Cross bridge slippage induced by the ATP analogue AMP-PNP and stretch in glycerol-extracted fibrillar muscle fibres

Glycerol-extracted insect fibrillar muscle fibres in rigor exhibited both an elastic and a plastic phase in the length-tension diagram. The transition between these phases took place at a critical tension, the yield point or elastic limit. In the plastic phase the apparent static elastic modulus became zero, whereas the immediate elastic modulus (measured by rapid length changes completed within 4 ms) exhibited no abrupt change at the yield point. The tension value of the yield point (but not immediate stiffness) was lowered by addition of AMP-PNP and was partially restored by washing out AMP-PNP. The dependence of the critical tension at which plastic flow begins on cooperative cross bridge behaviour is discussed in terms of breaking and reforming acto-myosin linkages. Evidence is presented that addition of AMP-PNP induces slippage of cross bridges on the actin filament by affecting the interaction between myosin and actin.     

Tension transients in fibrillar muscle fibres as affected by stretch-dependent binding of AMP-PNP: A teinochemical effect?

The recovery in tension after release of a fibrillar muscle preparation as well as the fall in tension after restretch was found to be greater in presence of AMP-PNP than in its absence (rigor). The effect of AMP-PNP was concentration-dependent with an optimum at 0.1 mM corresponding to the dissociation constant of AMP-PNP from the myosin heads. This evidence supports the validity of the teinochemical principle which predicts a stretch-dependent AMP-PNP binding. The stiffness calculated per cross bridge was similar to that found by Huxley and Simmons (1971). It was further calculated that only 15% of the cross bridges are in a force-maintaining state in rigor.     

Fading memory model for airway smooth muscle dynamic response

This work presents the application of a fading memory model to describe the behavior of contracted airway smooth muscle (ASM) for two biophysical cases: finite duration length steps and longitudinal sinusoidal oscillations. The model parameters were initially determined from literature data on transient step length change response and subsequently the model was applied to the two cases. Results were compared with previously published experimental data on ASM oscillations. The model confirms a trend observed in the experimental data which shows that: (i) the value of tissue length change is the most important factor to determine the degree of cross-bridge detachment and (ii) a strong correlation exists between increasing frequency and declining stiffness until a certain frequency (∼25 Hz) beyond which frequency dependence is negligible. Although the model was not intended to simulate biophysical events individually, the data could be explained by cross-bridge cycling rates. As the frequency increases, cross-bridge reattachment becomes less likely, until no further cross-bridge attachment is possible.     

Stiffness and tension during and after sudden length changes of glycerinated rabbit psoas muscle fibres

A sudden stretch (within 0.3 ms) of glycerol-extracted rabbit psoas fibre bundle suspended in ATP-salt solution caused an immediate tension increase followed by a rapid tension decay (quick phase) which was nearly completed within 3 ms. The quick phase was missing or much reduced in the absence of ATP when the fibres were in rigor. Since the immediate stiffness of the fibres was nearly the same at the onset and at the end of the quick phase, the latter cannot be due to cross-bridges detachment per se. However, it may be ascribed to a conformational change (e.g. rotation) of attached bridges as suggested by Huxley and Simmons. Alternatively it might be explained by a slippage of attached cross-bridges. This mechanism would presuppose fast detachment and reattachment of strongly strained cross-bridges during the quick phase. Evidence for such a process was obtained by analysing the tension transients obtained when fibre bundles subjected to a large stretch were subsequently (within 10 ms) released to the initial length, as well as from stiffness measurements during the sudden length change: The stiffness was not found to be constant either during stretch or during the release. This may be taken to mean that the number of attached cross-bridges does not remain constant even during a rapid length change. In view of these results, the model proposed by Huxley and Simmons might be extended to take account of rapid attachment and detachment of crossbridges.     

Cross-bridge cycling theories cannot explain high-speed lengthening behavior in frog muscle.

The Huxley 1957 model of cross-bridge cycling accounts for the shortening force-velocity curve of striated muscle with great precision. For forced lengthening, however, the model diverges from experimental results. This paper examines whether it is possible to bring the model into better agreement with experiments, and if so what must be assumed about the mechanical capabilities of cross-bridges. Of particular interest is how introduction of a maximum allowable cross-bridge strain, as has been suggested by some experiments, affects the predictions of the model. Because some differences in the models are apparent only at high stretch velocities, we acquired new force-velocity data to permit a comparison with experiment. Using whole, isolated frog sartorius muscles at 2 degrees C, we stretched active muscle at speeds up to and exceeding 2 Vmax. Force during stretch was always greater than the peak isometric level, even during the fastest stretches, and was approximately independent of velocity for stretches faster than 0.5 Vmax. Although certain modifications to the model brought it into closer correspondence with the experiments, the accompanying requirements on cross-bridge extensibility were unreasonable. We suggest (both in this paper and the one that follows) that sarcomere inhomogeneities, which have been implicated in such phenomena as "tension creep" and "permanent extra tension," may also play an important role in determining the basic force-velocity characteristics of muscle.     

Cross-bridge mechanism of residual force enhancement after stretching in a skeletal muscle

A muscle model that uses a modified Langevin equation with actomyosin potentials was used to describe the residual force enhancement after active stretching. Considering that the new model uses cross-bridge theory to describe the residual force enhancement, it is different from other models that use passive stretching elements. Residual force enhancement was simulated using a half sarcomere comprising 100 myosin molecules. In this paper, impulse is defined as the integral of an excess force from the steady isometric force over the time interval for which a stretch is applied. The impulse was calculated from the force response due to fast and slow muscle stretches to demonstrate the viscoelastic property of the cross-bridges. A cross-bridge mechanism was proposed as a way to describe the residual force enhancement on the basis of the impulse results with reference to the compliance of the actin filament. It was assumed that the period of the actin potential increased by 0.5% and the amplitude of the potential decreased by 0.5% when the half sarcomere was stretched by 10%. The residual force enhancement after 21.0% sarcomere stretching was 6.9% of the maximum isometric force of the muscle; this value was due to the increase in the number of cross-bridges.     

Considerations on muscle contraction

The independent force generator and the power-stroke cross-bridge model have dominated the thinking on mechanisms of muscular contraction for nearly the past five decades. Here, we review the evolution of the cross-bridge theory from its origins as a two-state model to the current thinking of a multi-state mechanical model that is tightly coupled with the hydrolysis of ATP. Finally, we emphasize the role of skeletal muscle myosin II as a molecular motor whose actions are greatly influenced by Brownian motion. We briefly consider the conceptual idea of myosin II working as a ratchet rather than a power stroke model, an idea that is explored in detail in the companion paper.     

Sensitivity of muscle and intervertebral disc force computations to variations in muscle attachment sites

Abstract

The current paper aims at assessing the sensitivity of muscle and intervertebral disc force computations against potential errors in modeling muscle attachment sites. We perturbed each attachment location in a complete and coherent musculoskeletal model of the human spine and quantified the changes in muscle and disc forces during standing upright, flexion, lateral bending, and axial rotation of the trunk. Although the majority of the muscles caused minor changes (less than 5%) in the disc forces, certain muscle groups, for example, quadratus lumborum, altered the shear and compressive forces as high as 353% and 17%, respectively. Furthermore, percent changes were higher in the shear forces than in the compressive forces. Our analyses identified certain muscles in the rib cage (intercostales interni and intercostales externi) and lumbar spine (quadratus lumborum and longissimus thoracis) as being more influential for computing muscle and disc forces. Furthermore, the disc forces at the L4/L5 joint were the most sensitive against muscle attachment sites, followed by T6/T7 and T12/L1 joints. Presented findings suggest that modeling muscle attachment sites based on solely anatomical illustrations might lead to erroneous evaluation of internal forces and promote using anatomical datasets where these locations were accurately measured. When developing a personalized model of the spine, certain care should also be paid especially for the muscles indicated in this work.     

Reduced stretch reflex sensitivity and muscle stiffness after long-lasting stretch-shortening cycle exercise in humans

It has been suggested that during repeated long-term stretch-shortening cycle (SSC) exercise the decreased neuromuscular function may result partly from alterations in stiffness regulation. Therefore, interaction between the short latency stretch-reflex component (M₁) and muscle stiffness and their influences on muscle performance were investigated before and after long lasting SSC exercise. The test protocol included various jumps on a sledge ergometer. The interpretation of the sensitivity of the reflex was based on the measurements of the patellar reflexes and the M₁ reflex components. The peak muscle stiffness was measured indirectly and calculated as a coefficient of the changes in the Achilles tendon force and the muscle length. The fatigue protocol induced a marked impairment of the neuromuscular function in maximal SSC jumps. This was demonstrated by a 14.1%–17.7% (n.s. –P < 0.001) reduction in the mean eccentric forces and a 17.3%–31.8% (n.s. –P < 0.05) reduction in the corresponding M₁ area under the electromyograms. Both of these methods of assessing the short latency reflex response showed a clear deterioration in the sensitivity of the reflex after fatigue (P < 0.05–0.001). This was also the case for the eccentric peak stiffness of the soleus muscle which declined immediately after fatigue by 5.4% to 7.1% (n.s. –P < 0.05) depending on the jump condition. The results observed would suggest that the modulation of neural input to the muscle was at least partly of reflex origin from the contracting muscle, and furthermore, that the reduced muscle stiffness which accompanied the decreased reflex sensitivity could have been partly responsible for the weakened muscle performance due to impaired utilization of elastic energy. Accepted: 28 April 1998     

Effect of static stretching with different rest intervals on muscle stiffness

The aim of the study was to investigate the effect of static stretching (SS) with different rest intervals on muscle stiffness. Fifteen healthy males participated in the study. Four bouts of thirty-second SS for the gastrocnemii were performed at the maximal dorsiflexion using dynamometer with two different rest intervals between stretches, namely 0 s (R0) and 30 s (R30). Each participant underwent both stretching protocols at least 48 h apart in a random order. Between each bout of SS, the ankle was moved to 20°-plantar-flexion in 3 s, held for each rest interval time, and then returned to the stretching position in 3 s. The shear elastic modulus of the medial gastrocnemius was measured before (PRE) and immediately after (POST) four bouts of SS to assess muscle stiffness of the medial gastrocnemius. Two-way repeated measures analysis of variance (protocol × time) indicated a significant interaction effect on the shear elastic modulus. The shear elastic modulus significantly decreased after SS in both protocols [R0, PRE: 11.5 ± 3.3 kPa, POST: 10.0 ± 2.6 kPa, amount of change: 1.6 ± 0.9 kPa (13.0 ± 5.2%); R30, PRE: 11.0 ± 2.8 kPa, POST: 10.2 ± 2.1 kPa, amount of change: 0.8 ± 1.3 kPa (6.0 ± 10.4%)]. Furthermore, the SS with 0-s rest interval induced greater decrease in shear elastic modulus when compared to SS with 30-s rest interval (p = 0.023). Thus, when performing SS to decrease muscle stiffness, rest intervals between stretches should be minimized.     

The innervation of a ventral abdominal protractor muscle in Locusta

The innervation of the external ventral protractor muscle of the VIIth abdominal segment (M234) of Locusta migratoria is described using a combination of neurophysiological and neuroanatomical techniques. Cobalt backfills of the nerve innervating M234 revealed two neurons each with soma and fields of arborization in the VIIth abdominal ganglion. In addition, extracellular stimulation of the nerve while gradually increasing the stimulus amplitude resulted in a stepwise increase in both the excitatory junction potential amplitude and twitch amplitude so that two different amplitudes of each were observed indicating the sequential recruitment of two motor neurons. 4-Di-2-ASP stains of M234 revealed pre-synaptic boutons at M234 and a neurohaemal plexus covering the nerve the latter being corroborated by electron microscopic examination of nerve sections. Electron microscopic examination of M234 revealed two axon terminal types, one which is similar to the neurohaemal varicosities over the nerve, containing granules of high electron-density, and one which contains larger granules of medium electron-density. Both terminals types also contained small electron lucent vesicles. Finally, twitch contractions of M234 were modulated by glutamate, proctolin, octopamine, and SchistoF-LRFamide.Abbreviations EGAA Enhanced Graphics Acquisition and Analysis system by RC-Electronics, California - EJP excitatory junction potential - OA octopamine     

Formation of muscle spindles in regenerated avian muscle grafts

Summary Pigeon muscles lacking muscle spindles were grafted into sites which normally have a muscle containing spindles. The reciprocal transplantations were also made. After two to eight months, the graft of the donor muscle without spindles had regenerated into a muscle containing muscle spindles. The reciprocal grafts, muscles containing spindles transplanted to a site lacking spindle innervation, had neither muscle spindles nor remnants of the spindles. These experiments demonstrate that 1) the innervation is required for formation of the spindle; 2) the original spindles do not survive transplantation; and 3) parts of the original spindle are not required for spindle regeneration.This work was supported in part by NSF grants PCM 77-15960 and PCM 79-16540     

Motor control of the mandible closer muscle in ants

Despite their simple design, ant mandible movements cover a wide range of forces, velocities and amplitudes. The mandible is controlled by the mandible closer muscle, which is composed of two functionally distinct subpopulations of muscle fiber types: fast fibers (short sarcomeres) and slow ones (long sarcomeres). The entire muscle is controlled by 10-12 motor neurons, 4-5 of which exclusively supply fast muscle fibers. Slow muscle fibers comprise a posterior and an antero-lateral group, each of which is controlled by 1-2 motor neurons. In addition, 3-4 motor neurons control all muscle fibers together. Simultaneous recordings of muscle activity and mandible movement reveal that fast movements require rapid contractions of fast muscle fibers. Slow and subtle movements result from the activation of slow muscle fibers. Forceful movements are generated by simultaneous co-activation of all muscle fiber types. Retrograde tracing shows that most dendritic arborizations of the different sets of motor neurons share the same neuropil in the subesophageal ganglion. In addition, fast motor neurons and neurons supplying the lateral group of slow closer muscle fibers each invade specific parts of the neuropil that is not shared by the other motor neuron groups. Some bilateral overlap between the dendrites of left and right motor neurons exists, particularly in fast motor neurons. The results explain how a single muscle is able to control the different movement parameters required for the proper function of ant mandibles.     

Orientation of the backbone structure of myosin filaments in relaxed and rigor muscles of the housefly: Evidence for non-equivalent crossbridge positions at the surface of thick filaments

The orientation of the backbone structure of myosin filaments of relaxed and rigor fibers of the flight muscles of the housefly, Musca domestica, relative to the actin filaments has been investigated. In relaxed muscles 23% of the myosin filaments have gaps in the wall of their shaft located opposite the surrounding actin filaments, while in 77% the subfilament pairs of the wall are thus located. These are the expected values if the backbone orientation is random. In rigor muscles 40% of the thick filaments have their gaps opposite the actins and 60%, the subfilament pairs are opposite the actins. This increase in the percentage of filaments with gaps opposite the actins therefore results from binding of the crossbridges in rigor with change in rotational orientation of the backbone. The findings are related to a model of Beinbrech et al. (1988) in which two populations of crossbridges have been postulated: one originating at the surface of the thick filaments, the other coming from within the gap between the subfilament pairs.     

Proteomics of skeletal muscle glycolysis

Glycolysis represents one of the best-understood and most ancient metabolic pathways. In skeletal muscle fibres, energy for contraction is supplied by adenosine triphosphate via anaerobic glycolysis, the phosphocreatine shuttle and oxidative phosphorylation. In this respect, the anaerobic glycolytic pathway supports short duration performances of contractile tissues of high intensity. The catalytic elements associated with glycolysis are altered during development, muscle differentiation, physiological adaptations and many pathological mechanisms, such as muscular dystrophy, diabetes mellitus and age-related muscle weakness. Although gel electrophoresis-based proteomics is afflicted with various biological and technical problems, it is an ideal analytical tool for studying the abundant and mostly soluble enzymes that constitute the glycolytic system. This review critically examines the proteomic findings of recent large-scale studies of glycolytic enzymes and associated components in normal, transforming and degenerating muscle tissues. In the long term, proteins belonging to the glycolytic pathway may be useful as biomarkers of muscle adaptations and pathophysiological mechanisms and can be employed to improve diagnostics and in the identification of novel therapeutic targets in neuromuscular disorders.     

Functional analysis of limb recovery following autograft treatment of volumetric muscle loss in the quadriceps femoris

Severe injuries to the extremities often result in muscle trauma and, in some cases, significant volumetric muscle loss (VML). These injuries continue to be challenging to treat, with few available clinical options, a high rate of complications, and often persistent loss of limb function. To facilitate the testing of regenerative strategies for skeletal muscle, we developed a novel quadriceps VML model in the rat, specifically addressing functional recovery of the limb. Our outcome measures included muscle contractility measurements to assess muscle function and gait analysis for evaluation of overall limb function. We also investigated treatment with muscle autografts, whole or minced, to promote regeneration of the defect area. Our defect model resulted in a loss of muscle function, with injured legs generating less than 55% of muscle strength from the contralateral uninjured control legs, even at 4 weeks post-injury. The autograft treatments did not result in significant recovery of muscle function. Measures of static and dynamic gait were significantly decreased in the untreated, empty defect group, indicating a decrease in limb function. Histological sections of the affected muscles showed extensive fibrosis, suggesting that this scarring of the muscle may be in part the cause of the loss of muscle function in this VML model. Taken together, these data are consistent with clinical findings of reduced muscle function in large VML injuries. This new model with quantitative functional outcome measures offers a platform on which to evaluate treatment strategies designed to regenerate muscle tissue volume and restore limb function.     

失重状态下肌萎缩研究进展

失重条件下人和动物生理状态会发生一系列的变化,其中骨骼肌萎缩和力量下降较为显著,目前其发生的机制仍不明确且缺少特效的干预措施。本文从肌肉湿重及肌纤维横截面积的变化、肌纤维类型的变化、肌纤维超微结构的变化、肌梭的适应性变化四个方面进行简要阐述,探讨肌肉萎缩的可能发生机制。     

A mechanism accounting for independence on starting length of tension increase in ramp stretches of active skeletal muscle at short half-sarcomere lengths

Based on previous experimental results of independence on starting length of the tension gradient in constant-velocity stretches of active skeletal muscle at muscle lengths including the ascending limb and the plateau of the tension-length relation, a possible physiological mechanism determining the tension increase in lengthening active muscle is discussed. Considering the sliding filament theory, it is suggested that the tension-length relation of a half-sarcomere in lengthening contractions is different from that in isometric contractions. The assumed mechanism predicts, among others, that the thick filament retains its shortened length in lengthening contractions starting from a half-sarcomere length where this filament is compressed. An example model is implemented and checked with simulations.