AMP-activated protein kinase (AMPK) is a cellular energy gauge and a major regulator of cellular energy homeostasis. Once activated, AMPK stimulates nutrient uptake and the ATP-producing catabolic pathways, while it suppresses the ATP-consuming anabolic pathways, thus helping to maintain the cellular energy balance under energy-deprived conditions. As much as ~ 20–25% of the whole-body ATP consumption

Phosphorylation of α-tropomyosin (Tpm1.1), a predominant Tpm isoform in the myocardium, is one of the regulatory mechanisms of the heart contractility. The Tpm 1.1 molecule has one site of phosphorylation, Ser283. The degree of the Tpm phosphorylation decreases with age and also changes in heart pathologies. Myocardial pathologies, in particular ischemia, are usually accompanied by pH lowering in the

The highly organized transverse T-tubule membrane system represents the ultrastructural substrate for excitation–contraction coupling in ventricular myocytes. While the architecture and function of T-tubules have been well described in animal models, there is limited morpho-functional data on T-tubules in human myocardium. Hypertrophic cardiomyopathy (HCM) is a primary disease of the heart muscle,

Familial cardiomyopathy is an inherited disease that affects the structure and function of heart muscle and has an extreme range of phenotypes. Among the millions of affected individuals, patients with hypertrophic (HCM), dilated (DCM), or left ventricular non-compaction (LVNC) cardiomyopathy can experience morphologic changes of the heart which lead to sudden death in the most detrimental cases. TNNC1

GNE myopathy is an adult-onset degenerative muscle disease that leads to extreme disability in patients. Biallelic mutations in the rate-limiting enzyme UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine-kinase (GNE) of sialic acid (SA) biosynthetic pathway, was shown to be the cause of this disease. Other genetic disorders with muscle pathology where defects in glycosylation are known. It is

Skeletal muscle satellite cells (SCs) play an important role in the repairment and regeneration of damaged muscle. The activation, proliferation, migration, and differentiation of SCs are essential to the response to muscle injury. Up-frameshift 1 (UPF1) is involved in the regulation of many developmental processes. However, the role of UPF1 and its associated regulatory mechanism in SCs are still

Skeletal muscle atrophy as a consequence of acute and chronic illness, immobilisation, muscular dystrophies and aging, leads to severe muscle weakness, inactivity and increased mortality. Mechanical loading is thought to be the primary driver for skeletal muscle hypertrophy, however the extent to which mechanical loading can offset muscle catabolism has not been thoroughly explored. In vitro 3D-models

Two single mutations, R694N and E45Q, were introduced in the beta isoform of human cardiac myosin to remove permanent salt bridges E45:R694 and E98:R694 in the SH1-SH2 helix of the myosin head. Beta isoform-specific bridges E45:R694 and E98:R694 were discovered in the molecular dynamics simulations of the alpha and beta myosin isoforms. Alpha and beta isoforms exhibit different kinetics, ADP dissociates

Homozygous calsequestrin 2 (CASQ2) point mutations leads to catecholaminergic polymorphic ventricular tachycardia: a common pathogenetic feature appears to be the drastic reduction of mutant CASQ2 in spite of normal transcription. Comparative biochemical analysis of R33Q and D307H knock in mutant mice identifies different pathogenetic mechanisms for CASQ2 degradation and different molecular adaptive

In the last decades the term Store-operated Ca2+ entry (SOCE) has been used in the scientific literature to describe an ubiquitous cellular mechanism that allows recovery of calcium (Ca2+) from the extracellular space. SOCE is triggered by a reduction of Ca2+ content (i.e. depletion) in intracellular stores, i.e. endoplasmic or sarcoplasmic reticulum (ER and SR). In skeletal muscle the mechanism is

To improve muscle healing upon injury, it is of importance to understand the interplay of key signaling pathways during muscle regeneration. To study this, mice were injected with cardiotoxin (CTX) or PBS in the Tibialis Anterior muscle and were sacrificed 2, 5 and 12 days upon injection. The time points represent different phases of the regeneration process, i.e. destruction, repair and remodeling

Calsequestrin (CASQ) is the most abundant Ca2+ binding protein localized in the sarcoplasmic reticulum (SR) of skeletal and cardiac muscle. The genome of vertebrates contains two genes, CASQ1 and CASQ2. CASQ1 and CASQ2 have a high level of homology, but show specific patterns of expression. Fast-twitch skeletal muscle fibers express only CASQ1, both CASQ1 and CASQ2 are present in slow-twitch skeletal

ACTN2 and ACTN3 encode sarcomeric α-actinin-2 and α-actinin-3 proteins, respectively, that constitute the Z-line in mammalian skeletal muscle fibers. In human ACTN3, a nonsense mutation at codon 577 that encodes arginine (R) produces the R577X polymorphism. Individuals having a homozygous 577XX genotype do not produce α-actinin-3 protein. The 577XX genotype reportedly occurs in sprint and power athletes

This study reports that in rat skeletal muscle the proteins specifically responsible for mitochondrial dynamics, mitofusin-2 (MFN2) and mitochondrial dynamics protein 49 (MiD49), are higher (p < 0.05) in oxidative soleus (SOL) muscle compared with predominantly glycolytic extensor digitorum longus (EDL) muscle, but not seen for optic atrophy 1 (OPA1; p = 0.06). Markers of mitochondrial content, complex

Abstract Muscle contracture development is a major complication for individuals with cerebral palsy (CP) and has lifelong implications. In order to recognize contracture development early and to follow up on preventive interventions aimed at muscle health development, non-invasive, and easy to use methods are needed. The aim of the present study was to assess whether multi-frequency Bioimpedance (mfBIA)

Abstract Melatonin (N-acetyl-5-methoxy-tryptamine) is an effective antioxidant and free radical scavenger, that has important biological effects in multiple cell types and species. Melatonin research in muscle has recently gained attention, mainly focused on its role in cells or tissue repair and regeneration after injury, due to its powerful biological functions, including its antioxidant, anti-inflammation

Cerebral palsy (CP) is a neurodevelopmental disorder characterized by abnormalities of muscle tone, movement and motor skills, and is attributed to injury to the developing brain. CP affects about 1 in 500 neonates. CP shows clinical features which evolve with age, and these may over time lead to deterioration of motor function although the lesion to the developing brain is non-progressive. The underlying

A testable molecular proposal for the effects of acidosis on skeletal and cardiac muscle is presented. It is based on fluorescence studies published in 1974, which provided evidence for carboxylates in an EF-hand Ca2+ binding site having an abnormal pKa. This results in an H+-bound Blocked substate in the 3-state model of muscle regulation whose contribution inhibits myosin binding in the pH 7 to 6

Ryanodine receptors (RyRs) are huge homotetrameric Ca2+ release channels localized to the sarcoplasmic reticulum. RyRs are responsible for the release of Ca2+ from the SR during excitation-contraction coupling in striated muscle cells. Recent revolutionary advancements in cryo-electron microscopy have provided a number of near-atomic structures of RyRs, which have enabled us to better understand the

Caffeine is worldwide used for its power to increase cognitive and physical performance. The ergogenic effects of caffeine, however, do not depend on a direct action on muscles. Actually, the actions of caffeine on skeletal muscles, take place at millimolar concentrations which are far above the micromolar level reached after a regular consumption of coffee or similar drinks, and close to a lethal

Nebulin, encoded by NEB, is a giant skeletal muscle protein of about 6669 amino acids which forms an integral part of the sarcomeric thin filament. In recent years, the nebula around this protein has been largely lifted resulting in the discovery that nebulin is critical for a number of tasks in skeletal muscle. In this review, we firstly discussed nebulin’s role as a structural component of the thin

The heart is an extraordinarily versatile pump, finely tuned to respond to a multitude of demands. Given the heart pumps without rest for decades its efficiency is particularly relevant. Although many proteins in the heart are essential for viability, the non-essential components can attract numerous mutations which can cause disease, possibly through alterations in pumping efficiency. Of these, myosin

Appropriate organization of cytoskeletal components are required for normal distribution and intracellular localization of different ion channels and proteins involved in calcium homeostasis, signal transduction, and contractile function of striated muscle. Proteins of the contractile system are in direct or indirect connection with the extrasarcomeric cytoskeleton. A number of other molecules which

Activity dependent potentiation is thought to result from phosphorylation of the regulatory light chains of myosin, increasing Ca2+ sensitivity. Yet, Ca2+ sensitivity decreases early in a period of intermittent contractions. The purpose of this study was to investigate the early change in Ca2+ sensitivity during intermittent submaximal tetanic contractions. Flexor digitorum brevis muscle fibres were

Gelsolin superfamily proteins, consisting of multiple domains (usually six), sever actin filaments and cap the barbed ends in a Ca2+-dependent manner. Two types of evolutionally conserved Ca2+-binding sites have been identified in this family; type-1 (between gelsolin and actin) and type-2 (within the gelsolin domain). Fragmin, a member in the slime mold Physarum polycephalum, consists of three domains

Researchers continue to develop therapeutic products for the repair and replacement of myocardial tissue that demonstrates contractility equivalent to normal physiologic states. As clinical trials focused on pure adult stem cell populations undergo meta-analysis for preclinical through clinical design, the field of tissue engineering is emerging as a new clinical frontier to repair the myocardium and

The serine/threonine kinase AMP-activated protein kinase (AMPK) is a drug target for the treatment of obesity and type 2 diabetes (T2D). Metformin, a widely prescribed anti-hyperglycemic agent, and β-guanidinopropionic acid (β-GPA), a dietary supplement and creatine analog, have been shown to increase activity of AMPK. Macroautophagy is an intracellular degradation pathway for aggregated proteins and

The regulated assembly of actin filaments is essential in nearly all cell types. Studying actin assembly dynamics can pose many technical challenges. A number of these challenges can be overcome by using microfluidics to observe and manipulate single actin filaments under an optical microscope. In particular, microfluidics can be tremendously useful for applying different mechanical stresses to actin

This study investigated the effect of S-glutathionylation on passive force in skeletal muscle fibres, to determine whether activity-related redox reactions could modulate the passive force properties of muscle. Mechanically-skinned fibres were freshly obtained from human and rat muscle, setting sarcomere length (SL) by laser diffraction. Larger stretches were required to produce passive force in human

Ischaemic preconditioning (IPC) protects against myocardial ischaemia-reperfusion injury. The metabolic and ionic effects of IPC remain to be clarified in detail. We aimed to investigate the effect of IPC (2 times 5 min ischaemia) on the subcellular distribution of glycogen and Ca2+-uptake and leakiness by the sarcoplasmic reticulum (SR) in response to ischaemia-reperfusion in cardiomyocytes of isolated

In the heart, mutations in the TPM1 gene encoding the α-isoform of tropomyosin lead, in particular, to the development of hypertrophic and dilated cardiomyopathies. We compared the effects of hypertrophic, D175N and E180G, and dilated, E40K and E54K, cardiomyopathy mutations in TPM1 gene on the properties of single actin–myosin interactions and the characteristics of the calcium regulation in an ensemble

Myopathies are a large and heterogeneous group of disorders associated with mutations in structural and regulatory genes responsible for proper muscle assembly, organization and function. Despite the molecular diversity of inherited myopathies, they have historically been classified by the phenotypic traits observed in affected patients. It is therefore common for myopathies originating from mutations

microRNAs are short, (18–22 nt) non-coding RNAs involved in important cellular processes due to their ability to regulate gene expression at the post-transcriptional level. Exosomes are small (50–200 nm) extracellular vesicles, naturally secreted from a variety of living cells and are believed to mediate cell–cell communication through multiple mechanisms, including uptake in destination cells. Circulating

Calcium plays an essential role in muscle contraction, regulating actomyosin interaction by binding troponin of thin filaments. There are several buffers for calcium in muscle, and those buffers play a crucial role in the formation of the transient calcium wave in sarcomere upon muscle activation. One such calcium buffer in muscle is ATP. ATP is a fuel molecule, and the important role of MgATP in muscle

Tropomyosin is a dimer coiled-coil actin-binding protein. Adjacent tropomyosin molecules connect each other ‘head-to-tail’ via an overlap junction and form a continuous strand that winds around an actin filament and controls the actin–myosin interaction. High cooperativity of muscle contraction largely depends on tropomyosin characteristics. Here we summarise experimental evidence that local peculiarities

The cardiomyocyte plasma membrane, termed the sarcolemma, is fundamental for regulating a myriad of cellular processes. For example, the structural integrity of the cardiomyocyte sarcolemma is essential for mediating cardiac contraction by forming microdomains such as the t-tubular network, caveolae and the intercalated disc. Significantly, remodelling of these sarcolemma microdomains is a key feature

Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) are well-known cytokines with pro-inflammatory capabilities, and have been shown to be involved in adaptation to exercise as multifaceted myokines. However, the precise role of IL-6 and TNF-α during exercise-induced skeletal muscle injury and subsequent repair processes is not fully understood. In this study, IL-6 and TNF-α were examined

Skeletal muscle, the essential organ for locomotion, as well as energy reservoir and expenditure, has robust regenerative capacity in response to mechanical stress and injury. As muscle-specific stem cells, satellite cells are responsible for providing new myoblasts during the process of muscle growth and regeneration. Self-renewal capacity and the fate of satellite cells are highly regulated and influenced

Skeletal muscle fibres are large, elongated multinucleated cells. Each nucleus within a myofibre is responsible for generating gene products for a finite volume of cytoplasm—the myonuclear domain (MND). Variation in MND sizes during atrophy, hypertrophy and disease states, are common. The factors that contribute to definitive MND sizes are not yet fully understood. Previous work has shown that peroxisome

The β-adrenergic receptor stimulation improves endurance in fast twitch muscles and these effects are sensitive to extracellular Ca2+ influx. Present study is aimed to determine the effects of adrenaline, with different concentrations of extracellular Ca2+\(\left( {{\text{Ca}}_{\text{ECF}}^{ 2+ } } \right)\), on the contractility and endurance of slow twitch muscles during high frequency stimulations

Xenografts of skeletal muscle are used to study muscle repair and regeneration, mechanisms of muscular dystrophies, and potential cell therapies for musculoskeletal disorders. Typically, xenografting involves using an immunodeficient host that is pre-injured to create a niche for human cell engraftment. Cell type and method of delivery to muscle depend on the specific application, but can include myoblasts

Skeletal muscles are characterized by their unique regenerative capacity following injury due to the presence of muscle precursor cells, satellite cells. This characteristic allows researchers to study muscle regeneration using experimental injury models. These injury models should be stable and reproducible. Variety of injury models have been used, among which the intramuscular injection of myotoxic

ADF/cofilins disassemble the actin filament and contribute to a wide range of actin dynamics. These proteins are regulated by several factors, including phosphorylation, pH and mechanical forces. Although the cofilin-decorated actin filament structure was published recently, the mechanisms of these regulating factors remain unclear. Models that describe regulation based on the latest structural data

Some vertebrate muscles (e.g. those in bony fish) have a simple lattice A-band which is so well ordered that low-angle X-ray diffraction patterns are sampled in a simple way amenable to crystallographic techniques. Time-resolved X-ray diffraction through the contractile cycle should provide a movie of the molecular movements involved in muscle contraction. Generation of ‘Muscle—The Movie’ was suggested