scholarly journals Reinnervation of muscle fiber basal lamina after removal of myofibers. Differentiation of regenerating axons at original synaptic sites.

1978 ◽  
Vol 78 (1) ◽  
pp. 176-198 ◽  
Author(s):  
J R Sanes ◽  
L M Marshall ◽  
U J McMahan
Keyword(s):  
Skeletal Muscle ◽  
Basal Lamina ◽  
Muscle Fiber ◽  
Nerve Terminal ◽  
Synaptic Vesicles ◽  
Muscle Fibers ◽  
Nerve Terminals ◽  
Morphological Criteria ◽  
Histological Criteria ◽  
Active Zones

Axons regenerate to reinnervate denervated skeletal muscle fibers precisely at original synaptic sites, and they differentiate into nerve terminals where they contact muscle fibers. The aim of this study was to determine the location of factors that influence the growth and differentiation of the regenerating axons. We damaged and denervated frog muscles, causing myofibers and nerve terminals to degenerate, and then irradiated the animals to prevent regeneration of myofibers. The sheath of basal lamina (BL) that surrounds each myofiber survives these treatments, and original synaptic sites on BL can be recognized by several histological criteria after nerve terminals and muscle cells have been completely removed. Axons regenerate into the region of damage within 2 wk. They contact surviving BL almost exclusively at original synaptic sites; thus, factors that guide the axon's growth are present at synaptic sites and stably maintained outside of the myofiber. Portions of axons that contact the BL acquire active zones and accumulations of synaptic vesicles; thus by morphological criteria they differentiate into nerve terminals even though their postsynaptic targets, the myofibers, are absent. Within the terminals, the synaptic organelles line up opposite periodic specializations in the myofiber's BL, demonstrating that components associated with the BL play a role in organizing the differentiation of the nerve terminal.

scholarly journals Acetylcholine receptors in regenerating muscle accumulate at original synaptic sites in the absence of the nerve.

1979 ◽  
Vol 82 (2) ◽  
pp. 412-425 ◽  
Author(s):  
S J Burden ◽  
P B Sargent ◽  
U J McMahan
Keyword(s):  
Skeletal Muscle ◽  
Horseradish Peroxidase ◽  
Basal Lamina ◽  
Acetylcholine Receptors ◽  
Structural Organization ◽  
Neuromuscular Junctions ◽  
Muscle Fibers ◽  
Nerve Terminals ◽  
Alpha Bungarotoxin

We examined the role of nerve terminals in organizing acetylcholine receptors on regenerating skeletal-muscle fibers. When muscle fibers are damaged, they degenerate and are phagocytized, but their basal lamina sheaths survive. New myofibers form within the original basal lamina sheaths, and they become innervated precisely at the original synaptic sites on the sheaths. After denervating and damaging muscle, we allowed myofibers to regenerate but deliberately prevented reinnervation. The distribution of acetylcholine receptors on regenerating myofibers was determined by histological methods, using [125I] alpha-bungarotoxin or horseradish peroxidase-alpha-bungarotoxin; original synaptic sites on the basal lamina sheaths were marked by cholinesterase stain. By one month after damage to the muscle, the new myofibers have accumulations of acetylcholine receptors that are selectively localized to the original synaptic sites. The density of the receptors at these sites is the same as at normal neuromuscular junctions. Folds in the myofiber surface resembling junctional folds at normal neuromuscular junctions also occur at original synaptic sites in the absence of nerve terminals. Our results demonstrate that the biochemical and structural organization of the subsynaptic membrane in regenerating muscle is directed by structures that remain at synaptic sites after removal of the nerve.

scholarly journals Resveratrol regulates skeletal muscle fibers switching through the AdipoR1-AMPK-PGC-1α pathway

2019 ◽  
Vol 10 (6) ◽  
pp. 3334-3343 ◽  
Author(s):  
Qinyang Jiang ◽  
Xiaofang Cheng ◽  
Yueyue Cui ◽  
Qin Xia ◽  
Xueyu Yan ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Fiber ◽  
Fiber Type ◽  
Muscle Fibers ◽  
Underlying Mechanism ◽  
Skeletal Muscle Fiber ◽  
Muscle Fiber Type ◽  
Skeletal Muscle Fibers

This study was conducted to investigate the effect and underlying mechanism of Resveratrol (RES) in regulating skeletal muscle fiber-type switching.

scholarly journals SH3KBP1 scaffolds endoplasmic reticulum and controls skeletal myofibers architecture and integrity

2020 ◽  
Author(s):  
Alexandre Guiraud ◽  
Emilie Christin ◽  
Nathalie Couturier ◽  
Carole Kretz-Remy ◽  
Alexandre Janin ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Endoplasmic Reticulum ◽  
Muscle Fiber ◽  
Muscle Fibers ◽  
Normal Function ◽  
Pairwise Distance ◽  
Frequent Mutation ◽  
Muscular Development ◽  
T Tubules ◽  
Early Phases

AbstractThe building block of skeletal muscle is the multinucleated muscle fiber, formed by the fusion of hundreds of mononucleated precursor cells, myoblasts. In the normal course of muscle fiber development or regeneration, myonuclei are actively positioned throughout muscular development and adopt special localization in mature fibers: regular spacing along muscle fibers periphery, raising the notion of MyoNuclear Domains (MNDs). There is now growing support for a direct connection between myonuclear positioning and normal function of muscles, but how myonuclei affects muscle function remains poorly characterized.To identify new factors regulating forces applied on myonuclei in muscles fibers, we performed a siRNA screen and identified SH3KBP1 as a new factor controlling myonuclear positioning in early phases of myofibers formation. Depletion of SH3KBP1 induces a reset of MNDs establishment in mature fibers reflected by a dramatic reduction in pairwise distance between myonuclei. We show that SH3KBP1 scaffolds Endoplasmic Reticulum (ER) in myotubes that in turn controls myonuclei velocity and localization and thus myonuclear domains settings. Additionally, we show that in later phases of muscle maturation, SH3KBP1 contributes to the formation and maintenance of Sarcoplasmic Reticulum (SR) and Transverse-tubules (T-tubules). We also demonstrate that in muscle fibers, GTPase dynamin-2 (DNM2) binds to SH3 domains of SH3KBP1. Interestingly, we observed that Sh3kbp1 mRNA is up regulated in a mouse model harboring the most frequent mutation for Autosomal Dominant CentroNuclear Myopathy (AD-CNM): Dnm2+/R465W. SH3KBP1 thus appears as a compensation mechanism in this CNM model since its depletion contributes to an increase of CNM-like phenotypes (reduction of muscle fibers Cross-section Areas (CSA) and increase in slow fibers content).Altogether our results identify SH3KBP1 as a new regulator of myonuclear domains establishment in the early phase of muscle fibers formation through ER scaffolding and later in myofibers integrity through T-tubules scaffolding/maintenance.SummaryMyonuclei are actively positioned throughout muscular development. Guiraud, Christin, Couturier et al show that SH3KBP1 scaffolds the ER through Calnexin interaction and controls myonuclei motion during early steps of muscle fibers formation. Besides SH3KBP1 participates in cell fusion and T-tubules formation/maintenance in mature skeletal muscle fibers and contributes to slow-down CNM-like phenotypes.

scholarly journals LncRNAs and CircRNAs Control Myofiber-Specific Expression Profiles by Acting as CeRNAs in Mongolian Horses

2021 ◽  
Author(s):  
Tugeqin Bao ◽  
Haige Han ◽  
Ruoyang Zhao ◽  
Togtokh Mongke ◽  
Xima La ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Fiber ◽  
Enzyme Activities ◽  
Muscle Fibers ◽  
Noncoding Rnas ◽  
Gluteus Medius ◽  
Differentially Expressed ◽  
Metabolic Enzyme ◽  
Gluteus Medius Muscle ◽  
Fiber Composition

Abstract Background: The heterogeneity and plasticity of muscle fibers are essential for the athletic performance of horses, mainly at the adaption of exercises and the effect on muscle diseases. Skeletal muscle fibers can be generally distinguished by their characteristics of contraction as slow and fast type myofibers. The diversity of contractile properties and metabolism enable skeletal muscles to respond to the variable functional requirements. We investigated the muscle fiber composition and metabolic enzyme activities of splenius muscle and gluteus medius muscle from Mongolian horses. The deep RNA-seq analysis of detecting differentially expressed mRNAs, lncRNAs, circRNAs and their correlation analysis from two muscles were performed.Results: Splenius muscle and gluteus medius muscle from Mongolian horses showed a high divergence of myofiber compositions and metabolic enzyme activities. Corresponding to their phenotypic characteristics, 94 differentially expressed long noncoding RNAs and 91 differentially expressed circle RNAs were found between two muscles. The analysis results indicate multiple binding sites were detected in lncRNAs and circRNAs with myofiber-specific expressed miRNAs. Among which we found significant correlations between the above noncoding RNAs, miRNAs, their target genes, myofiber-specific developmental transcript factors, and sarcomere genes. Conclusions: We suggest that the ceRNA mechanism of myofiber-specific expressed noncoding RNAs by acting as miRNA sponges could be fine tuners in regulating skeletal muscle fiber composition and transition in horses, which will operate new protective measures of muscle disease and locomotor adaption for racehorses.

scholarly journals Histological aspects of skeletal muscle fibers splitting of C57BL/6NCrl mice

2020 ◽  
pp. 291-296 ◽  
Author(s):  
P. Makovický ◽  
P. Makovický
Keyword(s):  
Skeletal Muscle ◽  
Muscle Fiber ◽  
Skeletal Muscles ◽  
Muscle Fibers ◽  
Rectus Femoris ◽  
Skeletal Muscle Fiber ◽  
Fiber Splitting ◽  
Muscular Fiber ◽  
Skeletal Muscle Fibers ◽  
Muscle Fiber Regeneration

The objective of the current study is to present data on the splitting of skeletal muscle fibers in C57BL/6NCrl mice. Skeletal muscles (m. rectus femoris (m. quadriceps femoris)) from 500 (250 ♀ and 250 ♂) C57BL/6NCrl mice in the 16th week of life were sampled during autopsy and afterwards standardly histologically processed. Results show spontaneous skeletal muscle fiber splitting which is followed by skeletal muscle fiber regeneration. One solitary skeletal muscle fiber is split, or is in contact with few localized splitting skeletal muscle fibers. Part of the split skeletal muscular fiber is phagocytosed, but the remaining skeletal muscular fiber splits are merged into one regenerating skeletal muscle fiber. Nuclei move from the periphery to the regenerating skeletal muscle fiber center during this process. No differences were observed between female and male mice and the morphometry results document <1 % skeletal muscle fiber splitting. If skeletal muscular fibers splitting occurs 5 %> of all skeletal muscular fibers, it is suggested to describe and calculate this in the final histopathological report.

Reduced Mg2+ inhibition of Ca2+ release in muscle fibers of pigs susceptible to malignant hyperthermia

1997 ◽  
Vol 272 (1) ◽  
pp. C203-C211 ◽  
Author(s):  
V. J. Owen ◽  
N. L. Taske ◽  
G. D. Lamb
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Malignant Hyperthermia ◽  
Ryanodine Receptor ◽  
Muscle Fiber ◽  
Muscle Fibers ◽  
Inhibitory Effect ◽  
Fiber Bundles ◽  
Force Response ◽  
Skeletal Muscle Fibers

The inhibitory effect of myoplasmic Mg2+ on Ca2+ release from the sarcoplasmic reticulum (SR) was examined in mechanically skinned skeletal muscle fibers from pigs of different ryanodine-receptor (RyR) genotypes. In fibers from pigs homozygous for the normal RyR allele, the free Mg2+ concentration ([Mg2+]) had to be lowered from the normal resting level of 1 to approximately 0.1 mM to induce Ca2+ release and a force response. Fibers from pigs heterozygous or homozygous for the RyR allele associated with malignant hyperthermia (MH) needed only a smaller reduction in free [Mg2+] to induce Ca2+ release (reduction to 0.1-0.2 and > or = 0.2 mM, respectively). Dantrolene (20 microM) counteracted the effect of this reduced Mg2+ inhibition in MH muscle. The response of muscle fiber bundles to the caffeine-halothane contracture test in the three genotypes correlated well with the responsiveness of single fibers to reduced [Mg2+]. Thus the abnormal responsiveness of MH muscle to various stimuli may largely result from the reduced ability of myoplasmic Mg2+ to inhibit Ca2+ release from the SR.

Degenerative changes in the muscle fibers of Manduca sexta during metamorphosis

1992 ◽  
Vol 167 (1) ◽  
pp. 91-117 ◽  
Author(s):  
M. B. Rheuben
Keyword(s):  
Manduca Sexta ◽  
Basal Lamina ◽  
Muscle Fiber ◽  
Structural Changes ◽  
Muscle Fibers ◽  
Resting Potential ◽  
Ultrastructural Changes ◽  
Intimate Contact ◽  
Cross Sectional ◽  
Dense Granules

The ultrastructural changes associated with the early stages of degeneration of the larval mesothoracic muscle fibers of Manduca sexta were examined during the prepupal period and on the first day after ecdysis. Over this 5 day period, the muscle fibers decrease in cross-sectional area but increase in apparent surface area compared to the dimensions of early fifth-instar fibers. Large numbers of electron-dense granules or droplets are formed and extruded from the muscle cytoplasm into the hemolymph; this process may account for some of the decrease in muscle fiber mass and may represent a developmental mechanism for recycling nutrients. As the fibers shrink, the thick basal lamina is thrown into folds. Phagocytic hemocytes (granulocytes) congregate in clusters over the surface of the degenerating fibers and appear to remove specifically the basal lamina. The timely removal of the thick larval basal lamina may be essential for subsequent fusion of myoblasts to the residual larval myofibers. The contractile elements within the degenerating muscle fibers become disorganized but are not dysfunctional at the end of the first 12 h after the pupal ecdysis. Tracheoles withdraw from intimate contact with each muscle fiber in its clefts and T-tubules and associate in groups adjacent to it. Mitochondria appear to be degenerating. These structural changes are concurrent with a previously observed decline in resting potential and suggest that a significant change in the electrical properties of the muscle fibers should be expected as well.

Abstract 478: Connexin-43 Reduction Rescues Cardiac and Skeletal Muscle Pathology in a Novel Mouse Model of Duchenne Muscular Dystrophy Symptomatic Carriers

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Julie Nouet ◽  
Eric Himelman ◽  
Diego Fraidenraich
Keyword(s):  
Skeletal Muscle ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Mouse Model ◽  
Muscle Fiber ◽  
Connexin 43 ◽  
Muscle Fibers ◽  
Skeletal Muscle Fiber ◽  
Muscle Pathology ◽  
Female Carriers

Duchenne muscular dystrophy (DMD) and its associated cardiomyopathy manifest in 8-10% of all female carriers however research remains male-centric. Although underrepresented, symptomatic females face the risk of cardiac, respiratory, and skeletal muscle problems. Basic research and clinical trials exclude female carriers therefore developments in treatment expose females to unknown safety and efficacy issues. The bottleneck is largely due to the absence of a faithful mouse model. To generate a mouse model, we injected mdx embryonic stem cells (ESCs) into wild-type (WT) blastocysts ( mdx /WT chimera). The cardiac and skeletal muscle phenotype recapitulates the same generated as a consequence of x-inactivation in human manifesting female patients. In the heart, mdx /WT chimeras develop fibrotic cardiomyopathy. In the skeletal muscle, we found evidence of fibrosis, inflammation and muscle weakness. We found that Connexin-43 (Cx43), the primary gap junctional protein in the heart, was pathologically enhanced and remodeled in mdx /WT chimeras. Cx43 was also enhanced in the dystrophic skeletal muscle. Genetic reduction of Cx43-copy number protected mdx /WT chimeras from cardiac and skeletal muscle fiber damage. The latter result was unexpected because Cx43 is not expressed in mature muscle fibers. Upon further investigation, Cx43 was localized to the mononuclear cells invading the interstitial space between dystrophic skeletal muscle fibers. Pathologically enhanced activity of Cx43 in mdx FACS-macrophages was observed via ethidium bromide uptake and the Cx43 hemichannel peptide mimetic, Gap19, inhibited Cx43 function in a dose-dependent manner. Because an excess of Cx43 has been associated with cell death, we believe that Cx43 reduction in invading mdx macrophages benefits the skeletal muscle of understudied DMD carriers, perhaps by a paracrine mechanism involving macrophage-skeletal muscle fiber communication.

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