Vastus lateralis Na(+)-K(+)-ATPase activity, protein, and isoform distribution in chronic obstructive pulmonary...

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 alpha (alpha1, alpha2, alpha3) and beta (beta1, beta2, beta3) 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 x mg protein(-1) h(-1)). No differences between groups were observed for pump concentration (259 +/- 15 vs. 243 +/- 17 pmol x g wet weight). For the isoforms, alpha1 was decreased by 28% (P < 0.05), and alpha2 was increased by 12% (P < 0.05) in COPD compared with CON. No differences between groups were observed for alpha3 or for the beta 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 (alpha1, alpha2), 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.