Hypokalemia decreases Na(+)-K(+)-ATPase alpha 2- but not alpha 1-isoform abundance in heart, muscle, and brain.
K+ deficiency has been linked to a loss of K+ from muscle associated with a decrease in ouabain binding and K(+)-dependent phosphatase activity. This study aimed to quantitate the Na(+)-K(+)-ATPase alpha- and beta-isoform-specific responses to hypokalemia in vivo in heart, skeletal muscle, and brain at pre- and posttranslational levels. Two-week dietary K+ restriction resulted in decreases in alpha 2-mRNA in heart and skeletal muscle to 0.60 and 0.65, and in alpha 2-protein abundance to 0.38 and 0.18 of control, respectively. The decrease in alpha 2-protein was greater than the decrease in mRNA in both tissues, suggesting translational and/or posttranslational mechanism(s) of regulation as well as pretranslational regulation in response to hypokalemia. K(+)-dependent p-nitrophenyl phosphatase (pNPPase) activity decreased in heart and skeletal muscle to 0.67 and 0.58, respectively. There were no changes in alpha 1-. or beta-mRNA or protein levels in skeletal muscle or heart. In brain, there was a similar pattern of regulation. While brain alpha 2-mRNA did not change in hypokalemia, protein levels decreased to 0.72 of control. In conclusion, hypokalemia is associated with a large decrease in expression of the alpha 2-isoform of Na(+)-K(+)-ATPase. These results support the hypothesis that in skeletal and heart muscle hypokalemia induces a decrease in Na(+)-K(+)-ATPase activity (measured as K(+)-dependent pNPPase activity) by specifically decreasing the expression of the alpha 2-isoform of Na(+)-K(+)-ATPase.(ABSTRACT TRUNCATED AT 250 WORDS)
Azuma
K K
KK
Department of Physiology and Biophysics, University of Southern California School of Medicine, Los Angeles 90033.
Hensley
C B
CB
Putnam
D S
DS
McDonough
A A
AA
D000818:Animals; D001921:Brain / Q000201:enzymology*; D007008:Hypokalemia / Q000201:enzymology*; D007527:Isoenzymes / Q000235:genetics*; D046911:Macromolecular Substances; D008297:Male; D009132:Muscles / Q000201:enzymology*; D009206:Myocardium / Q000201:enzymology*; D009928:Organ Specificity; D012333:RNA, Messenger / Q000235:genetics* / Q000302:isolation & purification; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics*
D007527:Isoenzymes; D046911:Macromolecular Substances; D012333:RNA, Messenger; D000254:Sodium-Potassium-Exchanging ATPase