Skip to main content
Log in

Na+,K+-ATPase in developing fetal guinea pig brain and the effect of maternal hypoxia

  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Na+,K+-ATPase activity was determined in fetal guinea pig brain at 35, 40, 45, 50, 55, and 60 days of gestation. The activity remained at a constant level during the early periods (35–45 days) of gestation and increased significantly during 45–60 days. Following maternal hypoxia, the activity of Na+,K+-ATPase in the term (60 days) fetal brain was reduced by 50% whereas the preterm (50 days) brain activity was unaffected. Under identical hypoxic conditions, the enzymatic activity of adult brain was significantly reduced by 20%. Na+,K+-ATPase obtained from fetal brain (50 days of gestation) has both a low and a high affinity for ATP (K m values =0.50 and 0.053 mM and correspondingV max values =10.77 and 2.82 umoles Pi/mg protein/hr), whereas the enzyme in the adult brain has only a low affinity (K m=1.67 mM andV max=20.32 umoles Pi/mg protein/hr). The high and low affinity sites for ATP in the fetal brain suggests a mechanism essential for the maintenance of cellular ionic gradients at low concentrations of ATP and which would provide the fetal brain with a greater tolerance to hypoxia. The high sensitivity of Na+,K+-ATPase activity to hypoxia in guinea pig brain at term suggests that the cell membrane functions of the fetal brain may be more susceptible to hypoxia at term than it is earlier in gestation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Alberts, R. W., Rodriguez de Lores Arnaiz, G., and De Robertis, E. 1965. Sodium-Potassium activated and Potassium activated p-nitrophenyl phosphatase: A comparison of their subcellular localization in rat brain Proc. Nat'l. Acad. Sci. 53:557–564.

    Google Scholar 

  2. Banns, H., Blatehford, D., and Holzbauer, M. 1980. The development of Monoamine oxidase, glutamate-dicarboxylase and choline Acetyl-transferase in the guinea pig brain. J. Neural Transmission 49:21–30.

    Google Scholar 

  3. Booth, R. F. G., Patel, T. B., and Clark, J. B. 1980. The development of enzymes of energy metabolism in brain of a precocial (guinea pig) and noncocial (rat) species. J. Neurochem. 43:327–366.

    Google Scholar 

  4. Chan, H. W. S., and Levett, A. 1977. Autoxidation of methyl linoleate separation and analysis of isomer mixtures of methyl linoleate hydroperoxide and methylhydroxylinoleates. Lipids 12:99–106.

    Google Scholar 

  5. Crawford, M. A., and Sinclair, A. J. 1972. Nutritional influences in the evolution of mammalian brain. Pages 267–292,in Lipids, Malnutrition, and the Developing Brain. Ciba Foundation Symposia (Associated Scientific Publishers).

  6. Dahl, J. L., and Hokian, L. E. 1974. The sodium potassium adenosine triphosphatase. Ann. Rev. Biochem. 43:327–366.

    Google Scholar 

  7. Dobbing, J. 1974. The later growth of brain and its vulnerability. Pediatrics 53:2–6.

    Google Scholar 

  8. Dobbing, J., and Sands, J. 1970. Growth and development of the brain and spinal cord of the guinea pig. Brain Res. 17:115–123.

    Google Scholar 

  9. Fiske, C. H., and Subbarow, Y. 1925. The colorimetric determination of phosphorus. J. Biol. Chem. 66:375–400.

    Google Scholar 

  10. Flexner, L. B. 1955. Enzymatic and functional patterns of developing mammalian brain. Pages 281–295,in Waelsch H, (ed.). Biochemistry of the Developing Nervous System. Academic Press, New York.

    Google Scholar 

  11. Folch-Pi, J., Lees, M. J., and Sloane-Stanley, G. H. 1957. A simple method for the isolation and purification of total lipids from animal tissue. J. Biol. Chem. 226:497–409.

    Google Scholar 

  12. Frank, L. 1982. Protection from O2 toxicity by pre-exposure to hypoxia: lung antioxidant enzyme role. J. Appl. Physiol. 53:475–482.

    Google Scholar 

  13. Fridovich, I. 1978 Hypoxia and oxygen toxicity. Adv. Neurol. 26:255–259.

    Google Scholar 

  14. Goldberg, W. J., Watson, B. D., Busto, R., Kurchner, H., Santiso, M., and Ginsburg, M. D. 1984. Concurrent measurement of (Na+,K+)-ATPase activity and lipid peroxides in rat brain following reversible global ischemia. Neurochem. Res. 9:1737–1747.

    Google Scholar 

  15. Goldman, S. S., and Albers, R. W. 1973. Sodium-potassium activated adenosine triphosphate. IX: The role of phospholipids. J. Biol. Chem. 248:867–874.

    Google Scholar 

  16. Hexum, T. D., and Fried, R. 1979. Effect of superoxide radicals on Na+K) transport adenosine triphosphatase and protection by superoxide dismutase. Neurochem. Res. 4:73–92.

    Google Scholar 

  17. Himwich, H. E. 1951. Brain Metabolism and Cerebral Disorders. Williams and Wilkins, Baltimore.

    Google Scholar 

  18. Himwich, W. A. 1962 Biochemical and neurophysiological development of the brain in the neonatal period. Pages 117–158, In (Pfeiffer, C. S. and Smith, J. R., eds.),International Review of Neurobiology, vol. 4. Academic Press, New York.

    Google Scholar 

  19. Imaizumi, S., Kayama, T., and Suzuki, J. 1984 Chemiluminescence in hyopxic brain-the first report. Correlation between energy metabolism and free radical reaction.Stroke 15:1061–1065.

    Google Scholar 

  20. Jorgensen, P. L. 1982. Mechanism of the Na+,K+ pump protein structure and conformations of the pure (Na+,K+)-ATPase. Biochem. biophys. Acta 694:27–68.

    Google Scholar 

  21. Kovachich, G. B., and Mishra, O. P. 1981. Partial inactivation of Na+,K+-ATPase in cortical brain slices incubated in normal Krebs-Ringer phosphate medium at 1 and 10 atm oxygen pressures. J. Neurochem. 36:333–335.

    Google Scholar 

  22. Lowry, O. H., Rosenbrough, N. J., Farr, A. L., and Randall, R. J. 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193:265–275.

    Google Scholar 

  23. Mishra, O. P., and Shankar, R. 1980 Na+,K+-ATPase in developing rat brain during undernutrition. Nutr. Metab. 24:114–121.

    Google Scholar 

  24. Mishra, O. P., and Delivoria-Papadopoulos, M. 1986 Na+,K+-ATPase in the developing brain of fetal guinea pigs during normoxia and hypoxia. Proceedings of the 16th annual meeting of the Society for Neuroscience, Washington.

  25. Naguchi, T., and Freed, S. 1971 Dissociation of lipid components and reconstitution at −75°C Mg2+ dependent, Na+ and K+ stimulated, adenosine triphosphatase in rat brain. Nature New Biol. 230:148–150.

    Google Scholar 

  26. Samson, F. E., and Quin, D. J. 1967 Na+,K+-activated ATPase in rat brain during development. J. Neurochem. 14:421–427.

    Google Scholar 

  27. Schade, J. P., and Baxter, C. F. 1960. Changes during growth in the volume and surface area of cortical neurons in rabbit. Exp. Neurol. 2:158–178.

    Google Scholar 

  28. Schaefer, A., Komlos, M., and Seregi, A. 1975. Lipid peroxidation as the cause of the ascorbic acid induced decrease of adenosine triphosphatase activities of rat brain microsomes and its inhibition by biogenic amines and psychotropic drugs. Biochem. Pharmacol. 24:1781–1786.

    Google Scholar 

  29. Skou, J. C. 1957. The influence of some cations on an adenosine triphosphatase from peripheral nerves. Biochim. Biophys. Acta 23:394–401.

    Google Scholar 

  30. Skou, J. C. 1965. Enzymatic basis for active transport of Na+ and K+ across cell membrane. Physiol Rev. 45:596–617.

    Google Scholar 

  31. Smith, D. S., Rosenthal, M., Nioka, S., Subramanian, H., and Chance, B. 1986 Brain cytochromes and changes in brain energy states. Society of Magnetic Resonance (Abstract) 4:1113–1114.

    Google Scholar 

  32. Smith, D. S. 1986 Barbiturates as free radical scavengers and protective agents in brain ischemia. In Free Radicals Aging and Degenerative Diseases (Johnson, J. E. Jr., ed) Alan R. Liss Inc. pp. 457–480.

  33. Specht, S. C. 1984. Development and regional distribution of two molecular forms of the catalytic subunit of the Na-K-ATPase in rat brain. Biochem. Biophys. Res. Comm. 121:208–212.

    Google Scholar 

  34. Stahl, W. L. and Albers, R. W. 1986. The Na,K-ATPase of nervous tissue, Neurochem. Int. 8:449–476.

    Google Scholar 

  35. Sun, A. Y. 1972. The effect of lipoxidation on synaptosomal (Na+K+)-ATPase isolated from the cerebral cortex of squirrel monkey. Biochim. Biophys. Acta 266:350–360.

    Google Scholar 

  36. Sun, G. Y., and Sun, A. Y. 1974. Synaptosomal plasma membrane: acyl group composition of phosphoglycerides and Na+,K+-ATPase activity during fatty acid deficiency. J. Neurochem. 22:15–18.

    Google Scholar 

  37. Sweadner, K. J. 1979. Two molecular forms of (Na+K+)-stimulated ATPase in brain: separation and difference in affinity for strophanthidin. J. Biol. Chem. 254:6060–6067.

    Google Scholar 

  38. Tanaguchi, K., and Tonomura, Y. 1971. Inactivation of Na+,K+-dependent ATPase by phospholipase treatment and its reactivation by phospholipids. J. Biochem. (Tokyo) 69:543–550.

    Google Scholar 

  39. Tanaka, R. 1974. The role of lipids in activation of Na,K dependent ATPase and K dependent phosphatase of the brain. Pages 181–234,in Ehrenpreis, S. and Kopin, J., (eds.), Review of Neuroscience Vol. 1, Raven Press, New York.

    Google Scholar 

  40. Wells, M. A., and Ditmar, J. C. 1967. A comprehensive study of the postnatal changes in the concentration of the lipids of developing rat brain. Biochemistry 6:3169–3175.

    Google Scholar 

  41. Wheeler, K. P., Walker, J. A., and Baker, D. M. 1975. Lipid requirement of the membrane sodium-plus-potassium ion-dependent adenosine triphosphate system. Biochem. J. 146:711–722.

    Google Scholar 

  42. Wilson, W. E. 1980. A comparison of Na+-K+-ATPases obtained from brains of adult and fetal rats. Int. J. Biochem. 12:379–385.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mishra, O.P., Delivoria-Papadopoulos, M. Na+,K+-ATPase in developing fetal guinea pig brain and the effect of maternal hypoxia. Neurochem Res 13, 765–770 (1988). https://doi.org/10.1007/BF00971600

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00971600

Key Words