Unchanged [3H]ouabain binding site content but reduced Na+-K+ pump α2-protein abundance in skeletal muscle in older adults

McKenna MJ, Perry BD, Serpiello FR, Caldow MK, Levinger P, Cameron-Smith D, Levinger I. Unchanged [H-3]ouabain binding site content but reduced Na+-K+ pump alpha(2)-protein abundance in skeletal muscle in older adults. J Appl Physiol 113: 1505-1511, 2012. First published August 30, 2012; doi:10.1152/japplphysiol.01032.2011.-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 alpha(1)-, alpha(2)-, alpha(3)-, beta(1)-, beta(2)-, and beta(3)-isoform gene expression (real-time RT-PCR), protein abundance (immunoblotting), and NKA total content ([H-3]ouabain binding sites). The Elderly had lower peak oxygen consumption (-36.7%, P = 0.000), strength (-36.3%, P = 0.001), NKA alpha(2)-(-24.4%, 11.9 +/- 4.4 vs. 9.0 +/- 2.7 arbitrary units, P = 0.049), and NKA beta(3)-protein abundance (-23.0%, P = 0.041) than Young. The beta(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 [H-3] ouabain binding site content. Thus skeletal muscle in elderly individuals was characterized by decreased NKA alpha(2)- and beta(3)-protein abundance, but unchanged alpha(1) abundance and [H-3]ouabain binding. The latter was likely caused by reduced alpha(2) abundance with aging, preventing an otherwise higher [H-3]ouabain binding that might occur with a greater membrane density in smaller muscle fibers. Further study is required to verify reduced muscle NKA alpha(2) with aging and possible contributions to impaired exercise capability and daily living activities.