Change search
ReferencesLink to record
Permanent link

Direct link
Persistent expression of the alpha(1S)-dihydropyridine receptor in aged human skeletal muscle: Implications for the excitation-contraction uncoupling hypothesis of sarcopenia
Show others and affiliations
2003 (English)In: International Journal of Molecular Medicine, ISSN 1107-3756, E-ISSN 1791-244X, Vol. 11, no 4, 425-434 p.Article in journal (Refereed) Published
Abstract [en]

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 alpha1S-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 alpha1S- and alpha2-dihydropyridine receptor, fast calsequestrin and the slow/fast myosin heavy chains. The oligomeric status of the alpha1S-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.

Place, publisher, year, edition, pages
2003. Vol. 11, no 4, 425-434 p.
Keyword [en]
aging muscle, calsequestrin, dihydropyridine receptor, excitation-contraction coupling, excitation-contraction uncoupling, sarcopenia
National Category
Basic Medicine
URN: urn:nbn:se:umu:diva-82684ISI: 000181565400003PubMedID: 12632093OAI: diva2:662162
Available from: 2013-11-06 Created: 2013-11-06 Last updated: 2014-04-16Bibliographically approved

Open Access in DiVA

No full text


Search in DiVA

By author/editor
Thornell, Lars-Eric
By organisation
In the same journal
International Journal of Molecular Medicine
Basic Medicine

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 34 hits
ReferencesLink to record
Permanent link

Direct link