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Cross-Bridges and Sarcomeric Non-cross-bridge Structures Contribute to Increased Work in Stretch-Shortening Cycles.

ABSTRACT: Stretch-shortening cycles (SSCs) refer to the muscle action when an active muscle stretch is immediately followed by active muscle shortening. This combination of eccentric and concentric contractions is the most important type of daily muscle action and plays a significant role in natural locomotion such as walking, running or jumping. SSCs are used in human and animal movements especially when a high movement speed or economy is required. A key feature of SSCs is the increase in muscular force and work during the concentric phase of a SSC by more than 50% compared with concentric muscle actions without prior stretch (SSC-effect). This improved muscle capability is related to various mechanisms, including pre-activation, stretch-reflex responses and elastic recoil from serial elastic tissues. Moreover, it is assumed that a significant contribution to enhanced muscle capability lies in the sarcomeres itself. Thus, we investigated the force output and work produced by single skinned fibers of rat soleus muscles during and after ramp contractions at a constant velocity. Shortening, lengthening, and SSCs were performed under physiological boundary conditions with 85% of the maximum shortening velocity and stretch-shortening magnitudes of 18% of the optimum muscle length. The different contributions of cross-bridge (XB) and non-cross-bridge (non-XB) structures to the total muscle force were identified by using Blebbistatin. The experiments revealed three main results: (i) partial detachment of XBs during the eccentric phase of a SSC, (ii) significantly enhanced forces and mechanical work during the concentric phase of SSCs compared with shortening contractions with and without XB-inhibition, and (iii) no residual force depression after SSCs. The results obtained by administering Blebbistatin propose a titin-actin interaction that depends on XB-binding or active XB-based force production. The findings of this study further suggest that enhanced forces generated during the active lengthening phase of SSCs persist during the subsequent shortening phase, thereby contributing to enhanced work. Accordingly, our data support the hypothesis that sarcomeric mechanisms related to residual force enhancement also contribute to the SSC-effect. The preload of the titin molecule, acting as molecular spring, might be part of that mechanism by increasing the mechanical efficiency of work during physiological SSCs.

SUBMITTER: Tomalka A

PROVIDER: S-EPMC7399218 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The sliding filament-swinging cross bridge theory of skeletal muscle contraction provides a reasonable description of muscle properties during isometric contractions at or near maximum isometric force. However, it fails to predict muscle force during dynamic length changes, implying that the model is not complete. Mounting evidence suggests that, along with cross bridges, a Ca2+-sensitive viscoelastic element, likely the titin protein, contributes to muscle force and work. The purpose of this study was to develop a multi-level approach deploying stretch-shortening cycles (SSCs) to test the hypothesis that, along with cross bridges, Ca2+-sensitive viscoelastic elements in sarcomeres contribute to force and work. Using whole soleus muscles from wild type and mdm mice, which carry a small deletion in the N2A region of titin, we measured the activation- and phase-dependence of enhanced force and work during SSCs with and without doublet stimuli. In wild type muscles, a doublet stimulus led to an increase in peak force and work per cycle, with the largest effects occurring for stimulation during the lengthening phase of SSCs. In contrast, mdm muscles showed neither doublet potentiation features, nor phase-dependence of activation. To further distinguish the contributions of cross bridge and non-cross bridge elements, we performed SSCs on permeabilized psoas fiber bundles activated to different levels using either [Ca2+] or [Ca2+] plus the myosin inhibitor 2,3-butanedione monoxime (BDM). Across activation levels ranging from 15 to 100% of maximum isometric force, peak force, and work per cycle were enhanced for fibers in [Ca2+] plus BDM compared to [Ca2+] alone at a corresponding activation level, suggesting a contribution from Ca2+-sensitive, non-cross bridge, viscoelastic elements. Taken together, our results suggest that a tunable viscoelastic element such as titin contributes to: (1) persistence of force at low [Ca2+] in doublet potentiation; (2) phase- and length-dependence of doublet potentiation observed in wild type muscles and the absence of these effects in mdm muscles; and (3) increased peak force and work per cycle in SSCs. We conclude that non-cross bridge viscoelastic elements, likely titin, contribute substantially to muscle force and work, as well as the phase-dependence of these quantities, during dynamic length changes.

Project description:It has been shown that not only calcium but also strong binding myosin heads contribute to thin filament activation in isometrically contracting animal fast-twitch and cardiac muscle preparations. This behavior has not been studied in human muscle fibers or animal slow-twitch fibers. Human slow-twitch fibers are interesting since they contain the same myosin heavy chain isoform as the human heart. To explore myosin-induced activation of the thin filament in isometrically contracting human slow-twitch fibers, the endogenous troponin complex was exchanged for a well-characterized fast-twitch skeletal troponin complex labeled with the fluorescent dye N-((2-(Iodoacetoxy)ethyl)-N-methyl)amino-7-nitrobenz-2-oxa-1,3-diazole (fsTn-IANBD). The exchange was ?70% complete (n = 8). The relative contributions of calcium and strong binding cross-bridges to thin filament activation were dissected by increasing the concentration of calcium from relaxing (pCa 7.5) to saturating levels (pCa 4.5) before and after incubating the exchanged fibers in the myosin inhibitor para-aminoblebbistatin (AmBleb). At pCa 4.5, the relative contributions of calcium and strong binding cross-bridges to thin filament activation were ?69 and ?31%, respectively. Additionally, switching from isometric to isotonic contraction at pCa 4.5 revealed that strong binding cross-bridges contributed ?29% to thin filament activation (i.e., virtually the same magnitude obtained with AmBleb). Thus, we showed through two different approaches that lowering the number of strong binding cross-bridges, at saturating calcium, significantly reduced the activation of the thin filament in human slow-twitch fibers. The contribution of myosin to activation resembled that which was previously reported in rat cardiac and rabbit fast-twitch muscle preparations. This method could be applied to slow-twitch human fibers obtained from the soleus muscle of cardiomyopathy patients. Such studies could lead to a better understanding of the effect of point mutations of the cardiac myosin head on the regulation of muscle contraction and could lead to better management by pharmacological approaches.

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Project description:Muscle architecture is an important component of muscle function, and recent studies have shown changes in muscle architecture with fatigue. The stretch-shortening cycle is a natural way to study human locomotion, but little is known about how muscle architecture is affected by this type of exercise. This study investigated potential changes in medial gastrocnemius (MG) muscle architecture after exhaustive stretch-shortening cycle exercise. Male athletes (n = 10) performed maximal voluntary contractions (MVC) and maximal drop jump (DJ) tests before and after an exercise task consisting of 100 maximal DJs followed by successive rebound jumping to 70% of the initial maximal height. The exercise task ceased upon failure to jump to 50% of maximal height or volitional fatigue. Muscle architecture of MG was measured using ultrasonography at rest and during MVC, and performance variables were calculated via a force plate and motion analysis. After SSC exercise, MVC (-13.1%; p = 0.005; dz = 1.30), rebound jump height (-14.8%, p = 0.004; dz = 1.32), and ankle joint stiffness (-26.3%; p = 0.008; dz = 1.30) decreased. Ankle joint range of motion (+20.2%; p = 0.011; dz = 1.09) and MG muscle-tendon unit length (+12.0%; p = 0.037; dz = 0.91) during the braking phase of DJ, the immediate drop-off in impact force (termed peak force reduction) (?27.3%; p = 0.033; dz = 0.86), and lactate (+9.5 mmol/L; p < 0.001; dz = 3.58) increased. Fascicle length increased at rest (+4.9%; p = 0.013; dz = 1.16) and during MVC (+6.8%; p = 0.048; dz = 0.85). Pennation angle decreased at rest (-6.5%; p = 0.034, dz = 0.93) and during MVC (-9.8%; p = 0.012; dz = 1.35). No changes in muscle thickness were found at rest (-2.6%; p = 0.066; dz = 0.77) or during MVC (-1.6%; p = 0.204; dz = 0.49). The greater MG muscle-tendon stretch during the DJ braking phase after exercise indicates that muscle damage likely occurred. The lower peak force reduction and ankle joint stiffness, indicative of decreased active stiffness, suggests activation was likely reduced, causing fascicles to shorten less during MVC.

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Cross-Bridges and Sarcomeric Non-cross-bridge Structures Contribute to Increased Work in Stretch-Shortening Cycles.

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