Persistent expression of the α1S-dihydropyridine receptor in aged human skeletal muscle: Implications for the excitation-contraction uncoupling hypothesis of sarcopenia

  • Authors:
    • Michelle Ryan
    • Gillian Butler-Browne
    • Ida Erzen
    • Vincent Mouly
    • Lars-Eric Thornell
    • Anton Wernig
    • Kay Ohlendieck
  • View Affiliations

  • Published online on: April 1, 2003     https://doi.org/10.3892/ijmm.11.4.425
  • Pages: 425-434
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Abstract

Previous studies on aged animal muscle suggest that excitation-contraction uncoupling and fibre transitions play a central role in sarcopenia, the progressive loss and functional decline of aging skeletal muscle fibres. A drastic reduction in the voltage-sensing α1S-subunit of the transverse-tubular dihydropyridine receptor is believed to be the underlying cause for a decreased transmission of the surface depolarization signal into Ca2+-mediated muscle contraction. Extending these studies to human muscle, we asked whether potential changes in the relative expression of the voltage sensor occur in senescent human fibres. For internal standardization and as markers of potential fast-to-slow transitions, the fast isoforms of the Ca2+-binding element calsequestrin and the myosin heavy chain were employed. Besides small inter-individual variations in expression levels, the microsomal immunoblot analysis of vastus lateralis autopsy specimens from male humans aged 18 to 82 years of age showed no major changes in the relative abundance of the α1S- and α2-dihydropyridine receptor, fast calsequestrin and the slow/fast myosin heavy chains. The oligomeric status of the α1S-dihydropyridine receptor was unaltered in aged fibres. Biochemical assays revealed no significant modifications in Ca2+-ATPase activity and a reduced Ca2+-binding capacity in aged human muscle preparations. Although impairments of other Ca2+-regulatory proteins and/or disturbed protein-protein interactions might be involved in the pathophysiological changes of sarcopenia, dihydropyridine receptor and calsequestrin expression seem to be preserved during the aging process of human skeletal muscle fibres. Hence, the supposition that excitation-contraction uncoupling is responsible for sarcopenia can not be transferred from animal models to senescent human muscle without modifications.

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April 2003
Volume 11 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Ryan M, Butler-Browne G, Erzen I, Mouly V, Thornell L, Wernig A and Ohlendieck K: Persistent expression of the α1S-dihydropyridine receptor in aged human skeletal muscle: Implications for the excitation-contraction uncoupling hypothesis of sarcopenia. Int J Mol Med 11: 425-434, 2003
APA
Ryan, M., Butler-Browne, G., Erzen, I., Mouly, V., Thornell, L., Wernig, A., & Ohlendieck, K. (2003). Persistent expression of the α1S-dihydropyridine receptor in aged human skeletal muscle: Implications for the excitation-contraction uncoupling hypothesis of sarcopenia. International Journal of Molecular Medicine, 11, 425-434. https://doi.org/10.3892/ijmm.11.4.425
MLA
Ryan, M., Butler-Browne, G., Erzen, I., Mouly, V., Thornell, L., Wernig, A., Ohlendieck, K."Persistent expression of the α1S-dihydropyridine receptor in aged human skeletal muscle: Implications for the excitation-contraction uncoupling hypothesis of sarcopenia". International Journal of Molecular Medicine 11.4 (2003): 425-434.
Chicago
Ryan, M., Butler-Browne, G., Erzen, I., Mouly, V., Thornell, L., Wernig, A., Ohlendieck, K."Persistent expression of the α1S-dihydropyridine receptor in aged human skeletal muscle: Implications for the excitation-contraction uncoupling hypothesis of sarcopenia". International Journal of Molecular Medicine 11, no. 4 (2003): 425-434. https://doi.org/10.3892/ijmm.11.4.425