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. 1996 Nov 15;98(10):2388–2397. doi: 10.1172/JCI119052

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

J H James 1, C H Fang 1, S J Schrantz 1, P O Hasselgren 1, R J Paul 1, J E Fischer 1
PMCID: PMC507691  PMID: 8941658

Abstract

Although a linkage between aerobic glycolysis and sodium-potassium 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. Monensin-induced 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+, K+-ATPase, consumption of ATP and stimulation of aerobic glycolysis.

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Selected References

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  1. Angerås U., Hall-Angerås M., Wagner K. R., James H., Hasselgren P. O., Fischer J. E. Tissue metabolite levels in different types of skeletal muscle during sepsis. Metabolism. 1991 Nov;40(11):1147–1151. doi: 10.1016/0026-0495(91)90208-e. [DOI] [PubMed] [Google Scholar]
  2. Bihler I., Sawh P. C., Charles P. Stimulation of glucose transport in skeletal muscle by the sodium ionophore monensin. Biochim Biophys Acta. 1985 Nov 21;821(1):30–36. doi: 10.1016/0005-2736(85)90149-x. [DOI] [PubMed] [Google Scholar]
  3. Borst C., Hempelmann R., Herzig S., Mohr K. Modulation of ouabain binding in beating ventricular myocardium from guinea-pigs: effects of lidocaine and monensin. Pharmacol Toxicol. 1991 Apr;68(4):243–248. doi: 10.1111/j.1600-0773.1991.tb01232.x. [DOI] [PubMed] [Google Scholar]
  4. Campbell J. D., Paul R. J. The nature of fuel provision for the Na+,K(+)-ATPase in porcine vascular smooth muscle. J Physiol. 1992 Feb;447:67–82. doi: 10.1113/jphysiol.1992.sp018991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chiao J. J., Jones W. G., 2nd, Shires G. T., 3rd, Barber A. E., Shires G. T. Effect of sepsis on intracellular sodium activity, sodium concentration, and water content in thermal injured rat. Circ Shock. 1992 Sep;38(1):42–49. [PubMed] [Google Scholar]
  6. Clausen T., Flatman J. A. The effect of catecholamines on Na-K transport and membrane potential in rat soleus muscle. J Physiol. 1977 Sep;270(2):383–414. doi: 10.1113/jphysiol.1977.sp011958. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Clausen T. The relationship between the transport of glucose and cations across cell membranes in isolated tissues. I. Stimulation of glycogen deposition and inhibition of lactic acid production in diaphragm, induced by ouabain. Biochim Biophys Acta. 1965 Sep 27;109(1):164–171. doi: 10.1016/0926-6585(65)90100-7. [DOI] [PubMed] [Google Scholar]
  8. Clausen T. The relationship between the transport of glucose and cations across cell membranes in isolated tissues. II. Effects of K+-free medium, ouabain and insulin upon the fate of glucose in rat diaphragm. Biochim Biophys Acta. 1966 Jul 13;120(3):361–368. doi: 10.1016/0926-6585(66)90303-7. [DOI] [PubMed] [Google Scholar]
  9. Erecińska M., Dagani F., Nelson D., Deas J., Silver I. A. Relations between intracellular ions and energy metabolism: a study with monensin in synaptosomes, neurons, and C6 glioma cells. J Neurosci. 1991 Aug;11(8):2410–2421. doi: 10.1523/JNEUROSCI.11-08-02410.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Everts M. E., Clausen T. Activation of the Na-K pump by intracellular Na in rat slow- and fast-twitch muscle. Acta Physiol Scand. 1992 Aug;145(4):353–362. doi: 10.1111/j.1748-1716.1992.tb09375.x. [DOI] [PubMed] [Google Scholar]
  11. Fagan J. M., Tischler M. E. Effects of oxygen deprivation on incubated rat soleus muscle. Life Sci. 1989;44(10):677–681. doi: 10.1016/0024-3205(89)90473-6. [DOI] [PubMed] [Google Scholar]
  12. Gibson W. H., Cook J. J., Gatipon G., Moses M. E. Effect of endotoxin shock on skeletal muscle cell membrane potential. Surgery. 1977 May;81(5):571–577. [PubMed] [Google Scholar]
  13. Gore D. C., Jahoor F., Hibbert J. M., DeMaria E. J. Lactic acidosis during sepsis is related to increased pyruvate production, not deficits in tissue oxygen availability. Ann Surg. 1996 Jul;224(1):97–102. doi: 10.1097/00000658-199607000-00015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Graser T. A., Godel H. G., Albers S., Földi P., Fürst P. An ultra rapid and sensitive high-performance liquid chromatographic method for determination of tissue and plasma free amino acids. Anal Biochem. 1985 Nov 15;151(1):142–152. doi: 10.1016/0003-2697(85)90064-8. [DOI] [PubMed] [Google Scholar]
  15. Hannon R. J., Boston V. E. Fluid and ion redistribution in skeletal muscle in an animal sepsis model. J Pediatr Surg. 1990 Jun;25(6):599–603. doi: 10.1016/0022-3468(90)90342-7. [DOI] [PubMed] [Google Scholar]
  16. Hotchkiss R. S., Karl I. E. Reevaluation of the role of cellular hypoxia and bioenergetic failure in sepsis. JAMA. 1992 Mar 18;267(11):1503–1510. [PubMed] [Google Scholar]
  17. Hotchkiss R. S., Rust R. S., Dence C. S., Wasserman T. H., Song S. K., Hwang D. R., Karl I. E., Welch M. J. Evaluation of the role of cellular hypoxia in sepsis by the hypoxic marker [18F]fluoromisonidazole. Am J Physiol. 1991 Oct;261(4 Pt 2):R965–R972. doi: 10.1152/ajpregu.1991.261.4.R965. [DOI] [PubMed] [Google Scholar]
  18. Hotchkiss R. S., Song S. K., Neil J. J., Chen R. D., Manchester J. K., Karl I. E., Lowry O. H., Ackerman J. J. Sepsis does not impair tricarboxylic acid cycle in the heart. Am J Physiol. 1991 Jan;260(1 Pt 1):C50–C57. doi: 10.1152/ajpcell.1991.260.1.C50. [DOI] [PubMed] [Google Scholar]
  19. Hoya A., Venosa R. A. Ionic movements mediated by monensin in frog skeletal muscle. Biochim Biophys Acta. 1992 Feb 17;1104(1):123–131. doi: 10.1016/0005-2736(92)90140-h. [DOI] [PubMed] [Google Scholar]
  20. Illner H. P., Shires G. T. Membrane defect and energy status of rabbit skeletal muscle cells in sepsis and septic shock. Arch Surg. 1981 Oct;116(10):1302–1305. doi: 10.1001/archsurg.1981.01380220048008. [DOI] [PubMed] [Google Scholar]
  21. Jacobs D. O., Kobayashi T., Imagire J., Grant C., Kesselly B., Wilmore D. W. Sepsis alters skeletal muscle energetics and membrane function. Surgery. 1991 Aug;110(2):318–326. [PubMed] [Google Scholar]
  22. Jacobs D. O., Maris J., Fried R., Settle R. G., Rolandelli R. R., Koruda M. J., Chance B., Rombeau J. L. In vivo phosphorus 31 magnetic resonance spectroscopy of rat hind limb skeletal muscle during sepsis. Arch Surg. 1988 Nov;123(11):1425–1428. doi: 10.1001/archsurg.1988.01400350139022. [DOI] [PubMed] [Google Scholar]
  23. James J. H., Hasselgren P. O., King J. K., James L. E., Fischer J. E. Intracellular glutamine concentration does not decrease in all muscles during sepsis. J Surg Res. 1993 Jun;54(6):558–564. doi: 10.1006/jsre.1993.1085. [DOI] [PubMed] [Google Scholar]
  24. Jennische E., Enger E., Medegård A., Appelgren L., Haljamäe H. Correlation between tissue pH, cellular transmembrane potentials, and cellular energy metabolism during shock and during ischemia. Circ Shock. 1978;5(3):251–260. [PubMed] [Google Scholar]
  25. Kagan B. L., Baldwin R. L., Munoz D., Wisnieski B. J. Formation of ion-permeable channels by tumor necrosis factor-alpha. Science. 1992 Mar 13;255(5050):1427–1430. doi: 10.1126/science.1371890. [DOI] [PubMed] [Google Scholar]
  26. Karlstad M. D., Sayeed M. M. Effect of endotoxic shock on basal and insulin-mediated Na+/K(+)-pump activity in rat soleus muscle. Circ Shock. 1992 Dec;38(4):222–227. [PubMed] [Google Scholar]
  27. Kennedy R. H., Seifen E., Kafiluddi R. Can maximum ouabain-sensitive 86Rb+ uptake rate be obtained by increasing Na+ influx? Eur J Pharmacol. 1986 Sep 23;129(1-2):77–85. doi: 10.1016/0014-2999(86)90338-9. [DOI] [PubMed] [Google Scholar]
  28. Lee P. L., Slocum R. H. A high-resolution method for amino acid analysis of physiological fluids containing mixed disulfides. Clin Chem. 1988 Apr;34(4):719–723. [PubMed] [Google Scholar]
  29. Liaw K. Y., Askanazi J., Michelson C. B., Kantrowitz L. R., Fürst P., Kinney J. M. Effect of injury and sepsis on high-energy phosphates in muscle and red cells. J Trauma. 1980 Sep;20(9):755–759. doi: 10.1097/00005373-198009000-00008. [DOI] [PubMed] [Google Scholar]
  30. Lipton P., Robacker K. Glycolysis and brain function: [K+]o stimulation of protein synthesis and K+ uptake require glycolysis. Fed Proc. 1983 Sep;42(12):2875–2880. [PubMed] [Google Scholar]
  31. Lynch R. M., Balaban R. S. Coupling of aerobic glycolysis and Na+-K+-ATPase in renal cell line MDCK. Am J Physiol. 1987 Aug;253(2 Pt 1):C269–C276. doi: 10.1152/ajpcell.1987.253.2.C269. [DOI] [PubMed] [Google Scholar]
  32. Lynch R. M., Balaban R. S. Energy metabolism of renal cell lines, A6 and MDCK: regulation by Na-K-ATPase. Am J Physiol. 1987 Feb;252(2 Pt 1):C225–C231. doi: 10.1152/ajpcell.1987.252.2.C225. [DOI] [PubMed] [Google Scholar]
  33. Lynch R. M., Paul R. J. Compartmentation of glycolytic and glycogenolytic metabolism in vascular smooth muscle. Science. 1983 Dec 23;222(4630):1344–1346. doi: 10.1126/science.6658455. [DOI] [PubMed] [Google Scholar]
  34. Lynch R. M., Paul R. J. Glucose uptake in porcine carotid artery: relation to alterations in active Na+-K+ transport. Am J Physiol. 1984 Nov;247(5 Pt 1):C433–C440. doi: 10.1152/ajpcell.1984.247.5.C433. [DOI] [PubMed] [Google Scholar]
  35. Maltin C. A., Delday M. I., Baillie A. G., Grubb D. A., Garlick P. J. Fiber-type composition of nine rat muscles. I. Changes during the first year of life. Am J Physiol. 1989 Dec;257(6 Pt 1):E823–E827. doi: 10.1152/ajpendo.1989.257.6.E823. [DOI] [PubMed] [Google Scholar]
  36. Mizobata Y., Prechek D., Rounds J. D., Robinson V., Wilmore D. W., Jacobs D. O. The duration of infection modifies mitochondrial oxidative capacity in rat skeletal muscle. J Surg Res. 1995 Jul;59(1):165–173. doi: 10.1006/jsre.1995.1149. [DOI] [PubMed] [Google Scholar]
  37. Mizock B. A., Falk J. L. Lactic acidosis in critical illness. Crit Care Med. 1992 Jan;20(1):80–93. doi: 10.1097/00003246-199201000-00020. [DOI] [PubMed] [Google Scholar]
  38. Nagesetty R., Paul R. J. Effects of pHi on isometric force and [Ca2+]i in porcine coronary artery smooth muscle. Circ Res. 1994 Dec;75(6):990–998. doi: 10.1161/01.res.75.6.990. [DOI] [PubMed] [Google Scholar]
  39. Parker J. C., Hoffman J. F. The role of membrane phosphoglycerate kinase in the control of glycolytic rate by active cation transport in human red blood cells. J Gen Physiol. 1967 Mar;50(4):893–916. doi: 10.1085/jgp.50.4.893. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Parrillo J. E., Parker M. M., Natanson C., Suffredini A. F., Danner R. L., Cunnion R. E., Ognibene F. P. Septic shock in humans. Advances in the understanding of pathogenesis, cardiovascular dysfunction, and therapy. Ann Intern Med. 1990 Aug 1;113(3):227–242. doi: 10.7326/0003-4819-113-3-227. [DOI] [PubMed] [Google Scholar]
  41. Paul R. J., Bauer M., Pease W. Vascular smooth muscle: aerobic glycolysis linked to sodium and potassium transport processes. Science. 1979 Dec 21;206(4425):1414–1416. doi: 10.1126/science.505014. [DOI] [PubMed] [Google Scholar]
  42. Paul R. J. Functional compartmentalization of oxidative and glycolytic metabolism in vascular smooth muscle. Am J Physiol. 1983 May;244(5):C399–C409. doi: 10.1152/ajpcell.1983.244.5.C399. [DOI] [PubMed] [Google Scholar]
  43. Paul R. J., Hardin C. D., Raeymaekers L., Wuytack F., Casteels R. Preferential support of Ca2+ uptake in smooth muscle plasma membrane vesicles by an endogenous glycolytic cascade. FASEB J. 1989 Sep;3(11):2298–2301. doi: 10.1096/fasebj.3.11.2528493. [DOI] [PubMed] [Google Scholar]
  44. Peitzman A. B., Corbett W. A., Shires G. T., 3rd, Illner H., Shires G. T., Inamdar R. Cellular function in liver and muscle during hemorrhagic shock in primates. Surg Gynecol Obstet. 1985 Nov;161(5):419–424. [PubMed] [Google Scholar]
  45. Pellerin L., Magistretti P. J. Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10625–10629. doi: 10.1073/pnas.91.22.10625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Shiono S., Fantini G. A., Roberts J. P., Chiao J., Shires G. T. Assessment of the early cellular membrane response to live Escherichia coli bacteremia. J Surg Res. 1989 Jan;46(1):9–15. doi: 10.1016/0022-4804(89)90175-3. [DOI] [PubMed] [Google Scholar]
  47. Tracey K. J., Lowry S. F., Beutler B., Cerami A., Albert J. D., Shires G. T. Cachectin/tumor necrosis factor mediates changes of skeletal muscle plasma membrane potential. J Exp Med. 1986 Oct 1;164(4):1368–1373. doi: 10.1084/jem.164.4.1368. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Tracey K. J., Lowry S. F., Fahey T. J., 3rd, Albert J. D., Fong Y., Hesse D., Beutler B., Manogue K. R., Calvano S., Wei H. Cachectin/tumor necrosis factor induces lethal shock and stress hormone responses in the dog. Surg Gynecol Obstet. 1987 May;164(5):415–422. [PubMed] [Google Scholar]
  49. Trivedi B., Danforth W. H. Effect of pH on the kinetics of frog muscle phosphofructokinase. J Biol Chem. 1966 Sep 10;241(17):4110–4112. [PubMed] [Google Scholar]
  50. Trunkey D. D., Illner H., Wagner I. Y., Shires G. T. The effect of septic shock on skeletal muscle action potentials in the primate. Surgery. 1979 Jun;85(6):638–643. [PubMed] [Google Scholar]
  51. Wichterman K. A., Baue A. E., Chaudry I. H. Sepsis and septic shock--a review of laboratory models and a proposal. J Surg Res. 1980 Aug;29(2):189–201. doi: 10.1016/0022-4804(80)90037-2. [DOI] [PubMed] [Google Scholar]
  52. Zentella A., Manogue K., Cerami A. Cachectin/TNF-mediated lactate production in cultured myocytes is linked to activation of a futile substrate cycle. Cytokine. 1993 Sep;5(5):436–447. doi: 10.1016/1043-4666(93)90033-2. [DOI] [PubMed] [Google Scholar]

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