Vastus lateralis NA+‐K+‐ATpase activity,protein, and isoform distribution in chronic obstructive pulmonary disease |
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Authors: | Henry James Green PhD Margaret Elizabeth Burnett MSc Christine Linda D'Arsigny MD Katherine Alexandra Webb BSc Ian McBride BSc Jing Ouyang MD Dennis Einan O'Donnell MD |
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Institution: | 1. Department of Kinesiology, University of Waterloo, Waterloo, Ontario N2L3G1, Canada;2. Division of Respiratory and Critical Care Medicine, Department of Medicine, Queen's University, Kingston, Ontario, Canada |
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Abstract: | In this study we investigate the hypothesis that protein abundance, isoform distribution, and maximal catalytic activity of sodium–potassium–adenosine triphosphatase (Na+‐K+‐ATPase) would be altered in muscle of patients with moderate to severe chronic obstructive pulmonary disease (COPD). Tissue samples were obtained from the vastus lateralis of 10 patients with COPD (mean ± SE: age = 67 ± 2.9 years; FEV1 = 39 ± 5.5%) and 10 healthy, matched controls (CON: age = 68 ± 2 years; FEV1 = 114 ± 4.2%). The samples were assessed for maximal catalytic activity (Vmax) of the enzyme using the K+‐stimulated 3‐O‐methylfluorescein‐phosphatase (3‐O‐MFPase) assay, enzyme abundance using the 3H]‐ouabain assay, and isoform content of both α (α1, α2, α3) and β (β1, β2, β3) using Western blot techniques. A 19.4% lower (P < 0.05) Vmax was observed in COPD compared with CON (90.7 ± 6.7 vs. 73.1 ± 4.7 nmol · mg protein?1 h?1). No differences between groups were observed for pump concentration (259 ± 15 vs. 243 ± 17 pmol · g wet weight). For the isoforms, α1 was decreased by 28% (P < 0.05), and α2 was increased by 12% (P < 0.05) in COPD compared with CON. No differences between groups were observed for α3 or for the β isoforms. We conclude that moderate COPD compromises Vmax, which occurs in the absence of changes in pump abundance. The reduction in Vmax could be due to a shift in isoform expression (α1, α2), alterations in intrinsic regulation, or to structural changes in the enzyme. The changes observed in the catalytic activity of the pump could have major effects on membrane excitability and fatigability, which are typically compromised in COPD. Muscle Nerve, 2009 |
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Keywords: | cation transport Na+‐K+‐ATPase properties obstructive lung disease quadriceps isoforms excitation |
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