TISSUE-SPECIFIC MODULATION OF NA, K-ATPASE ALPHA-SUBUNIT GENE-EXPRESSION IN UREMIC RATS

Chronic renal failure in the rat is associated with an impaired extrar enal potassium handling, whereas a renal adaptive mechanism of the rem aining nephrons has been described. To understand the molecular basis of potassium homeostasis during renal failure we investigated the in v itro pump activity and the catalytic mRNA transcription in three diffe rent tissues: skeletal muscle, isolated adipocytes and kidney. The act ivity of the sodium pump, as measured by ouabain-sensitive Rb-86/K upt ake in isolated adipocytes and skeletal muscle fibers, revealed a sign ificant reduction of the pump activity in uremic rats. The reduction o f the Na, K-ATPase activity in adipose tissue was associated with a si milar decrement of both catalytic subunits (alpha 1 and alpha 2), wher eas in the skeletal muscle tissue was only related to a decrease in th e activity of the alpha 1 isoform. The expression of rat Na, K-ATPase catalytic isoforms mRNAs in kidney, muscle and adipose tissue from con trol and chronic renal failure rats was investigated at the molecular level, with cDNA probes specific for the catalytic isoforms (alpha 1 a nd alpha 2). Northern blot analysis revealed that the respective catal ytic mRNAs of uremic rats are regulated in a tissue-specific manner th at are in agreement with the sodium-potassium pump activity. Muscle an d adipose tissue showed a decrement in the levels of expression for th e alpha 1 isoform mRNA. In contrast to these tissues, an increment in alpha 1 mRNA expression was observed in the kidney of rats with chroni c renal failure. The alpha 2 mRNA was expressed primarily in muscle an d adipose tissue, but only in this last tissue was a decrement in the expression observed. Then, each tissue examined exhibits a distinct pa ttern of expression for the Na, K-ATPase catalytic alpha isoforms duri ng chronic renal failure.