Temporal responses of oxidative vs. glycolytic skeletal muscles to K⁺ deprivation: Na⁺ pumps and cell cations

Abstract

When K+ output exceeds input, skeletal muscle releases intracellular fluid K+ to buffer the fall in extracellular fluid (ECF) K+. To investigate the mechanisms and muscle specificity of the K+ shift, rats were fed K+-deficient chow for 2–10 days, and two muscles at phenotypic extremes were studied: slow-twitch oxidative soleus and fast-twitch glycolytic white gastrocnemius (WG). After 2 days of low-K+ chow, plasma K+ concentration ([K+]) fell from 4.6 to 3.7 mM, and Na+-K+-ATPase α2 (not α1) protein levels in both muscles, measured by immunoblotting, decreased 36%. Cell [K+] decreased from 116 to 106 mM in soleus and insignificantly in WG, indicating that α2 can decrease before cell [K+]. After 5 days, there were further decreases in α2 (70%) and β2 (22%) in WG, not in soleus, whereas cell [K+] decreased and cell [Na+] increased by 10 mM in both muscles. By 10 days, plasma [K+] fell to 2.9 mM, with further decreases in WG α2 (94%) and β2 (70%); cell [K+] fell 19 mM in soleus and 24 mM in WG compared with the control, and cell [Na+] increased 9 mM in soleus and 15 mM in WG; total homogenate Na+-K+-ATPase activity decreased 19% in WG and insignificantly in soleus. Levels of α2, β1, and β2 mRNA were unchanged over 10 days. The ratios of α2 to α1 protein levels in both control muscles were found to be nearly 1 by using the relative changes in α-isoforms vs. β1- (soleus) or β2-isoforms (WG). We conclude that the patterns of regulation of Na+ pump isoforms in oxidative and glycolytic muscles during K+ deprivation mediated by posttranscriptional regulation of α2β1 and α2β2 are distinct and that decreases in α2-isoform pools can occur early enough in both muscles to account for the shift of K+ to the ECF.

Altered expression and insulin-induced trafficking of Na+-K+-ATPase in rat skeletal muscle: effects of high-fat diet and exercise

“…Previous reports indicate that K ϩ depletion is associated with reduced Na ϩ -K ϩ -ATPase ␣ 2 -subunit expression in skeletal muscle (51), furthermore that high-fat feeding is sometimes associated with decreased K ϩ intake due to a low K ϩ content in some commercial high-fat diets (10), leading to decreased insulin-stimulated K ϩ flux into skeletal muscle. Therefore, there is the possibility that some of the changes in Na the chow diet used in the current study had similar K ϩ content.…”

“…Apart from classical regulation by steroid and thyroid hormones (38), the molecular regulation of genes encoding Na ϩ -K ϩ -ATPase subunits under physiological conditions where Na ϩ -K ϩ -ATPase expression is altered, such as hypokalemia (50,51), diabetes (15,44), or exercise training (11,30,44), is largely unknown. The Na ϩ -K ϩ -ATPase ␣ 2 -subunit gene promoter contains consensus sequences for several transcription factors, including AP-1, AP-2, NF-1, and Sp-1 (45).…”

“…Multiple isoforms of ␣-and ␤-subunits are expressed by and each is encoded by a different gene (34). Adult skeletal muscle expresses two ␣-subunits (␣ 1 and ␣ 2 ) and two ␤-subunits (␤ 1 and ␤ 2 ), and the relative abundance of each isoform and Na ϩ -K ϩ -ATPase activity is regulated in a fiber type-specific manner (26,48,50,51). Following insulin exposure or contraction, Na ϩ -K ϩ -ATPase unit abundance in the plasmalemma and T-tubules of skeletal muscle is increased (4).…”

“…Furthermore, in type 2 diabetic patients, Na ϩ -K ϩ -ATPase expression in skeletal muscle (15) and erythrocytes (36) is decreased, and restored by insulin treatment (44). Na ϩ -K ϩ -ATPase protein expression is differently regulated by exercise training, starvation, hypokalemia and type 1 and type 2 diabetes mellitus (15,44,50,51). Physical activity and exercise training reduces the risk of developing type 2 diabetes and obesity (52,60), in part by increased skeletal muscle protein expression of key genes important for glucose uptake and utilization (9,43).…”

Na+-K+-ATPase properties in rat heart and skeletal muscle 3 mo after coronary artery ligation

“…The heart mainly consists of the ␣ 1 ␤ 1 -and ␣ 3 ␤ 1 -subunit combinations (36). The ␤ 3 -isoform was not probed for at the time of this study because previous investigators have concluded that little of this isoform exists in the skeletal muscles of adult rats (1,53). However, recent studies have reported the presence of ␤ 3 in a variety of muscles (22,39).…”