Restricting calcium currents is required for correct fiber type specification in skeletal muscle

Nasreen Sultana, Beatrix Dienes, Ariane Benedetti, Petronel Tuluc, P. Szentesi, Monika Sztretye, Johannes Rainer, Michael W. Hess, Christoph Schwarzer, Gerald J. Obermair, L. Csernoch, Bernhard E. Flucher

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Skeletal muscle excitation-contraction (EC) coupling is independent of calcium influx. In fact, alternative splicing of the voltage-gated calcium channel CaV1.1 actively suppresses calcium currents in mature muscle. Whether this is necessary for normal development and function of muscle is not known. However, splicing defects that cause aberrant expression of the calcium-conducting developmental CaV1.1e splice variant correlate with muscle weakness in myotonic dystrophy. Here, we deleted CaV1.1 (Cacna1s) exon 29 in mice. These mice displayed normal overall motor performance, although grip force and voluntary running were reduced. Continued expression of the developmental CaV1.1e splice variant in adult mice caused increased calcium influx during EC coupling, altered calcium homeostasis, and spontaneous calcium sparklets in isolated muscle fibers. Contractile force was reduced and endurance enhanced. Key regulators of fiber type specification were dysregulated and the fiber type composition was shifted toward slower fibers. However, oxidative enzyme activity and mitochondrial content declined. These findings indicate that limiting calcium influx during skeletal muscle EC coupling is important for the secondary function of the calcium signal in the activity-dependent regulation of fiber type composition and to prevent muscle disease.

Original languageEnglish
Pages (from-to)1547-1559
Number of pages13
JournalDevelopment
Volume143
Issue number9
DOIs
Publication statusPublished - May 1 2016

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Skeletal Muscle
Calcium
Excitation Contraction Coupling
Muscle Contraction
Muscles
Myotonic Dystrophy
Muscle Development
Muscle Weakness
Alternative Splicing
Hand Strength
Calcium Channels
Running
Exons
Homeostasis
Enzymes

Keywords

  • Mouse
  • Muscle fiber type specification
  • Skeletal muscle excitation-contraction coupling
  • Voltage-gated calcium channel

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology

Cite this

Sultana, N., Dienes, B., Benedetti, A., Tuluc, P., Szentesi, P., Sztretye, M., ... Flucher, B. E. (2016). Restricting calcium currents is required for correct fiber type specification in skeletal muscle. Development, 143(9), 1547-1559. https://doi.org/10.1242/dev.129676

Restricting calcium currents is required for correct fiber type specification in skeletal muscle. / Sultana, Nasreen; Dienes, Beatrix; Benedetti, Ariane; Tuluc, Petronel; Szentesi, P.; Sztretye, Monika; Rainer, Johannes; Hess, Michael W.; Schwarzer, Christoph; Obermair, Gerald J.; Csernoch, L.; Flucher, Bernhard E.

In: Development, Vol. 143, No. 9, 01.05.2016, p. 1547-1559.

Research output: Contribution to journalArticle

Sultana, N, Dienes, B, Benedetti, A, Tuluc, P, Szentesi, P, Sztretye, M, Rainer, J, Hess, MW, Schwarzer, C, Obermair, GJ, Csernoch, L & Flucher, BE 2016, 'Restricting calcium currents is required for correct fiber type specification in skeletal muscle', Development, vol. 143, no. 9, pp. 1547-1559. https://doi.org/10.1242/dev.129676
Sultana, Nasreen ; Dienes, Beatrix ; Benedetti, Ariane ; Tuluc, Petronel ; Szentesi, P. ; Sztretye, Monika ; Rainer, Johannes ; Hess, Michael W. ; Schwarzer, Christoph ; Obermair, Gerald J. ; Csernoch, L. ; Flucher, Bernhard E. / Restricting calcium currents is required for correct fiber type specification in skeletal muscle. In: Development. 2016 ; Vol. 143, No. 9. pp. 1547-1559.
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