Glucocorticoids increase sodium pump α2- and β1-subunit abundance and mRNA in rat skeletal muscle

Abstract

Fourteen-day adrenal steroid treatment increases [3H]ouabain binding sites 22–48% in muscle biopsies from patients treated with adrenal steroids for chronic obstructive lung disease and in rats treated with dexamethasone (Dex). Ouabain binding measures plasma membrane sodium pumps (Na+-K+-ATPase) with isoform-dependent affinity. In this study we have established the specific pattern of Dex regulation of sodium pump isoform protein and mRNA levels in muscle. Rats were infused with Dex (0.1 mg/kg per day) or vehicle for 14 days. Abundance of sodium pump catalytic α1- and α2-subunits and glycoprotein β1- and β2-subunits was determined by immunoblot in soleus, extensor digitorum longus, whole gastrocnemius, and diaphragm and was normalized to the mean vehicle control value. Dex increased α2 and β1 protein in all muscle types by 53–78% and ∼50%, respectively. Dex increased α1protein only in diaphragm (65 ± 7%). At the mRNA level in whole hindlimb muscle, Dex increased α2 (6.4 ± 0.5-fold) and β1 (1.54 ± 0.15-fold) and decreased β2 (to 0.36 ± 0.6 of control). In summary, α2β1 is the Dex-responsive pump in all skeletal muscles, and changes in α2 and β1mRNA levels can drive the 50% change in α2β1-subunits, which can account for the reported increase in [3H]ouabain binding.