Effects of hypokalemia on the properties and expression of the (Na+,K+)-ATPase of rat skeletal muscle.
Rats maintained on a low potassium diet develop hypokalemia, which is associated with an approximately 80% decrease in the number of (Na+,K+)-ATPase molecules in skeletal muscle sarcolemma (Norgaard, A., Kjeldsen, K., and Clausen, T. (1981) Nature 293, 739-741); the skeletal muscles of the hypokalemic rats become paralyzed after exposure to insulin in low [K+] media (Otsuka, M., and Ohtsuki, I. (1970) Am. J. Physiol. 219, 1178-1182). We have been interested in the interactions between the insulin receptor and the alpha 2 isoform of the (Na+,K+)-ATPase as a mechanism for the insulin activation of (Na+,K+)-pumping and decided to use the hypokalemic rats to obtain additional information on this question. We show here that the amount of the alpha 2 isoform in the skeletal muscles of hypokalemic rats is greatly decreased as determined by immunoblotting and (Na+,K+)-ATPase activity; the effect of hypokalemia on the amount of the alpha 1 isoform is small. The mechanism of the decrease in the alpha 2 isoform is not known, but it is not due to transcriptional regulation of the alpha 2 gene because the amounts of the transcripts for this polypeptide are increased in the rats on the low potassium diet. The (Na+,K+)-pump that remains in the skeletal muscles of rats on a low potassium diet for a period of 2 weeks is still activated by insulin; under these conditions, however, insulin does not bring about a decrease in the intracellular [Na+] in contrast to the situation with normal muscle.
Hsu
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Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, Massachusetts 02138.
Guidotti
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D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D004837:Epinephrine / Q000494:pharmacology; D005786:Gene Expression Regulation; D007008:Hypokalemia / Q000201:enzymology*; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008861:Microsomes / Q000201:enzymology; D009132:Muscles / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012413:Rubidium / Q000378:metabolism; D012508:Sarcolemma / Q000201:enzymology; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*
D007328:Insulin; D010042:Ouabain; D012313:RNA; D000584:Amiloride; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D012413:Rubidium; D004837:Epinephrine