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J Appl Physiol 94: 2225-2236, 2003. First published January 31, 2003; doi:10.1152/japplphysiol.00279.2002
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Vol. 94, Issue 6, 2225-2236, June 2003

Training-induced changes in skeletal muscle Na+-K+ pump number and isoform expression in rats with chronic heart failure

Bryan Helwig1, Katherine M. Schreurs1, Joslyn Hansen2, K. Sue Hageman1, Michael G. Zbreski2, Richard M. McAllister1,2, Kathy E. Mitchell1,2,*, and Timothy I. Musch1,2,*

Departments of 1 Anatomy and Physiology and 2 Kinesiology, Kansas State University, Manhattan, Kansas 66506-5802

The mechanisms responsible for the decrements in exercise performance in chronic heart failure (CHF) remain poorly understood, but it has been suggested that sarcolemmal alterations could contribute to the early onset of muscular fatigue. Previously, our laboratory demonstrated that the maximal number of ouabain binding sites (Bmax) is reduced in the skeletal muscle of rats with CHF (Musch TI, Wolfram S, Hageman KS, and Pickar JG. J Appl Physiol 92: 2326-2334, 2002). These reductions may coincide with changes in the Na+-K+-ATPase isoform (alpha  and beta ) expression. In the present study, we tested the hypothesis that reductions in Bmax would coincide with alterations in the alpha - and beta -subunit expression of the sarcolemmal Na+-K+-ATPase of rats with CHF. Moreover, we tested the hypothesis that exercise training would increase Bmax along with producing significant changes in alpha - and beta -subunit expression. Rats underwent a sham operation (sham; n = 10) or a surgically induced myocardial infarction followed by random assignment to either a control (MI; n = 16) or exercise training group (MI-T; n = 16). The MI-T rats performed exercise training (ET) for 6-8 wk. Hemodynamic indexes demonstrated that MI and MI-T rats suffered from severe left ventricular dysfunction and congestive CHF. Maximal oxygen uptake (VO2 max) and endurance capacity (run time to fatigue) were reduced in MI rats compared with sham. Bmax in the soleus and plantaris muscles and the expression of the alpha 2-isoform of the Na+-K+-ATPase in the red portion of the gastrocnemius (gastrocnemiusred) muscle were reduced in MI rats. After ET, VO2 max and run time to fatigue were increased in the MI-T group of rats. This coincided with increases in soleus and plantaris Bmax and the expression of the alpha 2-isoform in the gastrocnemiusred muscle. In addition, the expression of the beta 2-isoform of the gastrocnemiusred muscle was increased in the MI-T rats compared with their sedentary counterparts. This study demonstrates that CHF-induced alterations in skeletal muscle Na+-K+-ATPase, including Bmax and isoform expression, can be partially reversed by ET.

ouabain; exercise; performance; oxygen uptake; congestive heart failure

* The laboratories of K. E. Mitchell and T. I. Musch contributed equally to experiments found in the present investigaton.




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