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. 1990 Apr 1;95(4):591–616. doi: 10.1085/jgp.95.4.591

Relationships between the neuronal sodium/potassium pump and energy metabolism. Effects of K+, Na+, and adenosine triphosphate in isolated brain synaptosomes

PMCID: PMC2216333  PMID: 2159972

Abstract

The relationships between Na/K pump activity and adenosine triphosphate (ATP) production were determined in isolated rat brain synaptosomes. The activity of the enzyme was modulated by altering [K+]e, [Na+]i, and [ATP]i while synaptosomal oxygen uptake and lactate production were measured simultaneously. KCl increased respiration and glycolysis with an apparent Km of about 1 mM which suggests that, at the [K+]e normally present in brain, 3.3-4 mM, the pump is near saturation with this cation. Depolarization with 6-40 mM KCl had negligible effect on ouabain-sensitive O2 uptake indicating that at the voltages involved the activity of the Na/K ATPase is largely independent of membrane potential. Increases in [Na+]i by addition of veratridine markedly enhanced glycoside-inhibitable respiration and lactate production. Calculations of the rates of ATP synthesis necessary to support the operation of the pump showed that greater than 90% of the energy was derived from oxidative phosphorylation. Consistent with this: (a) the ouabain-sensitive Rb/O2 ratio was close to 12 (i.e., Rb/ATP ratio of 2); (b) inhibition of mitochondrial ATP synthesis by Amytal resulted in a decrease in the glycoside-dependent rate of 86Rb uptake. Analyses of the mechanisms responsible for activation of the energy-producing pathways during enhanced Na and K movements indicate that glycolysis is predominantly stimulated by increase in activity of phosphofructokinase mediated via a rise in the concentrations of adenosine monophosphate [AMP] and inorganic phosphate [Pi] and a fall in the concentration of phosphocreatine [PCr]; the main moving force for the elevation in mitochondrial ATP generation is the decline in [ATP]/[ADP] [Pi] (or equivalent) and consequent readjustments in the ratio of the intramitochondrial pyridine nucleotides [( NAD]m/[NADH]m). Direct stimulation of pyruvate dehydrogenase by calcium appears to be of secondary importance. It is concluded that synaptosomal Na/K pump is fueled primarily by oxidative phosphorylation and that a fall in [ATP]/[ADP][Pi] is the chief factor responsible for increased energy production.

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Selected References

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  1. Abdel-Latif A. A., Smith J. P., Hedrick N. Adenosinetriphosphatase and nucleotide metabolism in synaptosomes of rat brain. J Neurochem. 1970 Mar;17(3):391–401. doi: 10.1111/j.1471-4159.1970.tb02226.x. [DOI] [PubMed] [Google Scholar]
  2. Akera T., Ng Y. C., Shieh I. S., Bero E., Brody T. M., Braselton W. E. Effects of K+ on the interaction between cardiac glycosides and Na,K-ATPase. Eur J Pharmacol. 1985 May 8;111(2):147–157. doi: 10.1016/0014-2999(85)90751-4. [DOI] [PubMed] [Google Scholar]
  3. Ashley R. H., Brammer M. J., Marchbanks R. Measurement of intrasynaptosomal free calcium by using the fluorescent indicator quin-2. Biochem J. 1984 Apr 1;219(1):149–158. doi: 10.1042/bj2190149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Astrup J., Sørensen P. M., Sørensen H. R. Oxygen and glucose consumption related to Na+-K+ transport in canine brain. Stroke. 1981 Nov-Dec;12(6):726–730. doi: 10.1161/01.str.12.6.726. [DOI] [PubMed] [Google Scholar]
  5. Baker P. F. Phosphorus metabolism of intact crab nerve and its relation to the active transport of ions. J Physiol. 1965 Sep;180(2):383–423. doi: 10.1113/jphysiol.1965.sp007709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Blaustein M. P., Goldring J. M. Membrane potentials in pinched-off presynaptic nerve ternimals monitored with a fluorescent probe: evidence that synaptosomes have potassium diffusion potentials. J Physiol. 1975 Jun;247(3):589–615. doi: 10.1113/jphysiol.1975.sp010949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Booth R. F., Clark J. B. A rapid method for the preparation of relatively pure metabolically competent synaptosomes from rat brain. Biochem J. 1978 Nov 15;176(2):365–370. doi: 10.1042/bj1760365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Borgström L., Chapman A. G., Siesjö B. K. Glucose consumption in the cerebral cortex of rat during bicuculline-induced status epilipticus. J Neurochem. 1976 Oct;27(4):971–973. doi: 10.1111/j.1471-4159.1976.tb05165.x. [DOI] [PubMed] [Google Scholar]
  9. Brand M. D., Murphy M. P. Control of electron flux through the respiratory chain in mitochondria and cells. Biol Rev Camb Philos Soc. 1987 May;62(2):141–193. doi: 10.1111/j.1469-185x.1987.tb01265.x. [DOI] [PubMed] [Google Scholar]
  10. Brethes D., Dayanithi G., Letellier L., Nordmann J. J. Depolarization-induced Ca2+ increase in isolated neurosecretory nerve terminals measured with fura-2. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1439–1443. doi: 10.1073/pnas.84.5.1439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Browning M., Bennett W. F., Kelly P., Lynch G. Evidence that the 40,000 Mr phosphoprotein influenced by high frequency synaptic stimulation is the alpha subunit of pyruvate dehydrogenase. Brain Res. 1981 Aug 10;218(1-2):255–266. doi: 10.1016/0006-8993(81)91305-6. [DOI] [PubMed] [Google Scholar]
  12. Burke E. P., Reed J. B., Sanders K. M. Role of sodium pump in membrane potential gradient of canine proximal colon. Am J Physiol. 1988 Apr;254(4 Pt 1):C475–C483. doi: 10.1152/ajpcell.1988.254.4.C475. [DOI] [PubMed] [Google Scholar]
  13. Bührle C. P., Sonnhof U. The ionic mechanism of the excitatory action of glutamate upon the membranes of motoneurones of the frog. Pflugers Arch. 1983 Feb;396(2):154–162. doi: 10.1007/BF00615520. [DOI] [PubMed] [Google Scholar]
  14. Bünger R., Permanetter B. Parallel stimulation by Ca2+ of inotropism and pyruvate dehydrogenase in perfused heart. Am J Physiol. 1984 Jul;247(1 Pt 1):C45–C52. doi: 10.1152/ajpcell.1984.247.1.C45. [DOI] [PubMed] [Google Scholar]
  15. CHANCE B., WILLIAMS G. R. The respiratory chain and oxidative phosphorylation. Adv Enzymol Relat Subj Biochem. 1956;17:65–134. doi: 10.1002/9780470122624.ch2. [DOI] [PubMed] [Google Scholar]
  16. Capponi A. M., Lew P. D., Schlegel W., Pozzan T. Use of intracellular calcium and membrane potential fluorescent indicators in neuroendocrine cells. Methods Enzymol. 1986;124:116–135. doi: 10.1016/0076-6879(86)24012-4. [DOI] [PubMed] [Google Scholar]
  17. Chapman A. G., Meldrum B. S., Siesjö B. K. Cerebral metabolic changes during prolonged epileptic seizures in rats. J Neurochem. 1977 May;28(5):1025–1035. doi: 10.1111/j.1471-4159.1977.tb10665.x. [DOI] [PubMed] [Google Scholar]
  18. Claus T. H., Pilkis S. J. Effect of dichloroacetate and glucagon on the incorporation of labeled substrates into glucose and on pyruvate dehydrogenase in hepatocytes from fed and starved rats. Arch Biochem Biophys. 1977 Jul;182(1):52–63. doi: 10.1016/0003-9861(77)90282-x. [DOI] [PubMed] [Google Scholar]
  19. Collins R. C., Posner J. B., Plum F. Cerebral energy metabolism during electroshock seizures in mice. Am J Physiol. 1970 Apr;218(4):943–950. doi: 10.1152/ajplegacy.1970.218.4.943. [DOI] [PubMed] [Google Scholar]
  20. Dagani F., Erecińska M. Relationships among ATP synthesis, K+ gradients, and neurotransmitter amino acid levels in isolated rat brain synaptosomes. J Neurochem. 1987 Oct;49(4):1229–1240. doi: 10.1111/j.1471-4159.1987.tb10015.x. [DOI] [PubMed] [Google Scholar]
  21. Denton R. M., McCormack J. G. Ca2+ transport by mammalian mitochondria and its role in hormone action. Am J Physiol. 1985 Dec;249(6 Pt 1):E543–E554. doi: 10.1152/ajpendo.1985.249.6.E543. [DOI] [PubMed] [Google Scholar]
  22. Denton R. M., Randle P. J., Martin B. R. Stimulation by calcium ions of pyruvate dehydrogenase phosphate phosphatase. Biochem J. 1972 Jun;128(1):161–163. doi: 10.1042/bj1280161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Denton R. M., Richards D. A., Chin J. G. Calcium ions and the regulation of NAD+-linked isocitrate dehydrogenase from the mitochondria of rat heart and other tissues. Biochem J. 1978 Dec 15;176(3):899–906. doi: 10.1042/bj1760899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Diamond I., Fishman R. A. High-affinity transport and phosphorylation of 2-deoxy-D-glucose in synaptosomes. J Neurochem. 1973 Jun;20(6):1533–1542. doi: 10.1111/j.1471-4159.1973.tb00271.x. [DOI] [PubMed] [Google Scholar]
  25. Duffy T. E., Howse D. C., Plum F. Cerebral energy metabolism during experimental status epilepticus. J Neurochem. 1975 May;24(5):925–934. doi: 10.1111/j.1471-4159.1975.tb03657.x. [DOI] [PubMed] [Google Scholar]
  26. Erecińska M., Silver I. A. ATP and brain function. J Cereb Blood Flow Metab. 1989 Feb;9(1):2–19. doi: 10.1038/jcbfm.1989.2. [DOI] [PubMed] [Google Scholar]
  27. Erecińska M., Troeger M. B., Alston T. A. Amino acid neurotransmitters in the CNS: properties of diaminobutyric acid transport. J Neurochem. 1986 May;46(5):1452–1457. doi: 10.1111/j.1471-4159.1986.tb01761.x. [DOI] [PubMed] [Google Scholar]
  28. Erecińska M., Wilson D. F. Regulation of cellular energy metabolism. J Membr Biol. 1982;70(1):1–14. doi: 10.1007/BF01871584. [DOI] [PubMed] [Google Scholar]
  29. Erecińska M., Zaleska M. M., Nissim I., Nelson D., Dagani F., Yudkoff M. Glucose and synaptosomal glutamate metabolism: studies with [15N]glutamate. J Neurochem. 1988 Sep;51(3):892–902. doi: 10.1111/j.1471-4159.1988.tb01826.x. [DOI] [PubMed] [Google Scholar]
  30. Fein A., Tsacopoulos M. Activation of mitochondrial oxidative metabolism by calcium ions in Limulus ventral photoreceptor. Nature. 1988 Feb 4;331(6155):437–440. doi: 10.1038/331437a0. [DOI] [PubMed] [Google Scholar]
  31. Glynn I. M., Karlish S. J. The sodium pump. Annu Rev Physiol. 1975;37:13–55. doi: 10.1146/annurev.ph.37.030175.000305. [DOI] [PubMed] [Google Scholar]
  32. Grisar T., Frere J. M., Franck G. Effect of K+ ions on kinetic properties of the (Na+, K+)-ATPase (EC 3.6.1.3) of bulk isolated glial cells, perikarya and synaptosomes from rabbit brain cortex. Brain Res. 1979 Apr 6;165(1):87–103. doi: 10.1016/0006-8993(79)90047-7. [DOI] [PubMed] [Google Scholar]
  33. Hansen A. J. Effect of anoxia on ion distribution in the brain. Physiol Rev. 1985 Jan;65(1):101–148. doi: 10.1152/physrev.1985.65.1.101. [DOI] [PubMed] [Google Scholar]
  34. Hansford R. G., Castro F. Role of Ca2+ in pyruvate dehydrogenase interconversion in brain mitochondria and synaptosomes. Biochem J. 1985 Apr 1;227(1):129–136. doi: 10.1042/bj2270129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Hansford R. G. Relation between mitochondrial calcium transport and control of energy metabolism. Rev Physiol Biochem Pharmacol. 1985;102:1–72. doi: 10.1007/BFb0034084. [DOI] [PubMed] [Google Scholar]
  36. Harris S. I., Balaban R. S., Mandel L. J. Oxygen consumption and cellular ion transport: evidence for adenosine triphosphate to O2 ratio near 6 in intact cell. Science. 1980 Jun 6;208(4448):1148–1150. doi: 10.1126/science.6246581. [DOI] [PubMed] [Google Scholar]
  37. Ikehara T., Yamaguchi H., Hosokawa K., Sakai T., Miyamoto H. Rb+ influx in response to changes in energy generation: effect of the regulation of the ATP content of HeLa cells. J Cell Physiol. 1984 Jun;119(3):273–282. doi: 10.1002/jcp.1041190305. [DOI] [PubMed] [Google Scholar]
  38. 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]
  39. Kageyama G. H., Wong-Riley M. T. Histochemical localization of cytochrome oxidase in the hippocampus: correlation with specific neuronal types and afferent pathways. Neuroscience. 1982 Oct;7(10):2337–2361. doi: 10.1016/0306-4522(82)90199-3. [DOI] [PubMed] [Google Scholar]
  40. Kageyama G. H., Wong-Riley M. Laminar and cellular localization of cytochrome oxidase in the cat striate cortex. J Comp Neurol. 1986 Mar 8;245(2):137–159. doi: 10.1002/cne.902450202. [DOI] [PubMed] [Google Scholar]
  41. Katz L. A., Koretsky A. P., Balaban R. S. Activation of dehydrogenase activity and cardiac respiration: a 31P-NMR study. Am J Physiol. 1988 Jul;255(1 Pt 2):H185–H188. doi: 10.1152/ajpheart.1988.255.1.H185. [DOI] [PubMed] [Google Scholar]
  42. Kauppinen R. A., Nicholls D. G. Pyruvate utilization by synaptosomes is independent of calcium. FEBS Lett. 1986 Apr 21;199(2):222–226. doi: 10.1016/0014-5793(86)80484-7. [DOI] [PubMed] [Google Scholar]
  43. 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]
  44. Knull H. R. Association of glycolytic enzymes with particulate fractions from nerve endings. Biochim Biophys Acta. 1978 Jan 12;522(1):1–9. doi: 10.1016/0005-2744(78)90316-9. [DOI] [PubMed] [Google Scholar]
  45. Landowne D., Ritchie J. M. Optical studies on the kinetics of the sodium pump in mammalian non-myelinated nerve fibres. J Physiol. 1971 Jan;212(2):483–502. doi: 10.1113/jphysiol.1971.sp009337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Levinson C., Hempling H. G. The role of ion transport in the regulation of respiration in the Ehrlich mouse ascites-tumor cell. Biochim Biophys Acta. 1967 May 2;135(2):306–318. doi: 10.1016/0005-2736(67)90124-1. [DOI] [PubMed] [Google Scholar]
  47. Lewis D. V., Schuette W. H. NADH fluorescence, [K+]0 and oxygen consumption in cat cerebral cortex during direct cortical stimulation. Brain Res. 1976 Jul 16;110(3):523–535. doi: 10.1016/0006-8993(76)90863-5. [DOI] [PubMed] [Google Scholar]
  48. Lim L., Hall C., Leung T., Mahadevan L., Whatley S. Neurone-specific enolase and creatine phosphokinase are protein components of rat brain synaptic plasma membranes. J Neurochem. 1983 Oct;41(4):1177–1182. doi: 10.1111/j.1471-4159.1983.tb09069.x. [DOI] [PubMed] [Google Scholar]
  49. 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]
  50. Logan J. G. The extrusion of sodium ions from presynaptic nerve endings of rat cerebral cortex. J Neurochem. 1980 Aug;35(2):349–353. doi: 10.1111/j.1471-4159.1980.tb06271.x. [DOI] [PubMed] [Google Scholar]
  51. Lothman E., Lamanna J., Cordingley G., Rosenthal M., Somjen G. Responses of electrical potential, potassium levels, and oxidative metabolic activity of the cerebral neocortex of cats. Brain Res. 1975 Apr 25;88(1):15–36. doi: 10.1016/0006-8993(75)90943-9. [DOI] [PubMed] [Google Scholar]
  52. 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]
  53. McCormack J. G., Denton R. M. The effects of calcium ions and adenine nucleotides on the activity of pig heart 2-oxoglutarate dehydrogenase complex. Biochem J. 1979 Jun 15;180(3):533–544. doi: 10.1042/bj1800533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. McCormack J. G., England P. J. Ruthenium Red inhibits the activation of pyruvate dehydrogenase caused by positive inotropic agents in the perfused rat heart. Biochem J. 1983 Aug 15;214(2):581–585. doi: 10.1042/bj2140581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Meyer R. A., Sweeney H. L., Kushmerick M. J. A simple analysis of the "phosphocreatine shuttle". Am J Physiol. 1984 May;246(5 Pt 1):C365–C377. doi: 10.1152/ajpcell.1984.246.5.C365. [DOI] [PubMed] [Google Scholar]
  56. Michenfelder J. D. The interdependency of cerebral functional and metabolic effects following massive doses of thiopental in the dog. Anesthesiology. 1974 Sep;41(3):231–236. doi: 10.1097/00000542-197409000-00004. [DOI] [PubMed] [Google Scholar]
  57. Moore C. L. Specific inhibition of mitochondrial Ca++ transport by ruthenium red. Biochem Biophys Res Commun. 1971 Jan 22;42(2):298–305. doi: 10.1016/0006-291x(71)90102-1. [DOI] [PubMed] [Google Scholar]
  58. Moreno-Sánchez R., Hansford R. G. Relation between cytosolic free calcium and respiratory rates in cardiac myocytes. Am J Physiol. 1988 Aug;255(2 Pt 2):H347–H357. doi: 10.1152/ajpheart.1988.255.2.H347. [DOI] [PubMed] [Google Scholar]
  59. Nicholson C., ten Bruggencate G., Stöckle H., Steinberg R. Calcium and potassium changes in extracellular microenvironment of cat cerebellar cortex. J Neurophysiol. 1978 Jul;41(4):1026–1039. doi: 10.1152/jn.1978.41.4.1026. [DOI] [PubMed] [Google Scholar]
  60. Pastuszko A., Wilson D. F., Erecińska M., Silver I. A. Effects of in vitro hypoxia and lowered pH on potassium fluxes and energy metabolism in rat brain synaptosomes. J Neurochem. 1981 Jan;36(1):116–123. doi: 10.1111/j.1471-4159.1981.tb02385.x. [DOI] [PubMed] [Google Scholar]
  61. 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]
  62. Pech I. V., Stahl W. L. Immunocytochemical localization of NA+, K+-ATPase in primary cultures of rat retina. Neurochem Res. 1984 Jun;9(6):757–769. doi: 10.1007/BF00965664. [DOI] [PubMed] [Google Scholar]
  63. Raffin C. N., Sick T. J., Rosenthal M. Inhibition of glycolysis alters potassium ion transport and mitochondrial redox activity in rat brain. J Cereb Blood Flow Metab. 1988 Dec;8(6):857–865. doi: 10.1038/jcbfm.1988.143. [DOI] [PubMed] [Google Scholar]
  64. Richards C. D., Metcalfe J. C., Smith G. A., Hesketh T. R. Changes in free-calcium levels and pH in synaptosomes during transmitter release. Biochim Biophys Acta. 1984 Apr 16;803(4):215–220. doi: 10.1016/0167-4889(84)90110-1. [DOI] [PubMed] [Google Scholar]
  65. Ritchie J. M. The oxygen consumption of mammalian non-myelinated nerve fibres at rest and during activity. J Physiol. 1967 Feb;188(3):309–329. doi: 10.1113/jphysiol.1967.sp008141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Robinson J. D. Substrate sites for the (Na+ + K+)-dependent ATPase. Biochim Biophys Acta. 1976 May 13;429(3):1006–1019. doi: 10.1016/0005-2744(76)90345-4. [DOI] [PubMed] [Google Scholar]
  67. SKOU J. C. ENZYMATIC BASIS FOR ACTIVE TRANSPORT OF NA+ AND K+ ACROSS CELL MEMBRANE. Physiol Rev. 1965 Jul;45:596–617. doi: 10.1152/physrev.1965.45.3.596. [DOI] [PubMed] [Google Scholar]
  68. SKOU J. C. The influence of some cations on an adenosine triphosphatase from peripheral nerves. Biochim Biophys Acta. 1957 Feb;23(2):394–401. doi: 10.1016/0006-3002(57)90343-8. [DOI] [PubMed] [Google Scholar]
  69. Schaffer W. T., Olson M. S. The regulation of pyruvate oxidation during membrane depolarization of rat brain synaptosomes. Biochem J. 1980 Nov 15;192(2):741–751. doi: 10.1042/bj1920741. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Schurr A., West C. A., Rigor B. M. Lactate-supported synaptic function in the rat hippocampal slice preparation. Science. 1988 Jun 3;240(4857):1326–1328. doi: 10.1126/science.3375817. [DOI] [PubMed] [Google Scholar]
  71. Schwartz W. J., Sharp F. R. Autoradiographic maps of regional brain glucose consumption in resting, awake rats using (14C) 2-deoxyglucose. J Comp Neurol. 1978 Jan 15;177(2):335–359. doi: 10.1002/cne.901770210. [DOI] [PubMed] [Google Scholar]
  72. Scott I. D., Nicholls D. G. Energy transduction in intact synaptosomes. Influence of plasma-membrane depolarization on the respiration and membrane potential of internal mitochondria determined in situ. Biochem J. 1980 Jan 15;186(1):21–33. doi: 10.1042/bj1860021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Sejersted O. M., Wasserstrom J. A., Fozzard H. A. Na,K pump stimulation by intracellular Na in isolated, intact sheep cardiac Purkinje fibers. J Gen Physiol. 1988 Mar;91(3):445–466. doi: 10.1085/jgp.91.3.445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. Shank R. P., Bennett G. S., Freytag S. O., Campbell G. L. Pyruvate carboxylase: an astrocyte-specific enzyme implicated in the replenishment of amino acid neurotransmitter pools. Brain Res. 1985 Mar 11;329(1-2):364–367. doi: 10.1016/0006-8993(85)90552-9. [DOI] [PubMed] [Google Scholar]
  75. Shirachi D. Y., Allard A. A., Trevor A. J. Partial purification and ouabain sensitivity of Lubrol-extracted sodium-potassium transport adenosine triphosphatases from brain and cardiac tissues. Biochem Pharmacol. 1970 Nov;19(11):2893–2906. doi: 10.1016/0006-2952(70)90028-6. [DOI] [PubMed] [Google Scholar]
  76. Soltoff S. P., Mandel L. J. Active ion transport in the renal proximal tubule. III. The ATP dependence of the Na pump. J Gen Physiol. 1984 Oct;84(4):643–662. doi: 10.1085/jgp.84.4.643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. Somjen G. G. Extracellular potassium in the mammalian central nervous system. Annu Rev Physiol. 1979;41:159–177. doi: 10.1146/annurev.ph.41.030179.001111. [DOI] [PubMed] [Google Scholar]
  78. Sweadner K. J. Enzymatic properties of separated isozymes of the Na,K-ATPase. Substrate affinities, kinetic cooperativity, and ion transport stoichiometry. J Biol Chem. 1985 Sep 25;260(21):11508–11513. [PubMed] [Google Scholar]
  79. Tessitore N., Sakhrani L. M., Massry S. G. Quantitative requirement for ATP for active transport in isolated renal cells. Am J Physiol. 1986 Jul;251(1 Pt 1):C120–C127. doi: 10.1152/ajpcell.1986.251.1.C120. [DOI] [PubMed] [Google Scholar]
  80. Tsien R. Y., Pozzan T., Rink T. J. Calcium homeostasis in intact lymphocytes: cytoplasmic free calcium monitored with a new, intracellularly trapped fluorescent indicator. J Cell Biol. 1982 Aug;94(2):325–334. doi: 10.1083/jcb.94.2.325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  81. Ulbricht W. The effect of veratridine on excitable membranes of nerve and muscle. Ergeb Physiol. 1969;61:18–71. doi: 10.1007/BFb0111446. [DOI] [PubMed] [Google Scholar]
  82. Urayama O., Nakao M. Organ secificity of rat sodium- and potassium-activated adenosine triphosphatase. J Biochem. 1979 Nov;86(5):1371–1381. doi: 10.1093/oxfordjournals.jbchem.a132654. [DOI] [PubMed] [Google Scholar]
  83. WHITTAM R. Active cation transport as a pace-maker of respiration. Nature. 1961 Aug 5;191:603–604. doi: 10.1038/191603a0. [DOI] [PubMed] [Google Scholar]
  84. Weiss J., Hiltbrand B. Functional compartmentation of glycolytic versus oxidative metabolism in isolated rabbit heart. J Clin Invest. 1985 Feb;75(2):436–447. doi: 10.1172/JCI111718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  85. Yingst D. R. Modulation of the Na,K-ATPase by Ca and intracellular proteins. Annu Rev Physiol. 1988;50:291–303. doi: 10.1146/annurev.ph.50.030188.001451. [DOI] [PubMed] [Google Scholar]

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