Dataset Information

Non-cross Bridge Viscoelastic Elements Contribute to Muscle Force and Work During Stretch-Shortening Cycles: Evidence From Whole Muscles and Permeabilized Fibers.

ABSTRACT: 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.

SUBMITTER: Hessel AL

PROVIDER: S-EPMC8039322 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description: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.

Project description:Chromosomal rearrangements are a major driver of eukaryotic genome evolution, affecting speciation, pathogenicity and cancer progression. Changes in chromosome structure are often initiated by mis-repair of double-strand breaks in the DNA. Mis-repair is particularly likely when telomeres are lost or when dispersed repeats misalign during crossing-over. Fungi carry highly polymorphic chromosomal complements showing substantial variation in chromosome length and number. The mechanisms driving chromosome polymorphism in fungi are poorly understood. We aimed to identify mechanisms of chromosomal rearrangements in the fungal wheat pathogen Zymoseptoria tritici. We combined population genomic resequencing and chromosomal segment PCR assays with electrophoretic karyotyping and resequencing of parents and offspring from experimental crosses to show that this pathogen harbors a highly diverse complement of accessory chromosomes that exhibits strong global geographic differentiation in numbers and lengths of chromosomes. Homologous chromosomes carried highly differentiated gene contents due to numerous insertions and deletions. The largest accessory chromosome recently doubled in length through insertions totaling 380 kb. Based on comparative genomics, we identified the precise breakpoint locations of these insertions. Nondisjunction during meiosis led to chromosome losses in progeny of three different crosses. We showed that a new accessory chromosome emerged in two viable offspring through a fusion between sister chromatids. Such chromosome fusion is likely to initiate a breakage-fusion-bridge (BFB) cycle that can rapidly degenerate chromosomal structure. We suggest that the accessory chromosomes of Z. tritici originated mainly from ancient core chromosomes through a degeneration process that included BFB cycles, nondisjunction and mutational decay of duplicated sequences. The rapidly evolving accessory chromosome complement may serve as a cradle for adaptive evolution in this and other fungal pathogens.

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.

Project description:Disinhibition of reflexes is a problem amongst spastic patients, for it limits a smooth and efficient execution of motor functions during gait. Treadmill belt accelerations may potentially be used to measure reflexes during walking, i.e. by dorsal flexing the ankle and stretching the calf muscles, while decelerations show the modulation of reflexes during a reduction of sensory feedback. The aim of the current study was to examine if belt accelerations and decelerations of different intensities applied during the stance phase of treadmill walking can evoke reflexes in the gastrocnemius, soleus and tibialis anterior in healthy subjects. Muscle electromyography and joint kinematics were measured in 10 subjects. To determine whether stretch reflexes occurred, we assessed modelled musculo-tendon length and stretch velocity, the amount of muscle activity, as well as the incidence of bursts or depressions in muscle activity with their time delays, and co-contraction between agonist and antagonist muscle. Although the effect on the ankle angle was small with 2.8±1.0°, the perturbations caused clear changes in muscle length and stretch velocity relative to unperturbed walking. Stretched muscles showed an increasing incidence of bursts in muscle activity, which occurred after a reasonable electrophysiological time delay (163-191 ms). Their amplitude was related to the muscle stretch velocity and not related to co-contraction of the antagonist muscle. These effects increased with perturbation intensity. Shortened muscles showed opposite effects, with a depression in muscle activity of the calf muscles. The perturbations only slightly affected the spatio-temporal parameters, indicating that normal walking was retained. Thus, our findings showed that treadmill perturbations can evoke reflexes in the calf muscles and tibialis anterior. This comprehensive study could form the basis for clinical implementation of treadmill perturbations to functionally measure reflexes during treadmill-based clinical gait analysis.

Dataset Information

Non-cross Bridge Viscoelastic Elements Contribute to Muscle Force and Work During Stretch-Shortening Cycles: Evidence From Whole Muscles and Permeabilized Fibers.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets