Reactive oxygen species and redox-regulation of skeletal muscle adaptations to exercise

Skeletal muscle has been shown to generate a complex set of reactive oxygen and nitrogen species (ROS) both at rest and during contractile activity. The primary ROS generated are superoxide and nitric oxide and the pattern and magnitude of their generation is influenced by the nature of the contractile activity. It is increasingly clear that the ROS generated by skeletal muscle play an important role in influencing redox-regulated processes that control, at least some of, the adaptive responses to contractile activity. These processes are also recognized to be modified during ageing and in some disease states, providing the potential that interventions affecting ROS activity may influence muscle function or viability in these situations.     

Use of motor cortex stimulation to measure simultaneously the changes in dynamic muscle properties and voluntary activation in human muscles.

Force responses to transcranial magnetic stimulation of motor cortex (TMS) during exercise provide information about voluntary activation and contractile properties of the muscle. Here, TMS-generated twitches and muscle relaxation during the TMS-evoked silent period were measured in fresh, heated, and fatigued muscle. Subjects performed isometric contractions of elbow flexors in two studies. Torque and EMG were recorded from elbow flexor and extensor muscles. One study (n = 6) measured muscle contraction times and relaxation rates during brief maximal and submaximal contractions in fresh and fatigued muscle. Another study (n = 7) aimed to 1) assess the reproducibility of muscle contractile properties during brief voluntary contractions in fresh muscle, 2) validate the technique for contractile properties in passively heated muscle, and 3) apply the technique to study contractile properties during sustained maximal voluntary contractions. In both studies, muscle contractile properties during voluntary contractions were compared with the resting twitch evoked by motor nerve stimulation. Measurement of muscle contractile properties during voluntary contractions is reproducible in fresh muscle and reveals faster and slower muscle relaxation rates in heated and fatigued muscle, respectively. The technique is more sensitive to altered muscle state than the traditional motor nerve resting twitch. Use of TMS during sustained maximal contractions reveals slowing of muscle contraction and relaxation with different time courses and a decline in voluntary activation. Voluntary output from the motor cortex becomes insufficient to maintain complete activation of muscle, although slowing of muscle contraction and relaxation indicates that lower motor unit firing rates are required for fusion of force.     

Proteomic profiling of chronic low-frequency stimulated fast muscle

Skeletal muscle fibre transitions occur in many biological processes, in response to alterations in neuromuscular activity, in muscular disorders, during age-induced muscle wasting and in myogenesis. It was therefore of interest to perform a comprehensive proteomic profiling of muscle transformation. Chronic low-frequency stimulation of the rabbit tibialis anterior muscle represents an established model system for studying the response of fast fibres to enhanced neuromuscular activity under conditions of maximum activation. We have conducted a DIGE analysis of unstimulated control specimens versus 14- and 60-day conditioned muscles. A differential expression pattern was observed for 41 protein species with 29 increased and 12 decreased muscle proteins. Identified classes of proteins that are changed during the fast-to-slow transition process belong to the contractile machinery, ion homeostasis, excitation-contraction coupling, capillarization, metabolism and stress response. Results from immunoblotting agreed with the conversion of the metabolic, regulatory and contractile molecular apparatus to support muscle fibres with slower twitch characteristics. Besides confirming established muscle elements as reliable transition markers, this proteomics-based study has established the actin-binding protein cofilin-2 and the endothelial marker transgelin as novel biomarkers for evaluating muscle transformation.     

An investigation of arterial insufficiency in the rat hindlimb. Correlation of skeletal muscle bloodflow and glucose utilization in vivo.

Muscle bloodflow and the rate of glucose uptake and phosphorylation were measured in vivo in rats 7 days after unilateral femoral artery ligation and section. Bloodflow was determined by using radiolabelled microspheres. At rest, bloodflow to the gastrocnemius, plantaris and soleus muscles of the ligated limb was similar to their respective mean contralateral control values; however, bilateral sciatic nerve stimulation at 1 Hz caused a less pronounced hyperaemic response in the muscles of the ligated limb, being 59, 63 and 49% of their mean control values in the gastrocnemius, plantaris and soleus muscles respectively. The rate of glucose utilization was determined by using the 2-deoxy[3H]glucose method [Ferré, Leturque, Burnol, Penicaud & Girard (1985) Biochem. J. 228, 103-110]. At rest, the rate of glucose uptake and phosphorylation was statistically significantly increased in the gastrocnemius and soleus muscles of the ligated limb, being 126 and 140% of the mean control values respectively. Bilateral sciatic nerve stimulation at 1 Hz caused a 3-5-fold increase in the rate of glucose utilization by the ligated and contralateral control limbs; furthermore, the rate of glucose utilization was significantly increased in the muscles of the ligated limb, being 140, 129 and 207% of their mean control values respectively. For the range of bloodflow to normally perfused skeletal muscle at rest or during isometric contraction determined in the present study, a linear correlation between the rate of glucose utilization and bloodflow can be demonstrated. Applying similar methods of regression analysis to glucose utilization and bloodflow to muscles of the ligated limb reveals a similar linear correlation. However, the rate of glucose utilization at a given bloodflow is increased in muscles of the ligated limb, indicating an adaptation of skeletal muscle to hypoperfusion.     

Kinetic analysis of contraction-relaxation process in smooth muscles

A method is proposed for analysing kinetic curves of the smooth muscle contraction--relaxation approved on smooth muscle preparations of ureter and taenia coli. A notion of the velocity coefficient is introduced. It is the parameter which gives a quantitative characteristics of changes in the dynamics of muscle contraction and relaxation under the effect of factors modifying the contractile response. In order to illustrate the application of this parameter studies were carried out of the effect of sodium-free medium, monensin, and of temperature decrease on the contractile activity of the smooth muscle tissue of the ureter. The method can be useful while investigating the regularities of electro- and pharmacomechanical conjunction in the smooth muscles, as well as during pharmacological screening of compounds--regulators of calcium homeostasis in myocytes and their contractile activity.     

ADRENALIN IN ANNELIDS : A CONTRIBUTION TO THE COMPARATIVE STUDY OF THE ORIGIN OF THE SYMPATHETIC AND THE ADRENALIN-SECRETING SYSTEMS AND OF THE VASCULAR MUSCLES WHICH THEY REGULATE.

1. The sympathetic nervous system and the adjuvant adrenalin-secreting system are found in their earliest form in the annelid kingdom, and consist of cells situated in the central nervous system which are the common ancestors of both, and which are both secretory and nervous in function. 2. These cells are developed in the annelid kingdom parallel with the development of a contractile vascular system, which possesses muscles comparable in physiological actions with the muscle of the vertebrate heart. 3. This vascular muscle is regulated by the processes of the common ancestral cells as well as by their secretory activity. 4. In the primitive form contractile rhythm is an intrinsic property of cardiac muscle; its nerve supply regulates the rhythm, it does not initiate it. The beat is therefore myogenic, not neurogenic. 5. The contractile vascular system of annelids is mainly branchial in function. The vertebrate heart has been derived from it by the growing around of the lateral body folds to form a new ventral surface.     

Development of the muscle system and contractile activity in the mussel Mytilus trossulus (Mollusca, Bivalvia)

The development of contractile apparatus was subjected to comparative analysis during ontogenesis of the mussel Mytilus trossulus. Indirect immunofluorescence with the polyclonal antibody against mussel twitchin, a protein of thick filaments, and florescent phalloidin as a marker of filamentous cell actin were used to monitor changes in the developing muscle system at different larval stages. The first definitive muscle structures were found at the late trochophore stage (36 h after fertilization) and starting from the midveliger stage (96 h), striated muscles, which are never present in adult mussels, were distinctly seen. The striated muscle periodicity was 1.25 microm in both mussle larvae and adult scallop. The contractile activities of veliger and adult muscles were measured using an electronic signal-processing videosystem. This work is the first complex study of morphological, biochemical, and physiological characteristics of the muscle system in the larvae and adult mollusks.     

Free radicals generated by contracting muscle: by-products of metabolism or key regulators of muscle function?

Skeletal muscle fibers generate reactive oxygen species (ROS) at a number of subcellular sites and this generation is increased by contractile activity. Early studies suggested that generation of superoxide as a by-product of mitochondrial oxygen consumption was the major source of muscle ROS generation and that the species produced were inevitably damaging to muscle, but recent data argue against both of these possibilities. Developments in analytical approaches have shown that specific ROS are generated in a controlled manner by skeletal muscle fibers in response to physiological stimuli and play important roles in the physiological adaptations of muscle to contractions. These include optimization of contractile performance and initiation of key adaptive changes in gene expression to the stresses of contractions. These positive benefits of the ROS that are induced by contractile activity contrast starkly with the increasing evidence that ROS-induced degenerative pathways are fundamental to aging processes in skeletal muscle. A fuller understanding of these contrasting roles is recognized to be important in the design of strategies to maintain and optimize skeletal muscle function during exercise and to help prevent the devastating effects of sarcopenia and other muscle-wasting conditions.     

Repiratory muscle dysfunction in sepsis

It became evident in the past 12 years that venitlatory muscle contractile performance is significantly impaired during the course of septic shock. In animal models of septic shock, depression of ventilatory muscle contractile performance has been shown to cause hypercapneic ventilatory failure and respiratory arrest. Failure of ventilatory muscle contractility in septic shock has never been attributed to a single factor, but two groups of factors are likely to be involved: (a) increased ventilatory muscle metabolic demands due to augmentation of ventilation, hypoxemia and increased pulmonary impedance; and (b) specific cellular, metabolic, immune and hemodynamic defects which interfere with several processes necessary for normal force generation. These defects are mediated by complex interactions between several local and systematic mediator such a bacterial endotoxin, proinflammatory cytokines, prostaglandins, platelet activating factor, reactive oxygen species and nitric oxide. This is a summary of how these interactions are likely to interfere with ventilatory muscle contractile performance in septic shock with particular emphasis on the newly described role of nitric oxide.     

Development of the muscle system and contractile activity in the mussel <Emphasis Type="Italic">Mytilus trossulus</Emphasis> (Mollusca,Bivalvia)

The development of contractile apparatus was subjected to comparative analysis during ontogenesis of the mussel Mytilus trossulus. Indirect immunofluorescence with the polyclonal antibody against mussel twitchin, a protein of thick filaments, and fluorescent phalloidin as a marker of filamentous cell actin were used to monitor changes in the developing muscle system at different larval stages. The first definitive muscle structures were found at the late trochophore stage (36 h after fertilization) and starting from the midveliger stage (96h), striated muscles, which are never present in adult mussels, were distinctly seen. The striated muscle periodicity was 1.25 μm in both mussel larvae and adult scallop. The contractile activities of veliger and adult muscles were measured using an electronic signal-processing video workstation. This work is the first complex study of morphological, biochemical, and physiological characteristics of the muscle system in the larvae and adult molluscs.     

Myosin heavy chain and parvalbumin expression in swimming and feeding muscles of centrarchid fishes: the molecular basis of the scaling of contractile properties

In centrarchid fishes, such as bluegill (Lepomis macrochirus, Rafinesque) and largemouth bass (Micropterus salmoides, Lacepède), the contractile properties of feeding and swimming muscles show different scaling patterns. While the maximum shortening velocity (V(max)) and rate of relaxation from tetanus of swimming or myotomal muscle slow with growth, the feeding muscle shows distinctive scaling patterns. Cranial epaxial muscle, which is used to elevate the head during feeding strikes, retains fast contractile properties across a range of fish sizes in both species. In bass, the sternohyoideous muscle, which depresses the floor of the mouth during feeding strikes, shows faster contractile properties with growth. The objective of this study was to determine the molecular basis of these different scaling patterns. We examined the expression of two muscle proteins, myosin heavy chain (MyHC) and parvalbumin (PV), that affect contractile properties. We hypothesized that the relative contribution of slow and fast MyHC isoforms will modulate V(max) in these fishes, while the presence of PV in muscle will enhance rates of muscle relaxation. Myotomal muscle displays an increase in sMyHC expression with growth, in agreement with its physiological properties. Feeding muscles such as epaxial and sternohyoideus show no change or a decrease in sMyHC expression with growth, again as predicted from contractile properties. PV expression in myotomal muscle decreases with growth in both species, as has been seen in other fishes. The feeding muscles again show no change or an increase in PV expression with growth, contributing to faster contractile properties in these fishes. Both MyHC and PV appear to play important roles in modulating muscle contractile properties of swimming and feeding muscles in centrarchid fishes.     

Computational simulation of human upper airway collapse using a pressure-/state-dependent model of genioglossal muscle contraction under laminar flow conditions.

A three-element, pressure- and state (sleep and wake) -dependent contraction model of the genioglossal muscle was developed based on the microstructure of skeletal muscle and the cross-bridge theory. This model establishes a direct connection between the contractile forces generated in muscle fibers and the measured electromyogram signals during various upper airway conditions. This effectively avoids the difficulty of determining muscle shortening velocity during complex pharyngeal conditions when modeling the muscle's contractile behaviors. The activation of the genioglossal muscle under different conditions was then simulated. A sensitivity analysis was performed to determine the effects of varying each modeled parameter on the muscle's contractile behaviors. This muscle contraction model was then incorporated into our anatomically correct, two-dimensional computational model of the pharyngeal airway to perform a finite-element analysis of air flow, tissue deformation, and airway collapse. The model-predicted muscle deformations are consistent with previous observations regarding upper airway behavior in normal subjects.     

State of the contractile apparatus during the development of a pathological process in the muscles. II. The effect of Ca2+ on the morphology of spreading necrosis caused by UV light]

Using phase-contrast technique and electron microscopy, a study was made of morphological changes of contractile system of striated muscle fibre during the spreading necrosis caused by ultraviolet light damage. It has been shown that the degree of manifestation of destructive changes in the contractile system depends upon Ca2+-ion concentration. The ultrastructural study of the damage region, under condition of muscle fibre stretching, made it possible to reveal the initial stages of formation of this pathological process. A possible contribution of intracellular membranous structures in spreading the destructive process along the muscle fibre is discussed.     

The first three minutes: smooth muscle contraction, cytoskeletal events, and soft glasses.

Smooth muscle exhibits biophysical characteristics and physiological behaviors that are not readily explained by present paradigms of cytoskeletal and cross-bridge mechanics. There is increasing evidence that contractile activation of the smooth muscle cell involves an array of cytoskeletal processes that extend beyond cross-bridge cycling and the sliding of thick and thin filaments. We review here the evidence suggesting that the biophysical and mechanical properties of the smooth muscle cell reflect the integrated interactions of an array of highly dynamic cytoskeletal processes that both react to and transform the dynamics of cross-bridge interactions over the course of the contraction cycle. The activation of the smooth muscle cell is proposed to trigger dynamic remodeling of the actin filament lattice within cellular microdomains in response to local mechanical and pharmacological events, enabling the cell to adapt to its external environment. As the contraction progresses, the cytoskeletal lattice stabilizes, solidifies, and forms a rigid structure well suited for transmission of tension generated by the interaction of myosin and actin. The integrated molecular transitions that occur within the contractile cycle are interpreted in the context of microscale agitation mechanisms and resulting remodeling events within the intracellular microenvironment. Such an interpretation suggests that the cytoskeleton may behave as a glassy substance whose mechanical function is governed by an effective temperature.     

Free radical induced respiratory muscle dysfunction

It is now recognized that respiratory muscle fatigue contributes to the development of respiratory failure in some patients with lung disease. This observation has prompted an examination into the mechanisms of development of muscle fatigue, with the understanding that an elucidation of these processes may lead to new therapeutic approaches to the treatment of these patients. A series of recent studies examining this issue have, moreover, discovered that oxygen-derived free radicals generated during strenuous contraction may modulate respiratory muscle contractile function and contribute to the development of muscle fatigue. The data supporting this concept include: (a) direct (e.g. EPR, ESR studies) and indirect (evidence of lipid peroxidation, protein carbonyl formation, glutathione oxidation) evidence that there is heightened free radical production in contracting muscle, (b) evidence that pharmacologic depletion of muscle antioxidant stores increases degree of muscle fatigue present after a period of exercise, and (c) evidence that administration of agents that act as free radical scavengers retard the development muscle fatigue. Free radicals may produce these changes in muscle force generating capacity by interacting with and altering the function of a number of intracellular-biophysical processes (i.e. sarcolemmal action potential propagation, sarcoplasmic reticulum calcium handling, mitochondrial function, contractile protein interactions).     

Selected contribution: plasticity of airway smooth muscle stiffness and extensibility: role of length-adaptive mechanisms.

Airway smooth muscle exhibits the property of length adaptation, which enables it to optimize its contractility to the mechanical conditions under which it is activated. Length adaptation has been proposed to result from a dynamic modulation of contractile and cytoskeletal filament organization, in which the cell structure adapts to changes in cell shape at different muscle lengths. Changes in filament organization would be predicted to alter muscle stiffness and extensibility. We analyzed the effects of tracheal muscle length at the time of contractile activation on the stiffness and extensibility of the muscle during subsequent stretch over a constant range of muscle lengths. Muscle strips were significantly stiffer and less extensible after contractile activation at a short length than after activation at a long length, consistent with the prediction of a shorter, thicker array of the cytoskeletal filaments at a short muscle length. Stretch beyond the length of contractile activation resulted in a persistent reduction in stiffness, suggesting a stretch-induced structural rearrangement. Our results support a model in which the filament organization of airway smooth muscle cells is plastic and can be acutely remodeled to adapt to the changes in the external physical environment.     

Cholinergic mechanisms of the hypothalamus medial preoptic area in control of thermoregulation and of wakefulness-sleep states in pigeons

The data obtained show that cholinergic mechanisms of the medial preoptic area of hypothalamus participate in control of wakefulness-sleep states and thermoregulation parameters in pigeons. Muscarinic and nicotinic cholinergic receptors are established to be involved in the wakefulness maintenance. The muscarinic cholinergic receptor activation of the medial preoptic area is accompanied by an elevation of the brain temperature, by development of peripheral vasoconstriction, and by an in increase in level of the muscle contractile activity. During the nicotinic cholinergic receptor activation of the area, a decrease in the brain temperature and an increase in level of the muscle contractile activity are found. A comparative analysis of experiments and early investigation suggests that during the cholinergic receptors activation changes in the brain temperature of pigeons depend on type of the cholinergic receptors but not on their localization in the preoptic area of hypothalamus.     

Plasticity in mammalian skeletal muscle.

While it has been recognized for many years that different limb muscles belonging to the same mammal may have markedly differing contractile characteristics, it is only comparatively recently that it has been demonstrated that these differences depend upon the motor innervation. By appropriately changing the peripheral nerve innervating a mammalian skeletal muscle, it is possible to change dramatically the contractile behaviour of the reinnervated muscle. The manner by which the motor innervation determines the nature of a muscle fibre's contractile machinery is not completely understood, but it appears that the number and pattern of motor nerve impulses reaching the muscle play an important role. The biochemical changes occurring within muscle fibres whose contractile properties have been modified by altered motor innervation include the synthesis of different contractile proteins.     

Changes in contractile properties and neuromuscular propagation evaluated by simultaneous mechanomyogram and electromyogram during experimentally induced hypothermia.

The present study examined, whether or not mechanomyogram (MMG) amplitude and frequency component could reflect the contractile properties of the triceps surae muscles, composed of relatively slow soleus (SOL) and fast medial gastrocnemius (MG), during experimentally induced hypothermia condition. In eight male subjects, lying in prone position, supramaximal single twitch and repetitive electrical stimulations at 10 Hz were applied at the intramuscular temperatures of control (34 degrees C), 15, 20, and 25 degrees C, respectively. The hypothermia induced substantial reduction in muscle contractile properties, e.g. prolonged twitch contraction and half relaxation times, resulted in a highly significant reduction in the fluctuation of force signal during the repetitive stimulations. These changes were almost mirrored by the similar and significant reductions in the MMG amplitude in both SOL and MG. Power spectrum analysis revealed that peak frequency components of MMG and fluctuation of force were almost matched with the applied stimulation frequencies, independent of the temperature condition. These results strongly suggest that MMG analysis could be employed to study muscle contractile properties varying across different physiological conditions.