Ion Channels and Transporters in Muscle Cell Differentiation

Chen, Lingye; Nia, Fatemeh Hassani; Stauber, Tobias

doi:10.3390/ijms222413615

Cited by 15 publications

(8 citation statements)

References 152 publications

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“…Considering the time course of expression of Scn5a , its overexpression in DYS myocytes at D11 could be considered a sign of a delayed or impaired maturation in this cell line. These data would support previous findings showing that voltage‐gated sodium channels, essential for the excitability of skeletal muscle, 55 can also play an important role in muscle cell differentiation and possibly in the myogenic process 56,57 …”

Section: Discussionsupporting

confidence: 91%

“…These data would support previous findings showing that voltage-gated sodium channels, essential for the excitability of skeletal muscle, 55 can also play an important role in muscle cell differentiation and possibly in the myogenic process. 56,57 Importantly, Na v 1.4 channels, as well as Na v 1.5, are known to indirectly interact with dystrophin through the dystrophin-associated protein complex (DAPC). This suggests that the lack of dystrophin, by disrupting this interaction, 21 may alter the expression and functioning of those channels.…”

Section: Inward and Outward Currentsmentioning

confidence: 99%

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Ion channels as biomarkers of altered myogenesis in myofiber precursors of Duchenne muscular dystrophy

Cerchiara,

Imbrici,

Quarta

et al. 2024

Annals of the New York Academy of Sciences

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Myogenesis is essential for skeletal muscle formation, growth, and regeneration and can be altered in Duchenne muscular dystrophy (DMD), an X‐linked disorder due to the absence of the cytoskeletal protein dystrophin. Ion channels play a pivotal role in muscle differentiation and interact with the dystrophin complex. To investigate ion channel involvement in myogenesis in dystrophic settings, we performed electrophysiological characterization of two immortalized mouse cell lines, wild‐type (WT) H2K‐2B4 and the dystrophic (DYS) H2K‐SF1, and measured gene expression of differentiation markers and ion channels. Inward and outward currents/density increased as differentiation progressed in both WT and DYS cells. However, day‐11 DYS cells showed higher (27%) inward current density with an increased expression ratio of Scn5a/Scn4a and decreased (48%) barium‐sensitive outward current compared to WT. Furthermore, day‐11 DYS cells showed more positive resting membrane potential (+10 mV) and lower membrane capacitance (50%) compared to WT. DYS cells also had reduced Myog and Myf5 expression at days 6 and 11. Overall, ion channel profile and myogenesis appeared altered in DYS cells. These results are a first step in validating ion channels as potential drug targets to ameliorate muscle degeneration in DMD settings and as differentiation biomarkers in innovative platforms.

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Section: Discussionsupporting

confidence: 91%

Section: Inward and Outward Currentsmentioning

confidence: 99%

Ion channels as biomarkers of altered myogenesis in myofiber precursors of Duchenne muscular dystrophy

Cerchiara,

Imbrici,

Quarta

et al. 2024

Annals of the New York Academy of Sciences

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“…Research implicates transmembrane ion transporters in tissue and organ development ( Levin 2014 ; Liebeskind et al 2015 ; Hegedus et al 2020 ; Chen et al 2021 ). Given the ancient origin of the vast majority of tandem duplicated exon substitution events ( Gómez et al 2021 ), the coincidence of tandem duplicated exon substitution events in orthologous vertebrate and invertebrate gene families, the extraordinarily high levels of tissue specificity in proteomics experiments, and the enrichment in tissue-specific functional terms, it is not too much of a stretch to hypothesize that tandem duplicated exon substitution events may have played important roles in the evolution of metazoan organs and tissues.…”

Section: Discussionmentioning

confidence: 99%

Origins and Evolution of Human Tandem Duplicated Exon Substitution Events

Martínez-Gómez

Cerdán-Vélez

Abascal

et al. 2022

Genome Biology and Evolution

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The mutually exclusive splicing of tandem duplicated exons produces protein isoforms that are identical save for a homologous region that allows for the fine tuning of protein function. Tandem duplicated exon substitution events are rare, yet highly important alternative splicing events. Most events are ancient, their isoforms are highly expressed, and they have significantly more pathogenic mutations than other splice event. Here we analysed the physicochemical properties and functional roles of the homologous polypeptide regions produced by the 236 tandem duplicated exon substitutions annotated in the human gene set. We find that most important structural and functional residues in these homologous regions are maintained and that most changes are conservative rather than drastic. Three quarters of the isoforms produced from tandem duplicated exon substitution events are tissue specific, particularly in nervous and cardiac tissues, and tandem duplicated exon substitution events are enriched in functional terms related to structures in the brain and skeletal muscle. We find considerable evidence for the convergent evolution of tandem duplicated exon substitution events in vertebrates, arthropods and nematodes. Twelve human gene families have orthologues with tandem duplicated exon substitution events in both Drosophila melanogaster and Caenorhabditis elegans. Six of these gene families are ion transporters, suggesting that tandem exon duplication in genes that control the flow of ions into the cell has an adaptive benefit. The ancient origins, the strong indications of tissue-specific functions, and the evidence of convergent evolution suggest that these events may have played important roles in the evolution of animal tissues and organs.

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“…The RMP in myoblasts becomes hyperpolarised as a prerequisite for myoblast fusion via the sequential expression of two different potassium channels. Initial events during myogenic differentiation are the activation of ether-à-go-go (EAG) K + channels and Kir2.1 inward-rectifier K + channels [ 103 ].…”

Section: Ion Channels Involved In Progenitor Cell Differentiationmentioning

confidence: 99%

“…Besides the contributors of hyperpolarisation, several types of other ion channels, including ERG channels, SOCE channels, and volume-regulated anion channels (VRACs), proved to influence the RMP of fusion-competent myoblasts. The most-recent results suggest that the fusion-related hyperpolarisation is to set the RMP of myoblasts in a range that allows Ca 2+ to enter through 1H T-type Ca 2+ channels, causing a significant increase in the resting intracellular Ca 2+ concentration, which activates numerous signalling cascades [ 103 , 104 ].…”

Section: Ion Channels Involved In Progenitor Cell Differentiationmentioning

confidence: 99%

Ca2+-Activated K+ Channels in Progenitor Cells of Musculoskeletal Tissues: A Narrative Review

Takács

Kovács

Ebeid

et al. 2023

IJMS

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Musculoskeletal disorders represent one of the main causes of disability worldwide, and their prevalence is predicted to increase in the coming decades. Stem cell therapy may be a promising option for the treatment of some of the musculoskeletal diseases. Although significant progress has been made in musculoskeletal stem cell research, osteoarthritis, the most-common musculoskeletal disorder, still lacks curative treatment. To fine-tune stem-cell-based therapy, it is necessary to focus on the underlying biological mechanisms. Ion channels and the bioelectric signals they generate control the proliferation, differentiation, and migration of musculoskeletal progenitor cells. Calcium- and voltage-activated potassium (KCa) channels are key players in cell physiology in cells of the musculoskeletal system. This review article focused on the big conductance (BK) KCa channels. The regulatory function of BK channels requires interactions with diverse sets of proteins that have different functions in tissue-resident stem cells. In this narrative review article, we discuss the main ion channels of musculoskeletal stem cells, with a focus on calcium-dependent potassium channels, especially on the large conductance BK channel. We review their expression and function in progenitor cell proliferation, differentiation, and migration and highlight gaps in current knowledge on their involvement in musculoskeletal diseases.

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Ion Channels and Transporters in Muscle Cell Differentiation

Cited by 15 publications

References 152 publications

Ion channels as biomarkers of altered myogenesis in myofiber precursors of Duchenne muscular dystrophy

Ion channels as biomarkers of altered myogenesis in myofiber precursors of Duchenne muscular dystrophy

Origins and Evolution of Human Tandem Duplicated Exon Substitution Events

Ca2+-Activated K+ Channels in Progenitor Cells of Musculoskeletal Tissues: A Narrative Review

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