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Progress in Biophysics and Molecular... 2000Contractile and energetic properties of human skeletal muscle have been studied for many years in vivo in the body. It has been, however, difficult to identify the... (Review)
Review
Contractile and energetic properties of human skeletal muscle have been studied for many years in vivo in the body. It has been, however, difficult to identify the specific role of muscle fibres in modulating muscle performance. Recently it has become possible to dissect short segments of single human muscle fibres from biopsy samples and make them work in nearly physiologic conditions in vitro. At the same time, the development of molecular biology has provided a wealth of information on muscle proteins and their genes and new techniques have allowed analysis of the protein isoform composition of the same fibre segments used for functional studies. In this way the histological identification of three main human muscle fibre types (I, IIA and IIX, previously called IIB) has been followed by a precise description of molecular composition and functional and biochemical properties. It has become apparent that the expression of different protein isoforms and therefore the existence of distinct muscle fibre phenotypes is one of the main determinants of the muscle performance in vivo. The present review will first describe the mechanisms through which molecular diversity is generated and how fibre types can be identified on the basis of structural and functional characteristics. Then the molecular and functional diversity will be examined with regard to (1) the myofibrillar apparatus; (2) the sarcolemma and the sarcoplasmic reticulum; and (3) the metabolic systems devoted to producing ATP. The last section of the review will discuss the advantage that fibre diversity can offer in optimizing muscle contractile performance.
Topics: Calcium; Electrophysiology; Humans; Ion Channels; Models, Biological; Muscle Fibers, Skeletal; Muscle, Skeletal; Protein Isoforms; Temperature
PubMed: 10958931
DOI: 10.1016/s0079-6107(00)00006-7 -
The FEBS Journal Oct 2018Different forms of myosin heavy chains (MyHCs), coded by a large family of sarcomeric MYH genes, are expressed in striated muscles. The generation of specific anti-MyHC... (Review)
Review
Different forms of myosin heavy chains (MyHCs), coded by a large family of sarcomeric MYH genes, are expressed in striated muscles. The generation of specific anti-MyHC antibodies has provided a powerful tool to define the fiber types present in skeletal muscles, their functional properties, their response to conditions that affect muscle plasticity and their changes in muscle disorders. Cardiomyocyte heterogeneity has been revealed by the serendipitous observation that different MyHCs are present in atrial and ventricular myocardium and in heart conduction tissue. Developmental MyHCs present in embryonic and fetal/neonatal skeletal muscle are re-expressed during muscle regeneration and can be used to identify regenerating fibers in muscle diseases. MyHC isoforms provide cell type-specific markers to identify the signaling pathways that control muscle cell identity and are an essential reference to interpret the results of single-cell transcriptomics and proteomics.
Topics: Animals; Antibodies, Monoclonal; Gene Expression Regulation, Developmental; Humans; Muscle Fibers, Skeletal; Muscle, Skeletal; Myosin Heavy Chains; Protein Isoforms
PubMed: 29761627
DOI: 10.1111/febs.14502 -
Stem Cell Reports Apr 2017The isolation or in vitro derivation of many human cell types remains challenging and inefficient. Direct conversion of human pluripotent stem cells (hPSCs) by forced...
The isolation or in vitro derivation of many human cell types remains challenging and inefficient. Direct conversion of human pluripotent stem cells (hPSCs) by forced expression of transcription factors provides a potential alternative. However, deficient inducible gene expression in hPSCs has compromised efficiencies of forward programming approaches. We have systematically optimized inducible gene expression in hPSCs using a dual genomic safe harbor gene-targeting strategy. This approach provides a powerful platform for the generation of human cell types by forward programming. We report robust and deterministic reprogramming of hPSCs into neurons and functional skeletal myocytes. Finally, we present a forward programming strategy for rapid and highly efficient generation of human oligodendrocytes.
Topics: Cell Differentiation; Cell Line; Cellular Reprogramming; Gene Expression; Gene Targeting; Humans; Muscle Development; Muscle Fibers, Skeletal; Neurogenesis; Neurons; Oligodendroglia; Pluripotent Stem Cells; Transgenes; Up-Regulation
PubMed: 28344001
DOI: 10.1016/j.stemcr.2017.02.016 -
Journal of Applied Physiology... Aug 2017Endurance exercise training promotes numerous cellular adaptations in both cardiac myocytes and skeletal muscle fibers. For example, exercise training fosters changes in... (Review)
Review
Endurance exercise training promotes numerous cellular adaptations in both cardiac myocytes and skeletal muscle fibers. For example, exercise training fosters changes in mitochondrial function due to increased mitochondrial protein expression and accelerated mitochondrial turnover. Additionally, endurance exercise training alters the abundance of numerous cytosolic and mitochondrial proteins in both cardiac and skeletal muscle myocytes, resulting in a protective phenotype in the active fibers; this exercise-induced protection of cardiac and skeletal muscle fibers is often referred to as "exercise preconditioning." As few as 3-5 consecutive days of endurance exercise training result in a preconditioned cardiac phenotype that is sheltered against ischemia-reperfusion-induced injury. Similarly, endurance exercise training results in preconditioned skeletal muscle fibers that are resistant to a variety of stresses (e.g., heat stress, exercise-induced oxidative stress, and inactivity-induced atrophy). Many studies have probed the mechanisms responsible for exercise-induced preconditioning of cardiac and skeletal muscle fibers; these studies are important, because they provide an improved understanding of the biochemical mechanisms responsible for exercise-induced preconditioning, which has the potential to lead to innovative pharmacological therapies aimed at minimizing stress-induced injury to cardiac and skeletal muscle. This review summarizes the development of exercise-induced protection of cardiac myocytes and skeletal muscle fibers and highlights the putative mechanisms responsible for exercise-induced protection in the heart and skeletal muscles.
Topics: Animals; Exercise; Humans; Muscle Fibers, Skeletal; Muscle Proteins; Myocytes, Cardiac; Physical Conditioning, Animal
PubMed: 28572498
DOI: 10.1152/japplphysiol.00418.2017 -
The Journal of General Physiology Sep 2022JGP study reveals that adult zebrafish skeletal muscle fibers display the fastest kinetics of excitation-contraction coupling ever measured in vertebrate locomotor...
JGP study reveals that adult zebrafish skeletal muscle fibers display the fastest kinetics of excitation-contraction coupling ever measured in vertebrate locomotor muscles.
Topics: Animals; Excitation Contraction Coupling; Muscle Fibers, Skeletal; Zebrafish
PubMed: 35980354
DOI: 10.1085/jgp.202213236 -
Tissue Engineering. Part B, Reviews Oct 2014Skeletal muscle tissue engineering (SMTE) aims to repair or regenerate defective skeletal muscle tissue lost by traumatic injury, tumor ablation, or muscular disease.... (Review)
Review
Skeletal muscle tissue engineering (SMTE) aims to repair or regenerate defective skeletal muscle tissue lost by traumatic injury, tumor ablation, or muscular disease. However, two decades after the introduction of SMTE, the engineering of functional skeletal muscle in the laboratory still remains a great challenge, and numerous techniques for growing functional muscle tissues are constantly being developed. This article reviews the recent findings regarding the methodology and various technical aspects of SMTE, including cell alignment and differentiation. We describe the structure and organization of muscle and discuss the methods for myoblast alignment cultured in vitro. To better understand muscle formation and to enhance the engineering of skeletal muscle, we also address the molecular basics of myogenesis and discuss different methods to induce myoblast differentiation into myotubes. We then provide an overview of different coculture systems involving skeletal muscle cells, and highlight major applications of engineered skeletal muscle tissues. Finally, potential challenges and future research directions for SMTE are outlined.
Topics: Cell Differentiation; Coculture Techniques; Humans; Muscle Fibers, Skeletal; Myoblasts; Tissue Engineering
PubMed: 24320971
DOI: 10.1089/ten.TEB.2013.0534 -
The Journal of General Physiology Nov 2022Type 1 ryanodine receptor (RYR1) is a Ca2+ release channel in the sarcoplasmic reticulum (SR) of the skeletal muscle and plays a critical role in excitation-contraction...
Type 1 ryanodine receptor (RYR1) is a Ca2+ release channel in the sarcoplasmic reticulum (SR) of the skeletal muscle and plays a critical role in excitation-contraction coupling. Mutations in RYR1 cause severe muscle diseases, such as malignant hyperthermia, a disorder of Ca2+-induced Ca2+ release (CICR) through RYR1 from the SR. We recently reported that volatile anesthetics induce malignant hyperthermia (MH)-like episodes through enhanced CICR in heterozygous R2509C-RYR1 mice. However, the characterization of Ca2+ dynamics has yet to be investigated in skeletal muscle cells from homozygous mice because these animals die in utero. In the present study, we generated primary cultured skeletal myocytes from R2509C-RYR1 mice. No differences in cellular morphology were detected between wild type (WT) and mutant myocytes. Spontaneous Ca2+ transients and cellular contractions occurred in WT and heterozygous myocytes, but not in homozygous myocytes. Electron microscopic observation revealed that the sarcomere length was shortened to ∼1.7 µm in homozygous myocytes, as compared to ∼2.2 and ∼2.3 µm in WT and heterozygous myocytes, respectively. Consistently, the resting intracellular Ca2+ concentration was higher in homozygous myocytes than in WT or heterozygous myocytes, which may be coupled with a reduced Ca2+ concentration in the SR. Finally, using infrared laser-based microheating, we found that heterozygous myocytes showed larger heat-induced Ca2+ transients than WT myocytes. Our findings suggest that the R2509C mutation in RYR1 causes dysfunctional Ca2+ dynamics in a mutant-gene dose-dependent manner in the skeletal muscles, in turn provoking MH-like episodes and embryonic lethality in heterozygous and homozygous mice, respectively.
Topics: Animals; Calcium; Malignant Hyperthermia; Mice; Muscle Fibers, Skeletal; Muscle, Skeletal; Mutation; Ryanodine Receptor Calcium Release Channel
PubMed: 36200983
DOI: 10.1085/jgp.202213136 -
Scientific Reports Mar 2023Cell-based therapy is a major focus for treatment of stress urinary incontinence (SUI). However, derivation of primary cells requires tissue biopsies, which often have...
Cell-based therapy is a major focus for treatment of stress urinary incontinence (SUI). However, derivation of primary cells requires tissue biopsies, which often have adverse effects on patients. A recent study used human induced pluripotent stem cells (iPSC)-derived smooth muscle myocytes for urethral sphincter regeneration in rats. Here, we establish a workflow using iPSC-derived fibroblasts and skeletal myocytes for urethral tissue regeneration: (1) Cells from voided urine of women were reprogrammed into iPSC. (2) The iPSC line U1 and hESC line H9 (control) were differentiated into fibroblasts expressing FSP1, TE7, vinculin, vimentin, αSMA, fibronectin and paxillin. (3) Myogenic differentiation of U1 and H9 was induced by small molecule CHIR99021 and confirmed by protein expression of myogenic factors PAX7, MYOD, MYOG, and MF20. Striated muscle cells enriched by FACS expressed NCAM1, TITIN, DESMIN, TNNT3. (4) Human iPSC-derived fibroblasts and myocytes were engrafted into the periurethral region of RNU rats. Injected cells were labelled with ferric nanoparticles and traced by Prussian Blue stain, human-specific nuclear protein KU80, and human anti-mitochondria antibody. This workflow allows the scalable derivation, culture, and in vivo tracing of patient-specific fibroblasts and myocytes, which can be assessed in rat SUI models to regenerate urethral damages and restore continence.
Topics: Humans; Rats; Female; Animals; Induced Pluripotent Stem Cells; Fibroblasts; Cell Differentiation; Muscle, Skeletal; Muscle Fibers, Skeletal; Urinary Incontinence, Stress; Cells, Cultured
PubMed: 36959367
DOI: 10.1038/s41598-023-31780-9 -
Journal of Applied Physiology... Jun 2015
Topics: Athletes; Humans; Male; Muscle Fibers, Skeletal; Muscle, Skeletal; Running
PubMed: 25911683
DOI: 10.1152/japplphysiol.00269.2015 -
Biological & Pharmaceutical Bulletin 2011α-B-Crystallin (CryAB, gene map locus: 11q22.3-q23.1) is a member of the small heat shock protein (HSP) family, a group of proteins that prevent protein aggregation... (Review)
Review
α-B-Crystallin (CryAB, gene map locus: 11q22.3-q23.1) is a member of the small heat shock protein (HSP) family, a group of proteins that prevent protein aggregation upon exposure of a cell to heat and/or restore the biological activity of cell substrates. The missense mutation and the deletion mutation of CryAB can cause various forms of muscular disorder, including restrictive, hypertrophic, and dilated cardiomyopathies, heart failure, and skeletal muscle weakness. Collectively, these diseases constitute a rare autosomal-dominant inherited disorder called α-crystallinopathy (crystallinopathy), also known as desmin-related cardiomyopathy. The disease is a misfolded protein-related disease characterized by the formation of insoluble protein aggregates consisting of the CryAB protein in the patient's cardiomyocytes and skeletal myocytes. The details of crystallinopathy are unclear at the present time; what has been discovered concerning the disease mechanisms underlying crystallinopathy has been through experiments with genetically modified mice such as the CryAB knockout mouse and various mutant CryAB transgenic (TG) mice. Crystallinopathy can be recapitulated in TG mice by expressing the mutant CryAB Arg120Gly (R120G) protein, a causal mutation of crystallinopathy, specifically in the cardiomyocytes. CryAB R120G causes perinuclear formation of aggresomes containing preamyloid oligomer intermediates, which are wellknown as a primary toxic species in neurodegenerative disease. This suggests that crystallinopathy caused by the CryAB mutation could be considered one of the aggresomal and amyloid-related diseases. Moreover, recent findings have indicated that enhancement of HSP induction and inhibition of apoptotic cell death by mitochondrial protection may be a new therapeutic strategy for patients with crystallinopathy.
Topics: Amyloid; Animals; Apoptosis; Heat-Shock Proteins; Humans; Mitochondria; Muscle Fibers, Skeletal; Mutation; Myocytes, Cardiac; Myositis, Inclusion Body; Solubility; alpha-Crystallin B Chain
PubMed: 22040875
DOI: 10.1248/bpb.34.1653