Effect of Chronic Renal Failure on NaK - ATPase al and a 2 mRNA Transcription in Rat Skeletal Muscle

Previous studies have suggested that an alteration in the expression of the NaK-ATPase of muscle may be an important determinant ofenhanced insulin sensitivity in chronic renal failure. Therefore, in the present studies we have examined the effect of uremia on the NaK-ATPase a isoforms in skeletal muscle, at the level of mRNA expression and enzymatic activity. The activity of the sodium pump, as measured ouabain-sensitive 'Rb/K uptake in soleus muscle, revealed a reduction in the activity in uremia, related to the increment in plasma creatinine values. The decrement in 86Rb uptake by the rat soleus muscle of experimental animals was associated with changes on NaK-ATPase gene product. Northern analysis of mRNA revealed isoform-specific regulation of Na,K-ATPase by uremia in skeletal muscle: a decrease of 50% in al subunit Na,K-ATPase mRNA, as compared to controls. The decrement in al mRNA correlates with the decreased activity of the Na,K-ATPase in uremia, under basal conditions and with the almost complete inhibition of the Na,K-ATPase, of uremic tissue by a concentration of 10-' M ouabain. Although the activity of the a2 isoform pump was not modified by uremia, the 3.4-kb message for this enzyme was increased 2.2-fold; this discrepancy is discussed. Altogether these findings demonstrate that the defective extrarenal potassium handling in uremia is at least dependent in the expression of a1 subunit of the Na,K-ATPase. (J. Clin. Invest. 1991. 88:2137-2141.)