Tissue-specific modulation of Na, K-ATPase α-subunit gene expression in uremic rats

Tissue-specific modulation of Na, K-ATPase α-subunit gene expression in uremic rats. Chronic renal failure in the rat is associated with an impaired extrarenal potassium handling, whereas a renal adaptive mechanism of the remaining nephrons has been described. To understand the molecular basis of potassium homeostasis during renal failure we investigated the in vitro pump activity and the catalytic mRNA transcription in three different tissues: skeletal muscle, isolated adipocytes and kidney. The activity of the sodium pump, as measured by ouabain-sensitive 86 Rb/K uptake in isolated adipocytes and skeletal muscle fibers, revealed a significant reduction of the pump activity in uremic rats. The reduction of the Na, K-ATPase activity in adipose tissue was associated with a similar decrement of both catalytic subunits (α1 and α2), whereas in the skeletal muscle tissue was only related to a decrease in the activity of the α1 isoform. The expression of rat Na, K-ATPase catalytic isoforms mRNAs in kidney, muscle and adipose tissue from control and chronic renal failure rats was investigated at the molecular level with cDNA probes specific for the catalytic isoforms (α1 and α2). Northern blot analysis revealed that the respective catalytic mRNAs of uremic rats are regulated in a tissue-specific manner that are in agreement with the sodium-potassium pump activity. Muscle and adipose tissue showed a decrement in the levels of expression for the α1 isoform mRNA. In contrast to these tissues, an increment in α1 mRNA expression was observed in the kidney of rats with chronic renal failure. The α2 mRNA was expressed primarily in muscle and adipose tissue, but only in this last tissue was a decrement in the expression observed. Then, each tissue examined exhibits a distinct pattern of expression for the Na, K-ATPase catalytic α isoforms during chronic renal failure.