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Clinical Neurophysiology : Official... Aug 2019This document is the consensus of international experts on the current status of Single Fiber EMG (SFEMG) and the measurement of neuromuscular jitter with concentric... (Review)
Review
This document is the consensus of international experts on the current status of Single Fiber EMG (SFEMG) and the measurement of neuromuscular jitter with concentric needle electrodes (CNE - CN-jitter). The panel of authors was chosen based on their particular interests and previous publications within a specific area of SFEMG or CN-jitter. Each member of the panel was asked to submit a section on their particular area of interest and these submissions were circulated among the panel members for edits and comments. This process continued until a consensus was reached. Donald Sanders and Erik Stålberg then edited the final document.
Topics: Animals; Electrodes; Electromyography; Humans; Myofibrils; Neuromuscular Junction; Practice Guidelines as Topic
PubMed: 31080019
DOI: 10.1016/j.clinph.2019.04.005 -
Nature Reviews. Drug Discovery Jan 2015Atrophy occurs in specific muscles with inactivity (for example, during plaster cast immobilization) or denervation (for example, in patients with spinal cord injuries).... (Review)
Review
Atrophy occurs in specific muscles with inactivity (for example, during plaster cast immobilization) or denervation (for example, in patients with spinal cord injuries). Muscle wasting occurs systemically in older people (a condition known as sarcopenia); as a physiological response to fasting or malnutrition; and in many diseases, including chronic obstructive pulmonary disorder, cancer-associated cachexia, diabetes, renal failure, cardiac failure, Cushing syndrome, sepsis, burns and trauma. The rapid loss of muscle mass and strength primarily results from excessive protein breakdown, which is often accompanied by reduced protein synthesis. This loss of muscle function can lead to reduced quality of life, increased morbidity and mortality. Exercise is the only accepted approach to prevent or slow atrophy. However, several promising therapeutic agents are in development, and major advances in our understanding of the cellular mechanisms that regulate the protein balance in muscle include the identification of several cytokines, particularly myostatin, and a common transcriptional programme that promotes muscle wasting. Here, we discuss these new insights and the rationally designed therapies that are emerging to combat muscle wasting.
Topics: Animals; Humans; Muscular Atrophy; Myofibrils; Myostatin; Quality of Life; Sepsis; Signal Transduction; Wasting Syndrome
PubMed: 25549588
DOI: 10.1038/nrd4467 -
Circulation. Genomic and Precision... Oct 2020Pathogenic variants in , encoding cardiac MyBP-C (myosin binding protein C), are the most common cause of familial hypertrophic cardiomyopathy. A large number of unique...
BACKGROUND
Pathogenic variants in , encoding cardiac MyBP-C (myosin binding protein C), are the most common cause of familial hypertrophic cardiomyopathy. A large number of unique variants and relatively small genotyped hypertrophic cardiomyopathy cohorts have precluded detailed genotype-phenotype correlations.
METHODS
Patients with hypertrophic cardiomyopathy and variants were identified from the Sarcomeric Human Cardiomyopathy Registry. Variant types and locations were analyzed, morphological severity was assessed, and time-event analysis was performed (composite clinical outcome of sudden death, class III/IV heart failure, left ventricular assist device/transplant, atrial fibrillation). For selected missense variants falling in enriched domains, myofilament localization and degradation rates were measured in vitro.
RESULTS
Among 4756 genotyped patients with hypertrophic cardiomyopathy in Sarcomeric Human Cardiomyopathy Registry, 1316 patients were identified with adjudicated pathogenic truncating (N=234 unique variants, 1047 patients) or nontruncating (N=22 unique variants, 191 patients) variants in . Truncating variants were evenly dispersed throughout the gene, and hypertrophy severity and outcomes were not associated with variant location (grouped by 5'-3' quartiles or by founder variant subgroup). Nontruncating pathogenic variants clustered in the C3, C6, and C10 domains (18 of 22, 82%, <0.001 versus Genome Aggregation Database common variants) and were associated with similar hypertrophy severity and adverse event rates as observed with truncating variants. MyBP-C with variants in the C3, C6, and C10 domains was expressed in rat ventricular myocytes. C10 mutant MyBP-C failed to incorporate into myofilaments and degradation rates were accelerated by ≈90%, while C3 and C6 mutant MyBP-C incorporated normally with degradation rate similar to wild-type.
CONCLUSIONS
Truncating variants account for 91% of pathogenic variants and cause similar clinical severity and outcomes regardless of location, consistent with locus-independent loss-of-function. Nontruncating pathogenic variants are regionally clustered, and a subset also cause loss of function through failure of myofilament incorporation and rapid degradation. Cardiac morphology and clinical outcomes are similar in patients with truncating versus nontruncating variants.
Topics: Adolescent; Adult; Cardiomyopathy, Hypertrophic; Carrier Proteins; Child; Female; Genotype; Humans; Male; Middle Aged; Myofibrils; Phenotype; Polymorphism, Genetic; Registries; Severity of Illness Index; Spatial Analysis; Young Adult
PubMed: 32841044
DOI: 10.1161/CIRCGEN.120.002929 -
Advances in Experimental Medicine and... 2018Muscle tissue is a highly specialized type of tissue, made up of cells that have as their fundamental properties excitability and contractility. The cellular elements... (Review)
Review
Muscle tissue is a highly specialized type of tissue, made up of cells that have as their fundamental properties excitability and contractility. The cellular elements that make up this type of tissue are called muscle fibers, or myofibers, because of the elongated shape they have. Contractility is due to the presence of myofibrils in the muscle fiber cytoplasm, as large cellular assemblies. Also, myofibers are responsible for the force that the muscle generates which represents a countless aspect of human life. Movements due to muscles are based on the ability of muscle fibers to use the chemical energy procured in metabolic processes, to shorten and then to return to the original dimensions. We describe in detail the levels of organization for the myofiber, and we correlate the structural aspects with the functional ones, beginning with neuromuscular transmission down to the biochemical reactions achieved in the sarcoplasmic reticulum by the release of Ca and the cycling of crossbridges. Furthermore, we are reviewing the types of muscle contractions and the fiber-type classification.
Topics: Animals; Humans; Muscle Contraction; Muscles; Myofibrils; Sarcoplasmic Reticulum
PubMed: 30390246
DOI: 10.1007/978-981-13-1435-3_2 -
The Journal of Clinical Investigation May 2022Passive stiffness of the heart is determined largely by extracellular matrix and titin, which functions as a molecular spring within sarcomeres. Titin stiffening is...
Passive stiffness of the heart is determined largely by extracellular matrix and titin, which functions as a molecular spring within sarcomeres. Titin stiffening is associated with the development of diastolic dysfunction (DD), while augmented titin compliance appears to impair systolic performance in dilated cardiomyopathy. We found that myofibril stiffness was elevated in mice lacking histone deacetylase 6 (HDAC6). Cultured adult murine ventricular myocytes treated with a selective HDAC6 inhibitor also exhibited increased myofibril stiffness. Conversely, HDAC6 overexpression in cardiomyocytes led to decreased myofibril stiffness, as did ex vivo treatment of mouse, rat, and human myofibrils with recombinant HDAC6. Modulation of myofibril stiffness by HDAC6 was dependent on 282 amino acids encompassing a portion of the PEVK element of titin. HDAC6 colocalized with Z-disks, and proteomics analysis suggested that HDAC6 functions as a sarcomeric protein deacetylase. Finally, increased myofibril stiffness in HDAC6-deficient mice was associated with exacerbated DD in response to hypertension or aging. These findings define a role for a deacetylase in the control of myofibril function and myocardial passive stiffness, suggest that reversible acetylation alters titin compliance, and reveal the potential of targeting HDAC6 to manipulate the elastic properties of the heart to treat cardiac diseases.
Topics: Animals; Connectin; Histone Deacetylase 6; Humans; Mice; Myocardium; Myocytes, Cardiac; Myofibrils; Rats; Sarcomeres
PubMed: 35575093
DOI: 10.1172/JCI148333 -
Cells & Development Dec 2021Muscles generate forces for animal locomotion. The contractile apparatus of muscles is the sarcomere, a highly regular array of large actin and myosin filaments linked... (Review)
Review
Muscles generate forces for animal locomotion. The contractile apparatus of muscles is the sarcomere, a highly regular array of large actin and myosin filaments linked by gigantic titin springs. During muscle development many sarcomeres assemble in series into long periodic myofibrils that mechanically connect the attached skeleton elements. Thus, ATP-driven myosin forces can power movement of the skeleton. Here we review muscle and myofibril morphogenesis, with a particular focus on their mechanobiology. We describe recent progress on the molecular structure of sarcomeres and their mechanical connections to the skeleton. We discuss current models predicting how tension coordinates the assembly of key sarcomeric components to periodic myofibrils that then further mature during development. This requires transcriptional feedback mechanisms that may help to coordinate myofibril assembly and maturation states with the transcriptional program. To fuel the varying energy demands of muscles we also discuss the close mechanical interactions of myofibrils with mitochondria and nuclei to optimally support powerful or enduring muscle fibers.
Topics: Animals; Biophysics; Morphogenesis; Myofibrils; Myosins; Sarcomeres
PubMed: 34863916
DOI: 10.1016/j.cdev.2021.203760 -
Mechanisms of Development Apr 2017Muscles are the major force producing tissue in the human body. While certain muscle types specialize in producing maximum forces, others are very enduring. An extreme... (Review)
Review
Muscles are the major force producing tissue in the human body. While certain muscle types specialize in producing maximum forces, others are very enduring. An extreme example is the heart, which continuously beats for the entire life. Despite being specialized, all body muscles share similar contractile mini-machines called sarcomeres that are organized into regular higher order structures called myofibrils. The major sarcomeric components and their organizational principles are conserved throughout most of the animal kingdom. In this review, we discuss recent progress in the understanding of myofibril and sarcomere development largely obtained from in vivo models. We focus on the role of mechanical forces during muscle and myofibril development and propose a tension driven self-organization mechanism for myofibril formation. We discuss recent technological advances that allow quantification of forces across tissues or molecules in vitro and in vivo. Although their application towards muscle development is still in its infancy, these technologies are likely to provide fundamental new insights into the mechanobiology of muscle and myofibril development in the near future.
Topics: Actins; Animals; Biomechanical Phenomena; Connectin; Drosophila melanogaster; Gene Expression Regulation, Developmental; Humans; Integrins; Muscle Development; Muscle Tonus; Myofibrils; Signal Transduction; Tendons
PubMed: 27913119
DOI: 10.1016/j.mod.2016.11.003 -
Archives of Biochemistry and Biophysics Mar 2019Mitochondria represent the main source of ATP in skeletal muscle and mitochondria activity increases after muscle fiber depolarization. The regulation of mitochondrial... (Review)
Review
Mitochondria represent the main source of ATP in skeletal muscle and mitochondria activity increases after muscle fiber depolarization. The regulation of mitochondrial function during contraction in skeletal muscle, however, is poorly understood. Skeletal muscle has a particular distribution of mitochondria where three distinct populations can be recognized. The most studied populations are the ones positioned deep into the myofibers between the myofibrils (intermyofibrillar mitochondria), and that located immediately beneath sarcolemma (subsarcolemmal mitochondria); a less studied population locates covering the myonuclei, as a continuation of the subsarcolemmal population. All mitochondria populations undergo fusion and fission events and intermyofibrillar mitochondria are interconnected; mitochondrial communication is necessary to maintain not only the energetic homeostasis of the muscle but its contractile function, as well. The mechanism supporting communication between subsarcolemmal and intermyofibrillar mitochondria is unknown. The recently described MCU complex of proteins has provided a new insight into the role of calcium as a regulator of mitochondrial function. Whether the different mitochondria populations have different calcium handling capacity and whether mitochondria Ca has a role in energy transmission along the mitochondria network are intriguing issues that emerge when studying the link between electrical stimulation of the muscle fiber and the mitochondria metabolic output.
Topics: Animals; Energy Metabolism; Homeostasis; Humans; Mitochondria, Muscle; Mitochondrial Proteins; Muscle, Skeletal; Myofibrils
PubMed: 30716283
DOI: 10.1016/j.abb.2019.01.037 -
American Journal of Physiology. Cell... Nov 2023Muscular dystrophy exerts significant and dramatic impacts on affected patients, including progressive muscle wasting leading to lung and heart failure, and results in... (Review)
Review
Muscular dystrophy exerts significant and dramatic impacts on affected patients, including progressive muscle wasting leading to lung and heart failure, and results in severely curtailed lifespan. Although the focus for many years has been on the dysfunction induced by the loss of function of dystrophin or related components of the striated muscle costamere, recent studies have demonstrated that accompanying pathologies, particularly muscle fibrosis, also contribute adversely to patient outcomes. A significant body of research has now shown that therapeutically targeting these accompanying pathologies via their underlying molecular mechanisms may provide novel approaches to patient management that can complement the current standard of care. In this review, we discuss the interplay between muscle fibrosis and muscular dystrophy pathology. A better understanding of these processes will contribute to improved patient care options, restoration of muscle function, and reduced patient morbidity and mortality.
Topics: Humans; Muscular Dystrophy, Duchenne; Muscle, Skeletal; Fibrosis; Myofibrils; Heart Failure
PubMed: 37781738
DOI: 10.1152/ajpcell.00196.2023 -
Revue Neurologique Oct 2016Distal myopathies and myofibrillar myopathies are both rare subcategories of muscle diseases. Myofibrillar myopathies are genetically heterogeneous group of diseases... (Review)
Review
Distal myopathies and myofibrillar myopathies are both rare subcategories of muscle diseases. Myofibrillar myopathies are genetically heterogeneous group of diseases characterized by distinctive histopathology of abnormal protein aggregations and myofibrillar disintegration. All genes causing myofibrillar myopathy encode proteins that either reside in or associate with the Z-disc. Distal myopathies are also genetically heterogeneous muscular dystrophies in which muscle weakness presents distally in the feet and/or hands. A subgroup of distal myopathies, desminopathy, distal myotilinopathy, ZASPopathy and alpha-B crystallin-mutated distal myopathy, belong to myofibrillar myopathies and show similar pathological changes in muscle biopsies. Common features of these diseases are dominant inheritance and adult-onset of symptoms starting in the feet and slowly progressing to encompass other muscle groups. Cardiomyopathy is not a common feature in distal MFM myopathies.
Topics: Distal Myopathies; Humans; Myofibrils
PubMed: 27638134
DOI: 10.1016/j.neurol.2016.07.019