Linkage of aerobic glycolysis to sodium-potassium transport in rat skeletal muscle. Implications for increased muscle lactate production in sepsis.

Abstract

Although a linkage between aerobic glycolysis and sodiumpotassium transport has been demonstrated in diaphragm, vascular smooth muscle, and other cells, it is not known whether this linkage occurs in skeletal muscle generally. Metabolism of intact hind-leg muscles from young rats was studied in vitro under aerobic incubation conditions. When sodium influx into rat extensor digitorum longus (EDL) and soleus muscles was facilitated by the sodium ionophore monensin, muscle weight gain and production of lactate and alanine were markedly stimulated in a dose-dependent manner. Although lactate production rose in both muscles, it was more pronounced in EDL than in soleus. Monensininduced lactate production was inhibited by ouabain or by incubation in sodium-free medium. Preincubation in potassium-free medium followed by potassium re-addition also stimulated ouabain-inhibitable lactate release. Replacement of glucose in the incubation medium with pyruvate abolished monensin-induced lactate production but exacerbated monensin-induced weight gain. Muscles from septic or endotoxin-treated rats exhibited an increased rate of lactate production in vitro that was partially inhibited by ouabain. Increases muscle lactate production in sepsis may reflect linked increases in activity of the Na ϩ , K ϩ -ATPase, consumption of ATP and stimulation of aerobic glycolysis. ( J. Clin. Invest. 1996. 98:2388-2397.)

MCT1 and its accessory protein CD147 are differentially regulated by TSH in rat thyroid cells

“…These studies suggest that aerobic glycolysis is important for membrane enzyme and transport activities. More recent studies in rat skeletal muscle show that there is a strong link between aerobic glycolysis and Na ϩ -K ϩ -ATPase activity (15). Diverse treatments, known to raise muscle intracellular Na ϩ concentration and increase Na ϩ -K ϩ -ATPase activity, stimulated aerobic glycolysis and lactate production.…”

Sepsis Correlated with Increased Erythrocyte Na^+ Content and Na^+-K^+ Pump Activity

“…Recent findings indicate that muscles from septic rats exhibit an increased rate of lactate production that was partially inhibited by ouabain, suggesting a linking of aerobic glycolysis with increases in Na + ,K + -ATPase activity [16]. These metabolic effects may explain the correlation between Na + transport abnormalities and the severity of sepsis.…”

A New View of Carcinogenesis and an Alternative Approach to Cancer Therapy

“…Other strategies could be used to inhibit or exploit the increased glycolytic activity of cancer cells. Because an increase in the activity of the Na + /K + -ATPase pump is associated with the activation of glycolysis (116,117), the inhibition of this pump (for example, by cardiac glycosides) may result in the inhibition of glycolysis and the selective killing of cancer cells (113,118). The activation of glycolysis is known to increase the concentration of protons in the cytosol.…”