title: Persistent expression of the alpha1S-dihydropyridine receptor in aged human skeletal muscle: implications for the excitation-contraction uncoupling hypothesis of sarcopenia.
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 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.
authors.affiliation: Department of Pharmacology, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Michelle
authors.initials: M
authors.lastname: Ryan
authors.forename: Gillian
authors.initials: G
authors.lastname: Butler-Browne
authors.forename: Ida
authors.initials: I
authors.lastname: Erzen
authors.forename: Vincent
authors.initials: V
authors.lastname: Mouly
authors.forename: Lars-Eric
authors.initials: LE
authors.lastname: Thornell
authors.forename: Anton
authors.initials: A
authors.lastname: Wernig
authors.forename: Kay
authors.initials: K
authors.lastname: Ohlendieck
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism; D000818:Animals; D020746:Calcium Channels, L-Type / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics
chemical_list: D020746:Calcium Channels, L-Type; D020033:Protein Isoforms; D018995:Myosin Heavy Chains