Fiber type conversion alters inactivation of voltage-dependent sodium currents in murine C2C12skeletal muscle cells

2004 ◽  
Vol 287 (2) ◽  
pp. C270-C280 ◽  
Author(s):  
Eva Zebedin ◽  
Walter Sandtner ◽  
Stefan Galler ◽  
Julia Szendroedi ◽  
Herwig Just ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fiber Type ◽  
Muscle Fibers ◽  
Muscle Cells ◽  
The Body ◽  
Skeletal Muscle Cells ◽  
Prolonged Treatment ◽  
Type Conversion ◽  
Electrophysiological Properties ◽  
Slow Fiber

Each skeletal muscle of the body contains a unique composition of “fast” and “slow” muscle fibers, each of which is specialized for certain challenges. This composition is not static, and the muscle fibers are capable of adapting their molecular composition by altered gene expression (i.e., fiber type conversion). Whereas changes in the expression of contractile proteins and metabolic enzymes in the course of fiber type conversion are well described, little is known about possible adaptations in the electrophysiological properties of skeletal muscle cells. Such adaptations may involve changes in the expression and/or function of ion channels. In this study, we investigated the effects of fast-to-slow fiber type conversion on currents via voltage-gated Na+channels in the C2C12murine skeletal muscle cell line. Prolonged treatment of cells with 25 nM of the Ca2+ionophore A-23187 caused a significant shift in myosin heavy chain isoform expression from the fast toward the slow isoform, indicating fast-to-slow fiber type conversion. Moreover, Na+current inactivation was significantly altered. Slow inactivation less strongly inhibited the Na+currents of fast-to-slow fiber type-converted cells. Compared with control cells, the Na+currents of converted cells were more resistant to block by tetrodotoxin, suggesting enhanced relative expression of the cardiac Na+channel isoform Nav1.5 compared with the skeletal muscle isoform Nav1.4. These results imply that fast-to-slow fiber type conversion of skeletal muscle cells involves functional adaptation of their electrophysiological properties.

scholarly journals Single-nucleus transcriptomics reveals functional compartmentalization in syncytial skeletal muscle cells

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Minchul Kim ◽  
Vedran Franke ◽  
Bettina Brandt ◽  
Elijah D. Lowenstein ◽  
Verena Schöwel ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mouse Model ◽  
Fiber Type ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Isolated Nuclei ◽  
Nuclear Compartments ◽  
Transcriptional Dynamics ◽  
Single Nucleus ◽  
Functional Analyses

AbstractSyncytial skeletal muscle cells contain hundreds of nuclei in a shared cytoplasm. We investigated nuclear heterogeneity and transcriptional dynamics in the uninjured and regenerating muscle using single-nucleus RNA-sequencing (snRNAseq) of isolated nuclei from muscle fibers. This revealed distinct nuclear subtypes unrelated to fiber type diversity, previously unknown subtypes as well as the expected ones at the neuromuscular and myotendinous junctions. In fibers of the Mdx dystrophy mouse model, distinct subtypes emerged, among them nuclei expressing a repair signature that were also abundant in the muscle of dystrophy patients, and a nuclear population associated with necrotic fibers. Finally, modifications of our approach revealed the compartmentalization in the rare and specialized muscle spindle. Our data identifies nuclear compartments of the myofiber and defines a molecular roadmap for their functional analyses; the data can be freely explored on the MyoExplorer server (https://shiny.mdc-berlin.de/MyoExplorer/).

Calcium-independent phospholipase A2 modulates cytosolic oxidant activity and contractile function in murine skeletal muscle cells

2006 ◽  
Vol 100 (2) ◽  
pp. 399-405 ◽  
Author(s):  
Ming C. Gong ◽  
Sandrine Arbogast ◽  
Zhenheng Guo ◽  
Jeremy Mathenia ◽  
Wen Su ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mammalian Cells ◽  
Contractile Function ◽  
Muscle Fibers ◽  
Force Production ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Force Frequency ◽  
Striated Muscles

Phospholipase A2 (PLA2) activity supports production of reactive oxygen species (ROS) by mammalian cells. In skeletal muscle, endogenous ROS modulate the force of muscle contraction. We tested the hypothesis that skeletal muscle cells constitutively express the calcium-independent PLA2 (iPLA2) isoform and that iPLA2 modulates both cytosolic oxidant activity and contractile function. Experiments utilized differentiated C2C12 myotubes and a panel of striated muscles isolated from adult mice. Muscle preparations were processed for measurement of mRNA by real-time PCR, protein by immunoblot, cytosolic oxidant activity by the dichlorofluorescein oxidation assay, and contractile function by in vitro testing. We found that iPLA2 was constitutively expressed by all muscles tested (myotubes, diaphragm, soleus, extensor digitorum longus, gastrocnemius, heart) and that mRNA and protein levels were generally similar among muscles. Selective iPLA2 blockade by use of bromoenol lactone (10 μM) decreased cytosolic oxidant activity in myotubes and intact soleus muscle fibers. iPLA2 blockade also inhibited contractile function of unfatigued soleus muscles, shifting the force-frequency relationship rightward and depressing force production during acute fatigue. Each of these changes could be reproduced by selective depletion of superoxide anions using superoxide dismutase (1 kU/ml). These findings suggest that constitutively expressed iPLA2 modulates oxidant activity in skeletal muscle fibers by supporting ROS production, thereby influencing contractile properties and fatigue characteristics.

C2C12 skeletal muscle cells adopt cardiac-like sodium current properties in a cardiac cell environment

2007 ◽  
Vol 292 (1) ◽  
pp. H439-H450 ◽  
Author(s):  
Eva Zebedin ◽  
Markus Mille ◽  
Maria Speiser ◽  
Touran Zarrabi ◽  
Walter Sandtner ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Sodium Channel ◽  
Sodium Current ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Cardiac Cell ◽  
Sodium Currents ◽  
Current Function ◽  
Electrophysiological Properties ◽  
Cardiac Sodium Channel

Intracardiac transplantation of undifferentiated skeletal muscle cells (myoblasts) has emerged as a promising therapy for myocardial infarct repair and is already undergoing clinical trials. The fact that cells originating from skeletal muscle have different electrophysiological properties than cardiomyocytes, however, may considerably limit the success of this therapy and, in addition, cause side effects. Indeed, a major problem observed after myoblast transplantation is the occurrence of ventricular arrhythmias. The most often transient nature of these arrhythmias may suggest that, once transplanted into cardiac tissue, skeletal muscle cells adopt more cardiac-like electrophysiological properties. To test whether a cardiac cell environment can indeed modify electrophysiological parameters of skeletal muscle cells, we treated mouse C2C12 myocytes with medium preconditioned by primary cardiocytes and compared their functional sodium current properties with those of control cells. We found this treatment to significantly alter the activation and inactivation properties of sodium currents from “skeletal muscle” to more “cardiac”-like ones. Sodium currents of cardiac-conditioned cells showed a reduced sensitivity to block by tetrodotoxin. These findings and reverse transcription PCR experiments suggest that an upregulation of the expression of the cardiac sodium channel isoform Nav1.5 versus the skeletal muscle isoform Nav1.4 is responsible for the observed changes in sodium current function. We conclude that cardiomyocytes alter sodium channel isoform expression of skeletal muscle cells via a paracrine mechanism. Thereby, skeletal muscle cells with more cardiac-like sodium current properties are generated.

Factors Controlling Movement of Skeletal Muscles

Leonardo ◽  
2015 ◽  
Vol 48 (3) ◽  
pp. 270-271
Author(s):  
Miranda D. Grounds
Keyword(s):  
Skeletal Muscle ◽  
Extracellular Matrix ◽  
Cell Membrane ◽  
Skeletal Muscles ◽  
Muscle Cells ◽  
The Body ◽  
Skeletal Muscle Cells ◽  
3 Dimensional

The contraction of specialized skeletal muscle cells results in classic movements of bones and other parts of the body that are vital for life. There is exquisite control over the movement of diverse types of muscles. This paper indicates the way in which skeletal muscles (myofibres) are formed; then factors that contribute to generating the movement are outlined: these include the nerve, sarcomeres, cytoskeleton, cell membrane and the extracellular matrix. The factors controlling the movement of mature myofibres in 3-dimensional tissues in vivo are vastly more complex than for tissue cultured immature muscle cells in an artificial in vitro environment.

scholarly journals Activity-dependent and -independent nuclear fluxes of HDAC4 mediated by different kinases in adult skeletal muscle

2005 ◽  
Vol 168 (6) ◽  
pp. 887-897 ◽  
Author(s):  
Yewei Liu ◽  
William R. Randall ◽  
Martin F. Schneider
Keyword(s):  
Skeletal Muscle ◽  
Histone Deacetylases ◽  
Fiber Type ◽  
Muscle Fibers ◽  
Adult Skeletal Muscle ◽  
Slow Fiber ◽  
Fast Fiber ◽  
Dependent Protein ◽  
Nuclear Levels ◽  
Activity Dependent

Class II histone deacetylases (HDACs) may decrease slow muscle fiber gene expression by repressing myogenic transcription factor myocyte enhancer factor 2 (MEF2). Here, we show that repetitive slow fiber type electrical stimulation, but not fast fiber type stimulation, caused HDAC4-GFP, but not HDAC5-GFP, to translocate from the nucleus to the cytoplasm in cultured adult skeletal muscle fibers. HDAC4-GFP translocation was blocked by calmodulin-dependent protein kinase (CaMK) inhibitor KN-62. Slow fiber type stimulation increased MEF2 transcriptional activity, nuclear Ca2+ concentration, and nuclear levels of activated CaMKII, but not total nuclear CaMKII or CaM-YFP. Thus, calcium transients for slow, but not fast, fiber stimulation patterns appear to provide sufficient Ca2+-dependent activation of nuclear CaMKII to result in net nuclear efflux of HDAC4. Nucleocytoplasmic shuttling of HDAC4-GFP in unstimulated resting fibers was not altered by KN-62, but was blocked by staurosporine, indicating that different kinases underlie nuclear efflux of HDAC4 in resting and stimulated muscle fibers.

scholarly journals Gene regulation mediating fiber-type transformation in skeletal muscle cells is partly glucose- and ChREBP-dependent

2011 ◽  
Vol 1813 (3) ◽  
pp. 377-389 ◽  
Author(s):  
Nina Hanke ◽  
Renate J. Scheibe ◽  
Georgi Manukjan ◽  
David Ewers ◽  
Patrick K. Umeda ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Gene Regulation ◽  
Fiber Type ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Type Transformation

scholarly journals Glucocorticoid Receptor Alpha Targets SLC2A4 to Regulate Protein Synthesis and Breakdown in Porcine Skeletal Muscle Cells

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 721
Author(s):  
Xiao-Li Du ◽  
Wei-Jing Xu ◽  
Jia-Li Shi ◽  
Kai Guo ◽  
Chang-Tong Guo ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Cells ◽  
The Body ◽  
Skeletal Muscle Cells ◽  
Luciferase Reporter ◽  
Protein Breakdown ◽  
Reporter Assays ◽  
Solute Carrier ◽  
Regulate Protein ◽  
Hpa Axis Activity

In the presence of stress, the hypothalamic-pituitary-adrenal (HPA) axis activity can be enhanced to promote the secretion of a large amount of glucocorticoids (GCs), which play an important role in the anabolism and catabolism of skeletal muscle. When the endogenous and exogenous glucocorticoids are deficient or excessive, the body will produce stress-related resistance and change the protein metabolism. In this study, we investigated the effect of GC receptor GRα on protein breakdown and synthesis in porcine skeletal muscle cells (PSCs). Overexpression of GRα was shown to increase the expression of protein degradation-related genes, while knockdown of GRα decreased the expression of these genes. Additionally, we found a relationship between GRα and solute carrier family 2 member 4 (SLC2A4), SLC2A4 expression level increases when stress occurs, suggesting that increasing SLC2A4 expression can partially alleviate stress-induced damage, and we found that there is a combination between them via luciferase reporter assays, which still needs to be confirmed in further studies.

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