After active shortening, isometric force production capacity of muscle is reduced (force depression, FD). The mechanism is incompletely understood but increasing cross-bridge detachment and/or decreasing attachment rate might be involved. Therefore we aimed to investigate the relation between work delivered during shortening (W), and change in half-relaxation time (Δ0.5RT) and change in the slow phase of muscle relaxation (Δkslow), considered as a marker for cross-bridge detachment rate, after shortening and after a short (0.7s) interruption of activation (deactivation). We hypothesized that shortening induces an accelerated relaxation related to W which is, similar to FD, largely abolished by a short deactivation. In 10 incubated supra-maximally stimulated mouse soleus muscles, we varied the amount of FD at L0 by varying shortening amplitude (0.6, 1.2 and 2.4mm). We found that W not only induces FD (R(2)=0.92) but also a dose dependent accelerated relaxation (R(2)=0.88 and R(2)=0.77 for respectively Δkslow and Δ0.5RT). In cyclic movements this is of functional significance, because the loss in force generating capacity might be (partially) compensated by faster relaxation. After a short deactivation, both FD and Δkslow were largely abolished but Δ0.5RT remained largely present. Under the assumption that Δkslow reflects a change in cross-bridge detachment rate, these results support the idea that FD is an intrinsic sarcomeric property originating from a work induced reduction of the number of force generating cross-bridges, however not via decreased attachment but via increased detachment rate.
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http://dx.doi.org/10.1016/j.jbiomech.2012.07.011 | DOI Listing |
Sports Med
November 2024
Biomechanics Laboratory, Center of Sports, Federal University of Santa Catarina, Florianópolis, Brazil.
The force-length relationship is usually obtained for isometric contractions with maximal activation, but less is known about how sarcomere length affects force during submaximal activation. During submaximal activation, length-dependent alterations in calcium sensitivity, owing to changes in cross-bridge kinetics (rate of attachment and/or detachment), result in an activation-dependent shift in optimal length to longer sarcomere lengths. It is known that sarcomere length, as well as temperature and phosphorylation of the regulatory light chains of myosin, can modify Ca⁺ sensitivity by altering the probability of cross-bridge interaction.
View Article and Find Full Text PDFAm J Physiol Heart Circ Physiol
January 2025
Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States.
The second-generation myosin activator danicamtiv (DN) has shown improved function compared with the first-generation myosin activator omecamtiv mecarbil (OM) in nonfailing myocardium by enhancing cardiac force generation but attenuating slowed relaxation. However, whether the functional improvement with DN compared with OM persists in remodeled failing myocardium remains unknown. Therefore, this study aimed to investigate the differential contractile responses to myosin activators in nonfailing and failing myocardium.
View Article and Find Full Text PDFSmall
December 2024
Institute of Molecular and Cell Physiology, Hannover Medical School, 30625, Hannover, Germany.
Myosins are ATP-powered, force-generating motor proteins involved in cardiac and muscle contraction. The external load experienced by the myosins modulates and coordinates their function in vivo. Here, this study investigates the tension-sensing mechanisms of rabbit native β-cardiac myosin (βM-II) and slow skeletal myosins (SolM-II) that perform in different physiological settings.
View Article and Find Full Text PDFJ Physiol
October 2024
Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, WA, USA.
Precise regulation of sarcomeric contraction is essential for normal cardiac function. The heart must generate sufficient force to pump blood throughout the body, but either inadequate or excessive force can lead to dysregulation and disease. Myosin regulatory light chain (RLC) is a thick-filament protein that binds to the neck of the myosin heavy chain.
View Article and Find Full Text PDFJ Muscle Res Cell Motil
September 2024
Department of Anatomy and Cell Biology, College of Medicine, University of Iowa, Iowa City, IA, 52242, USA.
We examined the integrity of flash-frozen and cryo-sectioned cardiac muscle preparations (introduced by Feng and Jin, 2020) by assessing tension transients in response to sinusoidal length changes at varying frequencies (1-100 Hz) at 25 °C. Using 70-μm-thick sections, we isolated fiber preparations to study cross-bridge (CB) kinetics: preparations were activated by saturating Ca as well as varying concentrations of ATP and phosphate (Pi). Our results showed that, compared to ordinary skinned fibers, in-series stiffness decreased to 1/2, which resulted in a decrease of isometric tension to 62%, but CB kinetics and Ca sensitivity were little affected.
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