Hypermuscular mice with mutation in the myostatin gene display altered calcium signalling

Bodnár, Dóra and Geyer, Nikolett and Ruzsnavszky, Olga and Oláh, Tamás and Hegyi, Bence and Sztretye, Mónika and Fodor, János and Dienes, Beatrix and Balogh, Ágnes and Papp, Zoltán and Szabó, László and Müller, Géza and Csernoch, László and Szentesi, Péter (2014) Hypermuscular mice with mutation in the myostatin gene display altered calcium signalling. JOURNAL OF PHYSIOLOGY - LONDON. pp. 1353-1365. ISSN 0022-3751

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Myostatin, a member of the transforming growth factor β family, is a potent negative regulator of skeletal muscle growth, as myostatin-deficient mice show a great increase in muscle mass. Yet the physical performance of these animals is reduced. As an explanation for this, alterations in the steps in excitation–contraction coupling were hypothesized and tested for in mice with the 12 bp deletion in the propeptide region of themyostatin precursor (MstnCmpt-dl1Abc or Cmpt). In voluntary wheel running, control C57BL/6 mice performed better than the mutant animals in both maximal speed and total distance covered. Despite the previously described lower specific force of Cmpt animals, the pCa–force relationship, determined on chemically permeabilized fibre segments, did not show any significant difference between the two mouse strains.While resting intracellular Ca2+ concentration ([Ca2+]i)measured on single intact flexor digitorum brevis (FDB) muscle fibres using Fura-2 AM was similar to control (72.0 ± 1.7 vs. 78.1 ± 2.9 nM, n = 38 and 45), the amplitude of KCl-evoked calcium transients was smaller (360 ± 49 vs. 222 ± 45 nM, n = 22) in the mutant strain. Similar results were obtained using tetanic stimulation and Rhod-2 AM, which gave calcium transients that were smaller (2.42±0.11 vs. 2.06 ± 0.10 �F/F0, n = 14 and 13, respectively) on Cmpt mice. Sarcoplasmic reticulum (SR) calcium release flux calculated from these transients showed a reduced peak (23.7 ± 3.0 vs. 15.8 ± 2.1 mMs−1) and steady level (5.7 ± 0.7 vs. 3.7 ± 0.5 mM s−1) with no change in the peak-to-steady ratio. The amplitude and spatial spread of calcium release events detected on permeabilized FDB fibres were also significantly smaller in mutant mice. These results suggest that reduced SR calcium release underlies the reduced muscle force in Cmpt animals

Item Type: Article
Subjects: Q Science / természettudomány > QP Physiology / élettan
Depositing User: Dr János Fodor
Date Deposited: 25 Sep 2015 16:18
Last Modified: 04 Apr 2023 11:09

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