20.500.12556/DiRROS-14128 Neuromuscular junction instability and altered intracellular calcium handling as early determinants of force loss during unloading in humans 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. Ca2+ dynamics muscle atrophy neuromuscular junction instability sarcoplasmic reticulum single fibre atrophy single fibre contractile impairment unloading Ca2+ dinamika mišičnoskeletni sistem mišice mišična atrofija sarkoplazemski retikulum true false true Angleški jezik Ni določen © 2021 The Authors Neznano 2021-06-16 08:53:23 2021-06-16 08:53:26 2022-08-19 03:39:09 0000-00-00 00:00:00 2021 0 0 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; str. 3037-3061 iss. 12 Vol. 599 Jun. 2021 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 612.74 1469-7793 10.1113/JP281365 64735747 ZRSKP_Monti_Elena_i2021.pdf ZRSKP_Monti_Elena_i2021.pdf 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. 1 6F943C20D4E806A13232B11641601867 c3a3b9516a066539c9cbf5716aa8878bfe563cbe076d196785a70ca85ee4c08b 97462282-17b6-11ed-b6b8-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=17525 https://physoc.onlinelibrary.wiley.com/doi/10.1113/JP281365 1 https://dirros.openscience.si/Dokument.php?lang=slv&id=17524 https://doi.org/10.1113/JP281365 1 https://dirros.openscience.si/Dokument.php?lang=slv&id=20237 Znanstveno-raziskovalno središče Koper / Centro di Ricerche Scientifiche Capodistria 0 0 0