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

Dóra Bodnár, Nikolett Geyer, Olga Ruzsnavszky, Tamás Oláh, Bence Hegyi, Mónika Sztretye, János Fodor, Beatrix Dienes, Ágnes Balogh, Z. Papp, László Szabó, Géza Müller, L. Csernoch, P. Szentesi

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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 the myostatin 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 ΔF/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.

Original languageEnglish
Pages (from-to)1353-1365
Number of pages13
JournalJournal of Physiology
Volume592
Issue number6
DOIs
Publication statusPublished - Mar 15 2014

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Myostatin
Calcium Signaling
Calcium
Mutation
Genes
Sarcoplasmic Reticulum
Muscles
Excitation Contraction Coupling
Transforming Growth Factors
Inbred C57BL Mouse
Running
Skeletal Muscle
Growth

ASJC Scopus subject areas

  • Physiology
  • Medicine(all)

Cite this

Hypermuscular mice with mutation in the myostatin gene display altered calcium signalling. / Bodnár, Dóra; Geyer, Nikolett; Ruzsnavszky, Olga; Oláh, Tamás; Hegyi, Bence; Sztretye, Mónika; Fodor, János; Dienes, Beatrix; Balogh, Ágnes; Papp, Z.; Szabó, László; Müller, Géza; Csernoch, L.; Szentesi, P.

In: Journal of Physiology, Vol. 592, No. 6, 15.03.2014, p. 1353-1365.

Research output: Contribution to journalArticle

Bodnár, D, Geyer, N, Ruzsnavszky, O, Oláh, T, Hegyi, B, Sztretye, M, Fodor, J, Dienes, B, Balogh, Á, Papp, Z, Szabó, L, Müller, G, Csernoch, L & Szentesi, P 2014, 'Hypermuscular mice with mutation in the myostatin gene display altered calcium signalling', Journal of Physiology, vol. 592, no. 6, pp. 1353-1365. https://doi.org/10.1113/jphysiol.2013.261958
Bodnár D, Geyer N, Ruzsnavszky O, Oláh T, Hegyi B, Sztretye M et al. Hypermuscular mice with mutation in the myostatin gene display altered calcium signalling. Journal of Physiology. 2014 Mar 15;592(6):1353-1365. https://doi.org/10.1113/jphysiol.2013.261958
Bodnár, Dóra ; Geyer, Nikolett ; Ruzsnavszky, Olga ; Oláh, Tamás ; Hegyi, Bence ; Sztretye, Mónika ; Fodor, János ; Dienes, Beatrix ; Balogh, Ágnes ; Papp, Z. ; Szabó, László ; Müller, Géza ; Csernoch, L. ; Szentesi, P. / Hypermuscular mice with mutation in the myostatin gene display altered calcium signalling. In: Journal of Physiology. 2014 ; Vol. 592, No. 6. pp. 1353-1365.
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