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

Abstract

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 (B_max) 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 (α and β) expression. In the present study, we tested the hypothesis that reductions in B_maxwould coincide with alterations in the α- and β-subunit expression of the sarcolemmal Na⁺-K⁺-ATPase of rats with CHF. Moreover, we tested the hypothesis that exercise training would increase B_maxalong with producing significant changes in α- and β-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 (V˙o_2 max) and endurance capacity (run time to fatigue) were reduced in MI rats compared with sham. B_maxin the soleus and plantaris muscles and the expression of the α₂-isoform of the Na⁺-K⁺-ATPase in the red portion of the gastrocnemius (gastrocnemius_red) muscle were reduced in MI rats. After ET, V˙o_2 maxand run time to fatigue were increased in the MI-T group of rats. This coincided with increases in soleus and plantaris B_maxand the expression of the α₂-isoform in the gastrocnemius_redmuscle. In addition, the expression of the β₂-isoform of the gastrocnemius_redmuscle 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 B_maxand isoform expression, can be partially reversed by ET.