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. 1995 May 9;92(10):4616–4620. doi: 10.1073/pnas.92.10.4616

Role of sodium and potassium ions in regulation of glucose metabolism in cultured astroglia.

S Takahashi 1, B F Driscoll 1, M J Law 1, L Sokoloff 1
PMCID: PMC41995  PMID: 7753851

Abstract

Effects of increasing extracellular K+ or intracellular Na+ concentrations on glucose metabolism in cultures of rat astroglia and neurons were examined. Cells were incubated in bicarbonate buffer, pH 7.2, containing 2 mM glucose, tracer amounts of [14C]deoxyglucose ([14C]dGlc), and 5.4, 28, or 56 mM KCl for 10, 15, or 30 min, and then for 5 min in [14C]dGlc-free buffer to allow efflux of unmetabolized [14C]dGlc. Cells were then digested and assayed for labeled products, which were shown to consist of 96-98% [14C]deoxyglucose 6-phosphate. Increased K+ concentrations significantly raised [14C]deoxyglucose 6-phosphate accumulation in both neuronal and mixed neuronal-astroglial cultures at 15 and 30 min but did not raise it in astroglial cultures. Veratridine (75 microM), which opens voltage-dependent Na+ channels, significantly raised rates of [14C]dGlc phosphorylation in astroglial cultures (+20%), and these elevations were blocked by either 1 mM ouabain, a specific inhibitor of Na+,K(+)-ATPase (EC 3.6.1.37), or 10 microM tetrodotoxin, which blocks Na+ channels. The carboxylic sodium ionophore, monensin (10 microM), more than doubled [14C]dGlc phosphorylation; this effect was only partially blocked by ouabain and unaffected by tetrodotoxin. L-Glutamate (500 microM) also stimulated [14C]dGlc phosphorylation in astroglia--not through N-methyl-D-aspartate or non-N-methyl-D-aspartate receptor mechanisms but via a Na(+)-dependent glutamate-uptake system. These results indicate that increased uptake of Na+ can stimulate energy metabolism in astroglial cells.

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Selected References

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  1. Badar-Goffer R. S., Ben-Yoseph O., Bachelard H. S., Morris P. G. Neuronal-glial metabolism under depolarizing conditions. A 13C-n.m.r. study. Biochem J. 1992 Feb 15;282(Pt 1):225–230. doi: 10.1042/bj2820225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barres B. A., Chun L. L., Corey D. P. Glial and neuronal forms of the voltage-dependent sodium channel: characteristics and cell-type distribution. Neuron. 1989 Apr;2(4):1375–1388. doi: 10.1016/0896-6273(89)90076-7. [DOI] [PubMed] [Google Scholar]
  3. Barres B. A. New roles for glia. J Neurosci. 1991 Dec;11(12):3685–3694. doi: 10.1523/JNEUROSCI.11-12-03685.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bowman C. L., Kimelberg H. K. Excitatory amino acids directly depolarize rat brain astrocytes in primary culture. Nature. 1984 Oct 18;311(5987):656–659. doi: 10.1038/311656a0. [DOI] [PubMed] [Google Scholar]
  5. Brines M. L., Robbins R. J. Cell-type specific expression of Na+, K(+)-ATPase catalytic subunits in cultured neurons and glia: evidence for polarized distribution in neurons. Brain Res. 1993 Dec 17;631(1):1–11. doi: 10.1016/0006-8993(93)91179-v. [DOI] [PubMed] [Google Scholar]
  6. Brookes N., Yarowsky P. J. Determinants of deoxyglucose uptake in cultured astrocytes: the role of the sodium pump. J Neurochem. 1985 Feb;44(2):473–479. doi: 10.1111/j.1471-4159.1985.tb05438.x. [DOI] [PubMed] [Google Scholar]
  7. Catterall W. A. Cellular and molecular biology of voltage-gated sodium channels. Physiol Rev. 1992 Oct;72(4 Suppl):S15–S48. doi: 10.1152/physrev.1992.72.suppl_4.S15. [DOI] [PubMed] [Google Scholar]
  8. Cummins C. J., Glover R. A., Sellinger O. Z. Astroglial uptake is modulated by extracellular K+. J Neurochem. 1979 Sep;33(3):779–785. doi: 10.1111/j.1471-4159.1979.tb05224.x. [DOI] [PubMed] [Google Scholar]
  9. Cummins C. J., Glover R. A., Sellinger O. Z. Neuronal cues regulate uptake in cultured astrocytes. Brain Res. 1979 Jul 6;170(1):190–193. doi: 10.1016/0006-8993(79)90953-3. [DOI] [PubMed] [Google Scholar]
  10. Danias P., Nicklas W. J., Ofori S., Shen J., Mytilineou C. Mesencephalic dopamine neurons become less sensitive to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity during development in vitro. J Neurochem. 1989 Oct;53(4):1149–1155. doi: 10.1111/j.1471-4159.1989.tb07408.x. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Erecińska M., Silver I. A. Ions and energy in mammalian brain. Prog Neurobiol. 1994 May;43(1):37–71. doi: 10.1016/0301-0082(94)90015-9. [DOI] [PubMed] [Google Scholar]
  13. Flott B., Seifert W. Characterization of glutamate uptake systems in astrocyte primary cultures from rat brain. Glia. 1991;4(3):293–304. doi: 10.1002/glia.440040307. [DOI] [PubMed] [Google Scholar]
  14. Hatten M. E. Neuronal regulation of astroglial morphology and proliferation in vitro. J Cell Biol. 1985 Feb;100(2):384–396. doi: 10.1083/jcb.100.2.384. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Henn F. A., Haljamäe H., Hamberger A. Glial cell function: active control of extracellular K + concentration. Brain Res. 1972 Aug 25;43(2):437–443. doi: 10.1016/0006-8993(72)90399-x. [DOI] [PubMed] [Google Scholar]
  16. Hertz L. An intense potassium uptake into astrocytes, its further enhancement by high concentrations of potassium, and its possible involvement in potassium homeostasis at the cellular level. Brain Res. 1978 Apr 21;145(1):202–208. doi: 10.1016/0006-8993(78)90812-0. [DOI] [PubMed] [Google Scholar]
  17. Hertz L. Drug-induced alterations of ion distribution at the cellular level of the central nervous system. Pharmacol Rev. 1977 Mar;29(1):35–65. [PubMed] [Google Scholar]
  18. Hertz L. Features of astrocytic function apparently involved in the response of central nervous tissue to ischemia-hypoxia. J Cereb Blood Flow Metab. 1981;1(2):143–153. doi: 10.1038/jcbfm.1981.17. [DOI] [PubMed] [Google Scholar]
  19. Hertz L., Peng L. Energy metabolism at the cellular level of the CNS. Can J Physiol Pharmacol. 1992;70 (Suppl):S145–S157. doi: 10.1139/y92-256. [DOI] [PubMed] [Google Scholar]
  20. Hisanaga K., Sagar S. M., Hicks K. J., Swanson R. A., Sharp F. R. c-fos proto-oncogene expression in astrocytes associated with differentiation or proliferation but not depolarization. Brain Res Mol Brain Res. 1990 Jun;8(1):69–75. doi: 10.1016/0169-328x(90)90011-2. [DOI] [PubMed] [Google Scholar]
  21. Kadekaro M., Crane A. M., Sokoloff L. Differential effects of electrical stimulation of sciatic nerve on metabolic activity in spinal cord and dorsal root ganglion in the rat. Proc Natl Acad Sci U S A. 1985 Sep;82(17):6010–6013. doi: 10.1073/pnas.82.17.6010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kai Kai M. A., Pentreath V. W. High resolution analysis of [3H]2-deoxyglucose incorporation into neurons and glial cells in invertebrate ganglia: histological processing of nervous tissue for selective marking of glycogen. J Neurocytol. 1981 Aug;10(4):693–708. doi: 10.1007/BF01262598. [DOI] [PubMed] [Google Scholar]
  23. Kanai Y., Hediger M. A. Primary structure and functional characterization of a high-affinity glutamate transporter. Nature. 1992 Dec 3;360(6403):467–471. doi: 10.1038/360467a0. [DOI] [PubMed] [Google Scholar]
  24. Kimelberg H. K., Biddelcome S., Narumi S., Bourke R. S. ATPase and carbonic anhydrase activities of bulk-isolated neuron, glia and synaptosome fractions from rat brain. Brain Res. 1978 Feb 10;141(2):305–323. doi: 10.1016/0006-8993(78)90200-7. [DOI] [PubMed] [Google Scholar]
  25. Li P. P., White T. D. Rapid effects of veratridine, tetrodotoxin, gramicidin D, valinomycin and NaCN on the Na+, K+ and ATP contents of synaptosomes. J Neurochem. 1977 May;28(5):967–975. doi: 10.1111/j.1471-4159.1977.tb10658.x. [DOI] [PubMed] [Google Scholar]
  26. Mata M., Fink D. J., Gainer H., Smith C. B., Davidsen L., Savaki H., Schwartz W. J., Sokoloff L. Activity-dependent energy metabolism in rat posterior pituitary primarily reflects sodium pump activity. J Neurochem. 1980 Jan;34(1):213–215. doi: 10.1111/j.1471-4159.1980.tb04643.x. [DOI] [PubMed] [Google Scholar]
  27. Medzihradsky F., Nandhasri P. S., Idoyaga-Vargas V., Sellinger O. Z. A comparison of ATPase activity of the glial cell fraction and the neuronal perikaryal fraction isolated in bulk from rat cerebbral cortex. J Neurochem. 1971 Aug;18(8):1599–1603. doi: 10.1111/j.1471-4159.1971.tb00023.x. [DOI] [PubMed] [Google Scholar]
  28. Orkand R. K., Nicholls J. G., Kuffler S. W. Effect of nerve impulses on the membrane potential of glial cells in the central nervous system of amphibia. J Neurophysiol. 1966 Jul;29(4):788–806. doi: 10.1152/jn.1966.29.4.788. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. Peng L., Zhang X., Hertz L. High extracellular potassium concentrations stimulate oxidative metabolism in a glutamatergic neuronal culture and glycolysis in cultured astrocytes but have no stimulatory effect in a GABAergic neuronal culture. Brain Res. 1994 Nov 7;663(1):168–172. doi: 10.1016/0006-8993(94)90475-8. [DOI] [PubMed] [Google Scholar]
  31. Pentreath V. W., Kai-Kai M. A. Significance of the potassium signal from neurones to glial cells. Nature. 1982 Jan 7;295(5844):59–61. doi: 10.1038/295059a0. [DOI] [PubMed] [Google Scholar]
  32. Pines G., Danbolt N. C., Bjørås M., Zhang Y., Bendahan A., Eide L., Koepsell H., Storm-Mathisen J., Seeberg E., Kanner B. I. Cloning and expression of a rat brain L-glutamate transporter. Nature. 1992 Dec 3;360(6403):464–467. doi: 10.1038/360464a0. [DOI] [PubMed] [Google Scholar]
  33. Pressman B. C., Fahim M. Pharmacology and toxicology of the monovalent carboxylic ionophores. Annu Rev Pharmacol Toxicol. 1982;22:465–490. doi: 10.1146/annurev.pa.22.040182.002341. [DOI] [PubMed] [Google Scholar]
  34. Rothstein J. D., Martin L., Levey A. I., Dykes-Hoberg M., Jin L., Wu D., Nash N., Kuncl R. W. Localization of neuronal and glial glutamate transporters. Neuron. 1994 Sep;13(3):713–725. doi: 10.1016/0896-6273(94)90038-8. [DOI] [PubMed] [Google Scholar]
  35. Shapiro D. L. Morphological and biochemical alterations in foetal rat brain cells cultured in the presence of monobutyryl cyclic AMP. Nature. 1973 Jan 19;241(5386):203–204. doi: 10.1038/241203a0. [DOI] [PubMed] [Google Scholar]
  36. Smith P. K., Krohn R. I., Hermanson G. T., Mallia A. K., Gartner F. H., Provenzano M. D., Fujimoto E. K., Goeke N. M., Olson B. J., Klenk D. C. Measurement of protein using bicinchoninic acid. Anal Biochem. 1985 Oct;150(1):76–85. doi: 10.1016/0003-2697(85)90442-7. [DOI] [PubMed] [Google Scholar]
  37. Sokoloff L. Localization of functional activity in the central nervous system by measurement of glucose utilization with radioactive deoxyglucose. J Cereb Blood Flow Metab. 1981;1(1):7–36. doi: 10.1038/jcbfm.1981.4. [DOI] [PubMed] [Google Scholar]
  38. Sokoloff L., Reivich M., Kennedy C., Des Rosiers M. H., Patlak C. S., Pettigrew K. D., Sakurada O., Shinohara M. The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J Neurochem. 1977 May;28(5):897–916. doi: 10.1111/j.1471-4159.1977.tb10649.x. [DOI] [PubMed] [Google Scholar]
  39. Sokoloff L. Sites and mechanisms of function-related changes in energy metabolism in the nervous system. Dev Neurosci. 1993;15(3-5):194–206. doi: 10.1159/000111335. [DOI] [PubMed] [Google Scholar]
  40. Somjen G. G. Electrophysiology of neuroglia. Annu Rev Physiol. 1975;37:163–190. doi: 10.1146/annurev.ph.37.030175.001115. [DOI] [PubMed] [Google Scholar]
  41. Storck T., Schulte S., Hofmann K., Stoffel W. Structure, expression, and functional analysis of a Na(+)-dependent glutamate/aspartate transporter from rat brain. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10955–10959. doi: 10.1073/pnas.89.22.10955. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Thio C. L., Waxman S. G., Sontheimer H. Ion channels in spinal cord astrocytes in vitro. III. Modulation of channel expression by coculture with neurons and neuron-conditioned medium. J Neurophysiol. 1993 Mar;69(3):819–831. doi: 10.1152/jn.1993.69.3.819. [DOI] [PubMed] [Google Scholar]
  43. 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]
  44. Yarowsky P., Boyne A. F., Wierwille R., Brookes N. Effect of monensin on deoxyglucose uptake in cultured astrocytes: energy metabolism is coupled to sodium entry. J Neurosci. 1986 Mar;6(3):859–866. doi: 10.1523/JNEUROSCI.06-03-00859.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Yarowsky P., Kadekaro M., Sokoloff L. Frequency-dependent activation of glucose utilization in the superior cervical ganglion by electrical stimulation of cervical sympathetic trunk. Proc Natl Acad Sci U S A. 1983 Jul;80(13):4179–4183. doi: 10.1073/pnas.80.13.4179. [DOI] [PMC free article] [PubMed] [Google Scholar]

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