| Title: | Neuromuscular junction instability and altered intracellular calcium handling as early determinants of force loss during unloading in humans |
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| Authors: | ID Monti, Elena (Author)
ID Reggiani, Carlo (Author)
ID Franchi, Martino V. (Author)
ID Toniolo, Luana (Author)
ID Sandri, Marco (Author)
ID Armani, Andrea (Author)
ID Zampieri, Sandra (Author)
ID Šimunič, Boštjan (Author)
ID Pišot, Rado (Author)
ID Narici, Marco Vicenzo (Author) |
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| Files: |  PDF - Presentation file, download (3,39 MB)
MD5: 6F943C20D4E806A13232B11641601867
Description: This is an open access article under the terms of the Creative Commons Attribution-Non Commercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
 URL - Source URL, visit https://physoc.onlinelibrary.wiley.com/doi/10.1113/JP281365
URL - Source URL, visit https://doi.org/10.1113/JP281365
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| Language: | English |
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| Typology: | 1.01 - Original Scientific Article |
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| Organization: |  ZRS Koper - Science and Research Centre Koper
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| Abstract: | Unloading induces rapid skeletal muscle atrophy and functional decline. Importantly, force is lost at a much higher rate than muscle mass. We aimed to investigate the early determinants of the disproportionate loss of force compared to that of muscle mass in response to unloading. Ten young participants underwent 10 days of bed rest (BR). At baseline (BR0) and at 10 days (BR10), quadriceps femoris (QF) volume (VOL) and isometric maximum voluntary contraction (MVC) were assessed. At BR0 and BR10 blood samples and biopsies of vastus lateralis (VL) muscle were collected. Neuromuscular junction (NMJ) stability and myofibre innervation status were assessed, together with single fibre mechanical properties and sarcoplasmic reticulum (SR) calcium handling. From BR0 to BR10, QFVOL and MVC decreased by 5.2% (P = 0.003) and 14.3% (P < 0.001), respectively. Initial and partial denervation was detected from increased neural cell adhesion molecule (NCAM)-positive myofibres at BR10 compared with BR0 (+3.4%, P = 0.016). NMJ instability was further inferred from increased C-terminal agrin fragment concentration in serum (+19.2% at BR10, P = 0.031). Fast fibre cross-sectional area (CSA) showed a trend to decrease by 15% (P = 0.055) at BR10, while single fibre maximal tension (force/CSA) was unchanged. However, at BR10 SR Ca2+ release in response to caffeine decreased by 35.1% (P < 0.002) and 30.2% (P < 0.001) in fast and slow fibres, respectively, pointing to an impaired excitation%contraction coupling. These findings support the view that the early onset of NMJ instability and impairment in SR function are eligible mechanisms contributing to the greater decline in muscle force than in muscle size during unloading. |
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| Keywords: | Ca2+ dynamics, muscle atrophy, neuromuscular junction instability, sarcoplasmic reticulum, single fibre atrophy, single fibre contractile impairment, unloading |
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| Publication status: | Published |
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| Publication version: | Version of Record |
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| Year of publishing: | 2021 |
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| Number of pages: | str. 3037-3061 |
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| Numbering: | Vol. 599 , iss. 12 |
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| PID: | 20.500.12556/DiRROS-14128  |
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| UDC: | 612.74 |
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| ISSN on article: | 1469-7793 |
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| DOI: | 10.1113/JP281365 |
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| COBISS.SI-ID: | 64735747 |
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| Copyright: | © 2021 The Authors |
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| Note: | Nasl. z nasl. zaslona;
Opis vira z dne 26. 5. 2021;
Soavtorji: Elena Monti, Carlo Reggiani, Martino V. Franchi, Luana Toniolo, Marco Sandri, Andrea Armani, Sandra Zampieri, Emiliana Giacomello, Fabio Sarto, Giuseppe Sirago, Marta Murgia, Leonardo Nogara, Lorenzo Marcucci, Stefano Ciciliot, Boštjan Šimunic, Rado Pišot and Marco V. Narici;
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| Publication date in DiRROS: | 16.06.2021 |
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| Views: | 1095 |
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| Downloads: | 1079 |
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