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

Abstract

Fourteen-day adrenal steroid treatment increases [(3)H]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 alpha(1)- and alpha(2)-subunits and glycoprotein beta(1)- and beta(2)-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 alpha(2) and beta(1) protein in all muscle types by 53-78% and ~50%, respectively. Dex increased alpha(1) protein only in diaphragm (65 +/- 7%). At the mRNA level in whole hindlimb muscle, Dex increased alpha(2) (6.4 +/- 0.5-fold) and beta(1) (1.54 +/- 0.15-fold) and decreased beta(2) (to 0.36 +/- 0.6 of control). In summary, alpha(2)beta(1) is the Dex-responsive pump in all skeletal muscles, and changes in alpha(2) and beta(1) mRNA levels can drive the 50% change in alpha(2)beta(1)-subunits, which can account for the reported increase in [(3)H]ouabain binding.

Contraction-induced increases in Na+-K+-ATPase mRNA levels in human skeletal muscle are not amplified by activation of additional muscle mass

“…The major endocrine regulator of Na ϩ -K ϩ -ATPase basal expression seems to be thyroid hormone (8), but cortisol and possibly growth hormone (GH) also affect Na ϩ -K ϩ -ATPase expression (8,11,12,45). Furthermore, hormonal induction of Na ϩ -K ϩ -ATPase subunit expression may be subunit specific, as evidenced by the selective upregulation of ␣ 2 and ␤ 1 mRNA and protein expression shown by analysis of ␣ 1 , ␣ 2 , ␤ 1 , and ␤ 2 expression in rat skeletal muscle after treatment with the artificial glucocorticoid dexamethasone (46). Furthermore, treatment with dexamethasone has been shown to result in a dose-dependent increase in [ 3 H]ouabain binding sites in rat skeletal muscle (10,39), confirming that changes at the mRNA level are likely to cause changes in Na ϩ -K ϩ -ATPase protein expression.…”

Severe intracellular magnesium and potassium depletion in patients after treatment with cisplatin

“…Despite a decrease in skeletal muscle K, the Na,K-ATPase concentration was normal after cisplatin treatment. This is contrary to what was expected (Dorup et al, 1988b;Clausen, 1998), and may be caused by prednisolone administered as antiemetic to cisplatin-treated patients, since it reportedly upregulates the skeletal muscle Na,K-ATPase concentration (Thompson et al, 2001). Thus, prednisolone may prevent K depletion in cisplatin treatment from reducing muscle cell K reuptake capacity further.…”

Na+, K+-ATPase content in skeletal muscle of dogs with pituitary-dependent hyperadrenocorticism

“…Plasma ACTH and cortisol concentrations were increased in dogs with PDH. Administration of exogenous glucocorticoids up to 14 days has been shown to increase the Na + , K + -ATPase content in skeletal muscle of humans and rodents [11][12][13] and it was hypothesized that the Na + , K + -ATPase content was increased in muscles of dogs with PDH. Unexpectedly, decreased Na + , K + -ATPase contents were found in skeletal muscle of dogs with PDH.…”

“…In rat muscle, the majority of Na + , K + -ATPase contains the ␣ 2 -isoform with high affinity for ouabain [8,13]. In the dog the relative Na + , K + -ATPase isozyme abundance in skeletal muscle is not known.…”

“…In the dog the relative Na + , K + -ATPase isozyme abundance in skeletal muscle is not known. Moreover, as hormones have variable influences on the individual isoforms of the Na + -, K + -pump [35], this might also contribute to the discrepancy in Na + , K + -ATPase response of rats versus dogs. In all dogs biopsies from palatine muscle contained a higher content of Na + , K + -ATPase than the medial gluteal muscle.…”