determined from the sixth myosin meridional reflection (M6) and the equilibrium positions of myosin heads from the fourth myosin layer line peak position and the I(1,1)/I(1,0) intensity ratio. Total passive tension was measured during the x-ray experiments, and a differential extraction technique was used to determine the relations between collagen- and titin-based passive tension and sarcomere length. Within the employed range of sarcomere lengths (?2.2-3.4 ?m), titin accounted for >80% of passive tension. X-ray results indicate that titin compresses both the A-band and Z-disk lattice spacing with viscoelastic behavior when fibers are swollen after skinning, and elastic behavior when the lattice is reduced with dextran. Titin also increases the axial thick-filament spacing, M6, in an elastic manner in both the presence and absence of dextran. No changes were detected in either I(1,1)/I(1,0) or the position of peaks on the fourth myosin layer line during passive stress relaxation. Passive tension and M6 measurements were converted to thick-filament compliance, yielding a value of ?85 m/N, which is several-fold larger than the thick-filament compliance determined by others during the tetanic tension plateau of activated intact muscle. This difference can be explained by the fact that thick filaments are more compliant at low tension (passive muscle) than at high tension (tetanic tension). The implications of our findings are discussed.

Dataset Information

Titin-mediated thick filament activation, through a mechanosensing mechanism, introduces sarcomere-length dependencies in mathematical models of rat trabecula and whole ventricle.

Publications

Titin-mediated thick filament activation, through a mechanosensing mechanism, introduces sarcomere-length dependencies in mathematical models of rat trabecula and whole ventricle.

Similar Datasets

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