Skeletal muscle Na,K-ATPase alpha and beta subunit protein levels respond to hypokalemic challenge with isoform and muscle type specificity.
During potassium deprivation, skeletal muscle loses K+ to buffer the fall in extracellular K+. Decreased active K+ uptake via the sodium pump, Na,K-ATPase, contributes to the adjustment. Skeletal muscle expresses alpha1, alpha2, beta1, and beta2 isoforms of the Na, K-ATPase alphabeta heterodimer. This study was directed at testing the hypothesis that K+ loss from muscle during K+ deprivation is a function of decreased expression of specific isoforms expressed in a muscle type-specific pattern. Isoform abundance was measured in soleus, red and white gastrocnemius, extensor digitorum longus, and diaphragm by immunoblot. alpha2 expression was uniform across control muscles, whereas alpha1 and beta1 were twice as high in oxidative (soleus and diaphragm) as in fast glycolytic (white gastrocnemius) muscles, and beta2 expression was reciprocal: highest in white gastrocnemius and barely detectable in soleus and diaphragm. Following 10 days of potassium deprivation plasma K+ fell from 4.0 to 2.3 mM, and there were distinct responses in glycolytic versus oxidative muscles. In glycolytic white gastrocnemius alpha2 and beta2 fell 94 and 70%, respectively; in mixed red gastrocnemius and extensor digitorum longus both fell 60%, and beta1 fell 25%. In oxidative soleus and diaphragm alpha2 fell 55 and 30%, respectively, with only minor changes in beta1. Although decreases in alpha2 and beta2 expression are much greater in glycolytic than oxidative muscles during K+ deprivation, both types of muscle lose tissue K+ to the same extent, a 20% decrease, suggesting that multiple mechanisms are in place to regulate the release of skeletal muscle cell K+.
Thompson
C B
CB
Department of Physiology and Biophysics, University of Southern California School of Medicine, Los Angeles, California 90033, USA.
McDonough
A A
AA
D000818:Animals; D007008:Hypokalemia / Q000201:enzymology*; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology*; D011233:Precipitin Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D007527:Isoenzymes; D000254:Sodium-Potassium-Exchanging ATPase