Muscle Contractile Activity Research Articles

Role of RyR2 and SERCA2a in the Cardioprotective Effects of Vincanine and Pyrazoline Alkaloids

In the conducted studies, the effect of vincanine and pyrazoline indole alkaloids on cardiac muscle cell sarcoplasmic reticulum (SR) Ca2+-transport systems (RyR2 and SERCA2a) was investigated under normal and hypoxic conditions. The effect of vincanine and pyrazoline on ryanodine receptor (RyR2) was evaluated in the presence of ruthenium red and it was found that the role of RyR2 in the positive inotropic effect of these alkaloids is small. Also, in the presence of cyclopiazonic acid (IC50 = 5.6 µM), an inhibitor of sarcoplasmic reticulum Ca2+-ATPase (SERCA2a), the positive inotropic effect of vincanine and pyrazoline alkaloids was reduced. In general, the positive inotropic effects and cardioprotective properties of vincanine and pyrazoline alkaloids are mediated by modulation of SERCA2a function. HIGHLIGHTS Vincanine and pyrazoline indole alkaloids have a positive inotropic effect on the force of papillary muscle contraction of the rat heart. Vincanine and pyrazoline indole alkaloids have a cardioprotective effect and effectively eliminate the disturbances in the papillary muscle contractile activity of the rat heart caused by hypoxia. Vincanine and pyrazoline alkaloids effectively reverse hypoxia-induced SERCA2a dysfunction and normalize changes in rat cardiac papillary muscle contractile activity. GRAPHICAL ABSTRACT

Mature enteric neurons have the capacity to reinnervate the intestine with glial cells as their guide

Here, we establish that plasticity exists within the postnatal enteric nervous system by demonstrating the reinnervation potential of post-mitotic enteric neurons (ENs). Employing BAF53b-Cre mice for selective neuronal tracing, the reinnervation capabilities of mature postnatal ENs are shown across multiple model systems. Isolated ENs regenerate neurites invitro, with neurite complexity and direction influenced by contact with enteric glial cells (EGCs). Nerve fibers from transplanted ENs exclusively interface and travel along EGCs within the muscularis propria. Resident EGCs persist after Cre-dependent ablation of ENs and govern the architecture of the myenteric plexus for reinnervating ENs, as shown by nerve fiber projection tracing. Transplantation and optogenetic experiments invivo highlight the rapid reinnervation potential of post-mitotic neurons, leading to restored gut muscle contractile activity within 2weeks. These studies illustrate the structural and functional reinnervation capacity of post-mitotic ENs and the critical role of EGCs in guiding and patterning their trajectories.

Effect of orthodontic appliances on masticatory muscle activity

There is limited and conflicting evidence regarding the impact of orthodontic appliances on masticatory muscle activity (MMA), jaw function, and oral parafunctional behaviours. Investigations in this field frequently utilise surface electromyography (sEMG) to analyse changes in muscle contractile activity. Fixed orthodontics appliances have been associated with significant reductions in MMA post archwire activation. Conversely, elevations in masseter and digastric muscle activity have been reported in response to removable functional appliances. Research into the effect of clear aligner therapy (CAT) on MMA is still in its infancy with few studies published. There is a lack of agreement on whether MMA increases or diminishes in response to CAT though there is evidence this relationship may change over time due to muscle adaptation. The impact of CAT on temporomandibular disorder (TMD) symptoms is unclear, particularly how pre-existing risk factors for TMD may alter and individual's response.

3D Airway Epithelial-Fibroblast Biomimetic Microfluidic Platform to Unravel Engineered Nanoparticle-Induced Acute Stress Responses as Exposome Determinants.

Insights into how biological systems respond to high- and low-dose acute environmental stressors are a fundamental aspect of exposome research. However, studying the impact of low-level environmental exposure in conventional in vitro settings is challenging. This study employed a three-dimensional (3D) biomimetic microfluidic lung-on-chip (μLOC) platform and RNA-sequencing to examine the effects of two model anthropogenic engineered nanoparticles (NPs): zinc oxide nanoparticles (Nano-ZnO) and copier center nanoparticles (Nano-CCP). The airway epithelium exposed to these NPs exhibited dose-dependent increases in cytotoxicity and barrier dysregulation (dominance of the external exposome). Interestingly, even nontoxic and low-level exposure (10 μg/mL) of the epithelium compartment to Nano-ZnO triggered chemotaxis of lung fibroblasts toward the epithelium. An increase in α smooth muscle actin (α-SMA) expression and contractile activity was also observed in these cells, indicating a bystander-like adaptive response (dominance of internal exposome). Further bioinformatics and network analysis showed that a low-dose Nano-ZnO significantly induced a robust transcriptomic response and upregulated several hub genes associated with the development of lung fibrosis. We propose that Nano-ZnO, even at a no observable effect level (NOEL) dose according to conventional standards, can function as a potent nanostressor to disrupt airway epithelium homeostasis. This leads to a cascade of profibrotic events in a cross-tissue compartment fashion. Our findings offer new insights into the early acute events of respiratory harm associated with environmental NPs exposure, paving the way for better exposomic understanding of this emerging class of anthropogenic nanopollutants.

Proteostasis of heat shock protein 90 in skeletal muscles of the long-tailed ground squirrel during hibernation

We investigated changes in the content of heat shock protein 90 in m. soleus (comprised of mainly fibers expressing the MyHC slow isoform I) and m. gastrocnemius (composed of mainly fibers expressing the MyHC fast isoforms II) of the long-tailed ground squirrel Urocitellus undulatus in different periods of the annual cycle: summer activity (seasonal control), hypothermia/torpor, winter (interbout) activity. The content of the protein in both muscles was found not to change throughout the entire hibernation period despite the development of atrophic changes, more pronounced in fast m. gastrocnemius. The role of HSP90 in maintaining the stability of giant sarcomeric titin protein molecules is discussed with reference to animal's entry into and exit from hypothermia, when the activity of calpain proteases increases due to the increased content of Ca2+ in the cytosol of muscle cells; and with respect to the torpor, when the activity of calpains is, most likely, not inhibited completely. During the interbout activity with an observed increased titin turnover in squirrel's striated muscles, a constant content of HSP90 appears to be required for the correct folding of newly synthesized titin molecules and their integration into sarcomeres, as well as for the removal of misfolded titin molecules and other proteins. Thus, HSP90 proteostasis in skeletal muscles of the long-tailed ground squirrel can contribute to maintaining a steady-state level of titin and, possibly, other sarcomeric proteins during hibernation, which, in turn, will contribute to maintaining a highly ordered sarcomeric structure and the necessary level of muscle contractile activity in different phases of the torpor-arousal cycle.

Increasing muscle contractility through low-frequency stimulation alters tibial bone geometry and reduces bone strength in mdx and dko dystrophic mice.

Duchenne muscular dystrophy (DMD) is a severe muscle wasting disease caused by mutations or deletions in the dystrophin gene, for which there remains no cure. As DMD patients also develop bone fragility because of muscle weakness and immobilization, better understanding of the pathophysiological mechanisms of dystrophin deficiency will help develop therapies to improve musculoskeletal health. Since alterations in muscle phenotype can influence bone structure, we investigated whether modifying muscle contractile activity through low-frequency stimulation (LFS) could alter bone architecture in mouse models of DMD. We tested the hypothesis that increasing muscle contractile activity could influence bone mass and structure in dystrophin-deficient (mdx) and dystrophin- and utrophin-deficient (dko) dystrophic mice. Tibial bone structure in dko mice was significantly different from that in mdx and wild-type (C57BL/10) control mice. Effects of LFS on bone architecture differed between dystrophic and healthy mice, with LFS thinning cortical bone in both dystrophic models. Bone mass was maintained in LFS-treated healthy mice, with a reduced proportion of high-density bone and concomitant increase in low-density bone. LFS-treated dko mice exhibited a net deficit in cortical thickness and reduced high-density bone but no equivalent increase in low-density bone. These alterations in bone structure and mineral density reduced mechanical strength in mdx and dko mice. The findings reveal that muscle activity can regulate bone mass, structure, mineral accrual, and strength, especially in the context of dystrophin and/or utrophin deficiency. The results provide unique insights into the development of bone fragility in DMD and for devising interventions to improve musculoskeletal health.NEW & NOTEWORTHY Patients with Duchenne muscular dystrophy (DMD) develop bone fragility because of muscle weakness and immobilization. We investigated whether increasing muscle contractile activity through low-frequency stimulation (LFS) could alter bone architecture in dystrophin-deficient (mdx) or dystrophin- and utrophin-deficient (dko) mouse models of DMD. Chronic LFS reduced tibial diaphysis cross sections in mdx and dko mice, without affecting bone shape in healthy mice. LFS affected the distribution of bone mineral density across all phenotypes, with the magnitude of effect being dependent on disease severity.

Platelet-activating factor (PAF) enhances guinea pig detrusor smooth muscle contractile activities by stimulating voltage-dependent Ca2+ channels and store-operated Ca2+ channels

We investigated the extracellular Ca2+ influx pathways involved in platelet-activating factor (PAF)-enhanced guinea pig detrusor smooth muscle (DSM) contractile activities. One micromolar PAF-enhanced DSM contractile activities were completely inhibited by extracellular Ca2+ removal and strongly suppressed by voltage-dependent Ca2+ channel (VDCC) inhibitors. PAF-enhanced DSM contractile activities remaining in the presence of verapamil (10 μM) were not inhibited by LOE-908 (30 μM, an inhibitor of receptor-operated Ca2+ channels (ROCCs)), but were almost completely inhibited by SKF-96365 (30 μM, an inhibitor of store-operated Ca2+ channels (SOCCs) and ROCCs). These results suggest that VDCCs and SOCCs are responsible for PAF-enhanced DSM contractile activities.

Estimation of Muscle Fiber Direction by Multi-channel Surface EMG Conductiong Wave Analysis Using Grid Surface Electrodes

Skeletal muscle is a set of motor units (MU). Muscle contractile activity is carried out by regulating the firing frequency of MU and the types of muscle fibers to be mobilized. Multi-channel surface electromyogram (sEMG) contains many conducting waves that represent a single motor unit action potentials (MUAP). In previous study, we proposed a method to extract conducting waves quantitatively and automatically. This method is useful for elucidating mobilized MUs and can be applied to kinematic analysis and diagnosis of muscle diseases. In multi-channel sEMG measurement, rows of electrodes need to be applied along the direction of the muscle fibers. However, the electrodes are difficult to set because the direction of the muscle fibers cannot be visually confirmed on the skin. This study investigated a method for estimating muscle fiber direction by analyzing conducting waves from two-dimensional multichannel surface electromyograms using grid-shaped surface electrodes. By examining the number of conducting waves acquired in each direction of the electrode row, it was suggested that the direction of muscle fiber may be estimated from the direction with the largest number of propagating wave acquisitions. It was also found that the method of acquiring differential potential signals has a significant impact on the analysis of propagation direction.

Effects of CX3CR1 and CXCR2 antagonists on running-dependent intramuscular neutrophil recruitments and myokine upregulation.

Muscle contractile activity stimulates intramuscular recruitment of immune cells including neutrophils emerging to serve as a prerequisite for exerting proper muscular performance, although the underlying mechanisms and their contributions to myokine upregulation remain ill-defined. We previously reported that pharmacological inhibition of CX3CR1, a fractalkine receptor, dampens gnawing-dependent neutrophil recruitment into masseter muscles along with compromising their masticatory activity. By using a running exercise model, we herein demonstrated that hindlimb muscles require collaborative actions of both CX3CR1- and CXCR2-mediated signals for achieving neutrophil recruitment, upregulation of myokines including interleukin (IL)-6, enhanced GLUT4 translocation, and adequate endurance capability. Mechanistically, we revealed that a combination of CX3CR1 and CXCR2 antagonists, i.e., AZD8797 and SB2205002, inhibits exercise-inducible ICAM-1 and fractalkine upregulations in the area of the endothelium and muscle-derived CXCL1 upregulation, both of which apparently contribute to the intramuscular neutrophil accumulation in working muscles. Intriguingly, we also observed that 2 h of running results in intramuscular augmentation of innate lymphoid type 2 cells (ILC2s) markers, i.e., Bcl11b mRNA levels and anti-GATA-3-antibody-positive signals, and that these effects are completely abolished by administration of the combination of CX3CR1 and CXCR2 antagonists. Taken together, our findings strongly suggest that the exercise-evoked regional interplay among working myofibers, the adjacent endothelium, and recruited immune cells including neutrophils and possibly ILC2s, mediated through these local factors, plays a key role in the organization of the intramuscular microenvironment supporting the performance of hindlimb muscles during running.NEW & NOTEWORTHY This study provides compelling evidence that running-dependent intramuscular neutrophil recruitment requires both CX3CR1- and CXCR2-mediated signals that prime not only myofiber-derived myokine upregulations but also endothelium ICAM-1 and fractalkine expressions. The results revealed the importance of the exercise-evoked regional interplay among working myofibers, the adjacent endothelium, and recruited immune cells, including neutrophils and possibly ILC2s, which plays a key role in the organization of the intramuscular microenvironment supporting the performance of hindlimb muscles during running.

Probenecid affects muscle Ca2+ homeostasis and contraction independently from pannexin channel block.

Tight control of skeletal muscle contractile activation is secured by the excitation-contraction (EC) coupling protein complex, a molecular machinery allowing the plasma membrane voltage to control the activity of the ryanodine receptor Ca2+ release channel in the sarcoplasmic reticulum (SR) membrane. This machinery has been shown to be intimately linked to the plasma membrane protein pannexin-1 (Panx1). We investigated whether the prescription drug probenecid, a widely used Panx1 blocker, affects Ca2+ signaling, EC coupling, and muscle force. The effect of probenecid was tested on membrane current, resting Ca2+, and SR Ca2+ release in isolated mouse muscle fibers, using a combination of whole-cell voltage-clamp and Ca2+ imaging, and on electrically triggered contraction of isolated muscles. Probenecid (1 mM) induces SR Ca2+ leak at rest and reduces peak voltage-activated SR Ca2+ release and contractile force by 40%. Carbenoxolone, another Panx1 blocker, also reduces Ca2+ release, but neither a Panx1 channel inhibitory peptide nor a purinergic antagonist affected Ca2+ release, suggesting that probenecid and carbenoxolone do not act through inhibition of Panx1-mediated ATP release and consequently altered purinergic signaling. Probenecid may act by altering Panx1 interaction with the EC coupling machinery, yet the implication of another molecular target cannot be excluded. Since probenecid has been used both in the clinic and as a masking agent for doping in sports, these results should encourage evaluation of possible effects on muscle function in treated individuals. In addition, they also raise the question of whether probenecid-induced altered Ca2+ homeostasis may be shared by other tissues.

The role of intracellular calcium and Rho kinase pathways in G protein-coupled receptor-mediated contractions of urinary bladder urothelium and lamina propria.

The influence of extracellular and intracellular calcium on smooth muscle contractile activity varies between organs. In response to G protein-coupled receptor (GPCR) stimulation, the urinary bladder detrusor muscle has shown a 70% dependence on extracellular calcium, whereas the urothelium and lamina propria (U&LP) has a 20%-50% dependence. However, as this only accounts for partial contractile activity, the contribution of intracellular calcium and calcium sensitization pathways remains unclear. This study assessed the role of intracellular signaling pathways on GPCR-mediated urinary bladder U&LP contraction. Porcine U&LP responses to activation of the Gq/11-coupled muscarinic, histamine, 5-hydroxytryptamine (serotonin), neurokinin, prostaglandin, and angiotensin II receptors were assessed with three selective inhibitors of store-released intracellular calcium, 2-aminoethyl diphenylborinate (2-APB), cyclopiazonic acid (CPA), and ruthenium red, and three Rho kinase inhibitors, fasudil, Y-27632, and GSK269962. There was no discernible impact on receptor agonist-induced contractions of the U&LP after blocking intracellular calcium pathways, suggesting that this tissue is more sensitive to alterations in the availability of extracellular calcium. However, an alternative mechanism of action for GPCR-mediated contraction was identified to be the activation of Rho kinase, such as when Y-27632 significantly reduced the GPCR-mediated contractile activity of the U&LP by approximately 50% (P < 0.05, n = 8). This suggests that contractile responses of the bladder U&LP do not involve a significant release of calcium from intracellular stores, but that Gq/11-coupled receptor activation causes calcium sensitization via Rho kinase. This study highlights a key role for Rho kinase in the urinary bladder, which may provide a novel target in the future pharmaceutical management of bladder contractile disorders.

Physical Activity Increases Immunity to COVID-19 Infection.

Coronavirus are truly one of the maximum critical fantastic-stranded non-segmented RNA viruses, named after the approximately 126-nm-diameter envelope around the nucleic acid-protein complicated. The virus causes significant harm to human fitness, including direct injury to the respiratory system, immune system compromise, worsening of the underlying clinical conditions, and eventually systemic failure and death. Exercise affects the immune system's antiviral mechanisms. Modest exercise, done before or after infection, improves morbidity and mortality to the contamination, according to animal investigations using influenza and simplex virus in the respiratory tract. Moreover, preclinical research has demonstrated that overtraining has a negative impact on the body's response to viral infections. Follow-up research has shed some light on the mechanisms underlying these discoveries. Through the activation of muscle protein synthesis, physical activity (PA) and exercise are essential for maintaining muscle mass. On the other hand, a lack of muscle contractile activity throughout the country of no exercise, particularly in elderly people, is a major contributor to anabolic rigidity and muscle atrophy.

Inhibition of uterine contractility by guanine-based purines in non-pregnant rats.

Growing evidence pointed out that guanine-based purines are able to modulate smooth muscle contractile activity of blood vessels and gastrointestinal tract. Since, so far, possible guanine-based purine modulation of uterine musculature is unknown, the aim of the present study was to investigate in vitro, using organ bath technique, guanosine and guanine effects on spontaneous uterine contraction, and uterine contraction induced by K+-depolarization and oxytocin in a non-pregnant rat. Guanosine, but not guanine, reduced the amplitude of spontaneous contraction of the uterine muscle in a dose-dependent manner. The inhibitory response was antagonized by S-(4-nitrobenzyl)-6-thioinosine (NBTI), a membrane nucleoside transporter inhibitor, but persisted in the presence of theophylline, a nonselective adenosine receptor antagonist, or propanolol, β1/β2 adrenoreceptor antagonist or blockers of a nitrergic pathway. In addition, potassium channel blockers did not influence guanosine-induced effects. Guanosine was able to inhibit the external calcium (Ca2+) influx-induced contraction, but it did not affect the contraction induced by high-KCl solution, indicating that guanosine does not interact with L-type voltage-gated calcium channel. Guanosine prevented/reduced uterine contractions induced by oxytocin, even in the absence of external calcium. In conclusion, guanosine is able to reduce both spontaneous and oxytocin-induced contractions of rat myometrium, likely subsequently to its intracellular intake. The blockade of extracellular Ca2+ influx and reduction of Ca2+ release from the intracellular store are the mechanisms involved in the guanosine-induced tocolytic effects.

Bioactive Metabolites from the Fruiting Body and Mycelia of Newly-Isolated Oyster Mushroom and Their Effect on Smooth Muscle Contractile Activity.

Higher basidiomycetes are recognized as functional foods due to their bioactive compound content, which exerts various beneficial effects on human health, and which have been used as sources for the development of natural medicines and nutraceuticals for centuries. The aim of this study was to evaluate and compare the biological potential of basidiocarp and mycelial biomass produced by submerged cultivation of a new regionally isolated oyster mushroom. The strain was identified with a high percentage of confidence (99.30%) as Pleurotus ostreatus and was deposited in the GenBank under accession number MW 996755. The β-glucan content in the basidiocarp and the obtained mycelial biomass was 31.66% and 12.04%, respectively. Three mycelial biomass and basidiocarp extracts were prepared, and the highest total polyphenol content (5.68 ± 0.15 mg GAE/g DW and 3.20 ± 0.04 mg GAE/g DW) was found in the water extract for both the fruiting body and the mycelium biomass. The in vitro antioxidant activity of the extracts was investigated, and it was determined that the water extracts exhibited the most potent radical scavenging activity. The potential ability of this new fungal isolate to affect the contractile activity (CA) of dissected smooth muscle preparations (SMP) was examined for the first time. It was found that oyster mushrooms likely exhibit indirect contractile effects on the gastric smooth muscle (SM) cells.

Effects of Physical Exercise on Metabolic Diseases

Physical activity and diabetes have been linked, as it plays an important role in preventing the progression of peripheral neuropathy, and their impact is primarily on the development of muscle strength and the ability to replace the function of nerve fibers with impaired disabilities. It seems that any form of exercise added to a balanced lifestyle significantly improves the quality of the subject with diabetes (type 2 diabetes). The small differences between aerobic and endurance training as a benefit for type 2 diabetes do not promote a certain form of exercise. In conclusion, the effects of regular exercise are recognized as an effective way to improve the condition of the disease. The basis of exercise therapy is simply the ability of skeletal muscle contractile activity to increase insulin sensitivity and promote blood glucose absorption and stabilization. Thus, regular participation in aerobic structure, endurance, or competing exercise had generally favorable effects on glycemic control, body composition, endothelial function, physical work capacity, and self-reported well-being.

Regulation of Papillary Muscle Contractility by NAD and Ammonia Interplay: Contribution of Ion Channels and Exchangers.

Various models, including stem cells derived and isolated cardiomyocytes with overexpressed channels, are utilized to analyze the functional interplay of diverse ion currents involved in cardiac automaticity and excitation-contraction coupling control. Here, we used β-NAD and ammonia, known hyperpolarizing and depolarizing agents, respectively, and applied inhibitory analysis to reveal the interplay of several ion channels implicated in rat papillary muscle contractility control. We demonstrated that: 4 mM β-NAD, having no strong impact on resting membrane potential (RMP) and action potential duration (APD90) of ventricular cardiomyocytes, evoked significant suppression of isometric force (F) of paced papillary muscle. Reactive blue 2 restored F to control values, suggesting the involvement of P2Y-receptor-dependent signaling in β-NAD effects. Meantime, 5 mM NH4Cl did not show any effect on F of papillary muscle but resulted in significant RMP depolarization, APD90 shortening, and a rightward shift of I-V relationship for total steady state currents in cardiomyocytes. Paradoxically, NH4Cl, being added after β-NAD and having no effect on RMP, APD, and I-V curve, recovered F to the control values, indicating β-NAD/ammonia antagonism. Blocking of HCN, Kir2.x, and L-type calcium channels, Ca2+-activated K+ channels (SK, IK, and BK), or NCX exchanger reverse mode prevented this effect, indicating consistent cooperation of all currents mediated by these channels and NCX. We suggest that the activation of Kir2.x and HCN channels by extracellular K+, that creates positive and negative feedback, and known ammonia and K+ resemblance, may provide conditions required for the activation of all the chain of channels involved in the interplay. Here, we present a mechanistic model describing an interplay of channels and second messengers, which may explain discovered antagonism of β-NAD and ammonia on rat papillary muscle contractile activity.

RSPO3 is a novel contraction-inducible factor identified in an “in vitro exercise model” using primary human myotubes

The physiological significance of skeletal muscle as a secretory organ is now well known but we can only speculate as to the existence of as-yet-unidentified myokines, especially those upregulated in response to muscle contractile activity. We first attempted to establish an “insert-chamber based in vitro exercise model” allowing the miniature but high cell-density culture state enabling highly developed contractile human myotubes to be readily obtained by applying electric pulse stimulation (EPS). By employing this in vitro exercise model, we identified R-spondin 3 (RSPO3) as a novel contraction-inducible myokine produced by cultured human myotubes. Contraction-dependent muscular RSPO3 mRNA upregulation was confirmed in skeletal muscles of mice subjected to sciatic nerve mediated in situ contraction as well as those of mice after 2 h of running. Pharmacological in vitro experiments demonstrated a relatively high concentration of metformin (millimolar range) to suppress the contraction-inducible mRNA upregulation of human myokines including RSPO3, interleukin (IL)-6, IL-8 and CXCL1. Our data also suggest human RSPO3 to be a paracrine factor that may positively participate in the myogenesis processes of myoblasts and satellite cells. Thus, the “insert chamber-based in vitro exercise model” is a potentially valuable research tool for investigating contraction-inducible biological responses of human myotubes usually exhibiting poorer contractility development even in the setting of EPS treatment.

Roles of ATP and SERCA in the Regulation of Calcium Turnover in Unloaded Skeletal Muscles: Current View and Future Directions.

A decrease in skeletal muscle contractile activity or its complete cessation (muscle unloading or disuse) leads to muscle fibers’ atrophy and to alterations in muscle performance. These changes negatively affect the quality of life of people who, for one reason or another, are forced to face a limitation of physical activity. One of the key regulatory events leading to the muscle disuse-induced changes is an impairment of calcium homeostasis, which leads to the excessive accumulation of calcium ions in the sarcoplasm. This review aimed to analyze the triggering mechanisms of calcium homeostasis impairment (including those associated with the accumulation of high-energy phosphates) under various types of muscle unloading. Here we proposed a hypothesis about the regulatory mechanisms of SERCA and IP3 receptors activity during muscle unloading, and about the contribution of these mechanisms to the excessive calcium ion myoplasmic accumulation and gene transcription regulation via excitation–transcription coupling.

Real Time and Repeated Measurement of Skeletal Muscle Growth in Individual Live Zebrafish Subjected to Altered Electrical Activity

A number of methods can be used to visualize individual cells throughout the body of live embryonic, larval or juvenile zebrafish. We show that live fish with fluorescently-marked plasma membranes can be scanned in a confocal laser scanning microscope in order to determine the volume of muscle tissue and the number of muscle fibers present. Efficient approaches for the measurement of cell number and size in live animals over time are described and validated against more arduous segmentation methods. Methods are described that permit the control of muscle electrical, and thus contractile, activity. Loss of skeletal muscle contractile activity greatly reduced muscle growth. In larvae, a protocol is described that allows reintroduction of patterned electrical-evoked contractile activity. The described methods minimize the effect of inter-individual variability and will permit analysis of the effect of electrical, genetic, drug, or environmental stimuli on a variety of cellular and physiological growth parameters in the context of the living organism. Long-term follow-up of the measured effects of a defined early-life intervention on individuals can subsequently be performed.

Disuse-induced skeletal muscle atrophy in disease and nondisease states in humans: mechanisms, prevention, and recovery strategies.

Decreased skeletal muscle contractile activity (disuse) or unloading leads to muscle mass loss, also known as muscle atrophy. The balance between muscle protein synthesis (MPS) and muscle protein breakdown (MPB) is the primary determinant of skeletal muscle mass. A reduced mechanical load on skeletal muscle is one of the main external factors leading to muscle atrophy. However, endocrine and inflammatory factors can act synergistically in catabolic states, amplifying the atrophy process and accelerating its progression. In addition, older individuals display aging-induced anabolic resistance, which can predispose this population to more pronounced effects when exposed to periods of reduced physical activity or mechanical unloading. Different cellular mechanisms contribute to the regulation of muscle protein balance during skeletal muscle atrophy. This review summarizes the effects of muscle disuse on muscle protein balance and the molecular mechanisms involved in muscle atrophy in the absence or presence of disease. Finally, a discussion of the current literature describing efficient strategies to prevent or improve the recovery from muscle atrophy is also presented.