title: Unchanged [3H]ouabain binding site content but reduced Na+-K+ pump α2-protein abundance in skeletal muscle in older adults.
abstract: Aging is associated with reduced muscle mass, weakness, and increased fatigability. In skeletal muscle, the Na(+)-K(+) pump (NKA) is important in regulating Na(+)-K(+) gradients, membrane excitability, and thus contractility, but the effects of aging on muscle NKA are unclear. We investigated whether aging is linked with reduced muscle NKA by contrasting muscle NKA isoform gene expression and protein abundance, and NKA total content in 17 Elderly (66.8 ± 6.4 yr, mean ± SD) and 16 Young adults (23.9 ± 2.2 yr). Participants underwent peak oxygen consumption assessment and a vastus lateralis muscle biopsy, which was analyzed for NKA α(1)-, α(2)-, α(3)-, β(1)-, β(2)-, and β(3)-isoform gene expression (real-time RT-PCR), protein abundance (immunoblotting), and NKA total content ([(3)H]ouabain binding sites). The Elderly had lower peak oxygen consumption (-36.7%, P = 0.000), strength (-36.3%, P = 0.001), NKA α(2)- (-24.4%, 11.9 ± 4.4 vs. 9.0 ± 2.7 arbitrary units, P = 0.049), and NKA β(3)-protein abundance (-23.0%, P = 0.041) than Young. The β(3)-mRNA was higher in Elderly compared with Young (P = 0.011). No differences were observed between groups for other NKA isoform mRNA or protein abundance, or for [(3)H]ouabain binding site content. Thus skeletal muscle in elderly individuals was characterized by decreased NKA α(2)- and β(3)-protein abundance, but unchanged α(1) abundance and [(3)H]ouabain binding. The latter was likely caused by reduced α(2) abundance with aging, preventing an otherwise higher [(3)H]ouabain binding that might occur with a greater membrane density in smaller muscle fibers. Further study is required to verify reduced muscle NKA α(2) with aging and possible contributions to impaired exercise capability and daily living activities.
authors.affiliation: Institute of Sport, Exercise and Active Living, Muscle, Ions and Exercise Group, Victoria University, Melbourne, VIC 8001, Australia. michael.mckenna@vu.edu.au
authors.forename: Michael J
authors.initials: MJ
authors.lastname: McKenna
authors.forename: Ben D
authors.initials: BD
authors.lastname: Perry
authors.forename: Fabio R
authors.initials: FR
authors.lastname: Serpiello
authors.forename: Marissa K
authors.initials: MK
authors.lastname: Caldow
authors.forename: Pazit
authors.initials: P
authors.lastname: Levinger
authors.forename: David
authors.initials: D
authors.lastname: Cameron-Smith
authors.forename: Itamar
authors.initials: I
authors.lastname: Levinger
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging / Q000378:metabolism*; D001665:Binding Sites; D001706:Biopsy; D015153:Blotting, Western; D027682:Cation Transport Proteins / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D015536:Down-Regulation; D005080:Exercise Test; D005260:Female; D006801:Humans; D007537:Isometric Contraction; D008297:Male; D008875:Middle Aged; D053580:Muscle Strength; D010042:Ouabain / Q000378:metabolism*; D010101:Oxygen Consumption; D052097:Quadriceps Muscle / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*; D014316:Tritium; D055815:Young Adult
chemical_list: C488756:ATP1A3 protein, human; C503551:ATP1B1 protein, human; C504190:ATP1B2 protein, human; C519304:ATP1B3 protein, human; D027682:Cation Transport Proteins; D015816:Cell Adhesion Molecules, Neuronal; D012333:RNA, Messenger; D014316:Tritium; D010042:Ouabain; C499076:ATP1A1 protein, human; C498531:ATP1A2 protein, human; D000251:Adenosine Triphosphatases; D000254:Sodium-Potassium-Exchanging ATPase