, Volume 71, Issue 2, pp 159–163 | Cite as

The influence of external sodium and potassium on lithium uptake by primary brain cell cultures at ‘therapeutic’ lithium concentration

  • Z. Janka
  • I. Szentistvanyi
  • A. Rimanoczy
  • A. Juhasz
Original Investigations


The ionic regulating of lithium homeostasis and steady-state intra: extracellular lithium distribution in the brain can be approached by experimental methods using intact nerve cells in vitro. Primary cultures prepared from chick embryonic brain were applied to study the effect of extracellular sodium and potassium on the lithium uptake of nerve cells at ‘therapeutic’ lithium concentration (1.5 mM). Lithium influx and the level of steady-state intracellular lithium were significantly reduced by increasing the external sodium concentration. At physiological extracellular sodium level, the steady-state content of lithium in the brain cells was about half of that observed in the presence of 10 mM sodium in the incubation media and the value of the intra: extracellular lithium distribution ratio was below 1. External potassium (0.5–3 mM) strongly inhibited lithium uptake of the nerve cells. Ouabain (10-4M) had no effect on this potassiumsensitive lithium uptake in Tyrode media. Sodium influx studied by isotope tracer methodology was higher in cultures preloaded with lithium as compared to that of the controls. It can be concluded that sodium and potassium ions, at physiological concentrations, significantly influence lithium uptake as well as the intra: extracellular lithium distribution in brain cell cultures.

Key words

Lithium uptake Brain cell cultures Sodium and potassium effect Lithium homeostasis Lithium therapy 


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  1. Booher J, Sensenbrenner M (1972) Growth and cultivation of dissociated neurons and glial cells from embryonic chick, rat and human brain in flask cultures. Neurobiology 2:97–105Google Scholar
  2. Dorus E, Pandey GN, Shaughnessy R, Gaviria M, Val E, Ericksen S, Davis JM (1979) Lithium transport across red cell membrane: A cell membrane abnormality in manic-depressive illness. Science 205:932–934Google Scholar
  3. Duhm J, Becker BF (1979) Studies on lithium transport across the red cell membrane. V: On the nature of the Na+-dependent Li+ countertransport system of mammalian erythrocytes. J Membr Biol 51:263–286Google Scholar
  4. Duhm J, Eisenried F, Becker BF, Greil W (1976) Studies on the lithium transport across the red cell membrane. I. Li+ uphill transport by the Na+-dependent Li+ countertransport system of human erythrocytes. Plügers Arch 364:147–155Google Scholar
  5. Elizur A, Shopsin B, Gershon S, Ehlenberger A (1972) Intra: Extracellular lithium ratios and clinical course in affective states. Clin Pharmacol Ther 13:947–952Google Scholar
  6. Gorkin RA, Richelson E (1979) Lithium ion accumulation by cultured glioma cells. Brain Res 171:365–368Google Scholar
  7. Greil W, Eisenried F, Becker BF, Duhm J (1977) Interindividual differences in the Na+-dependent Li+ countertransport system and in the Li+ distribution ratio across the red cell membrane among Li+-treated patients. Psychophrmacology 53:19–26Google Scholar
  8. Haas M, Schooler J, Tosteson DC (1975) Coupling of lithium to sodium transport in human red cells. Nature 258:425–427Google Scholar
  9. Janka Z, Szentistvanyi I, Joo F, Juhasz A, Rimanoczy A (1979) Effects of lithium on morphological characteristics of dissociated brain cells in culture. Acta Neuropathol 46:117–121Google Scholar
  10. Janka Z, Szentistvanyi I, Juhasz A, Rimanoczy A (1980) Lithium transport difference between neuron and glia in primary culture. Neuropharmacology (in press)Google Scholar
  11. Kukes G, Elul G, DeVellis J (1976) The ionic basis of the membrane potential in a rat glial cell line. Brain Res 104:71–92Google Scholar
  12. Latzkovits L, Sensenbrenner M: Ion fluxes in cultures of dissociated brain cells. Abstracts of the IVth Intern Congr for Neurochem. Tokyo, p 119Google Scholar
  13. Latzkovits L, Sensenbrenner M, Mandel P (1974) Tracer kinetic model analysis of potassium uptake by dissociated nerve cell cultures: Glial-neuronal interrelationship. J Neurochem 23:193–200Google Scholar
  14. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ, (1951) Protein measurement with the Folin-phenol reagent. J Biol Chem 193:265–275Google Scholar
  15. Mendels J, Frazer A (1973) Intracellular lithium concentration and clinical response: Towards a membrane theory of depression. J Psychiatr Res 10:9–18Google Scholar
  16. Ostrow DG, Pandey GN, Davis JM, Hurt SW, Tosteson DC (1978) A heritable disorder of lithium transport in erythrocytes of a subpopulation of manic-depressive patients. Am J Psychiatry 135:1070–1078Google Scholar
  17. Pandey GN, Ostrow DG, Haas M, Dorus E, Casper RC, Davis JM, Tosteson DC (1977) Abnormal lithium and sodium transport in erythrocytes of a minic patient and some members of his family. Proc Natl Acad Sci USA 74:3607–3611Google Scholar
  18. Pandey GN, Sarkadi B, Haas M, Gunn RB, Davis JM, Tosteson DC (1978) Lithium transport pathways in human red blood cells. J Gen Physiol 72:233–247Google Scholar
  19. Ramsey TA, Frazer A, Mendels J, Dyson WL (1979) The erythrocyte lithium — plasma lithium ratio in patients with primary affective disorder. Arch Gen Psychiatry 36:457–461Google Scholar
  20. Richelson E (1977) Lithium ion entry through the sodium channel of cultured mouse neuroblastoma cells: A biochemical study. Science 196:1001–1002Google Scholar
  21. Richelson E, Gorkin RA (1979) Lithium ion entry into cultured cells of neural origin. In: Obiols J, Ballús C, Monclús EG, Pujol J (eds) Biological psychiatry today. Elsevier/North Holland, Amsterdam New York Oxford, p 1161Google Scholar
  22. Rybakowski J (1977) Pharmacogenetic aspect of red blood cell lithium index in manic-depressive psychosis. Biol. Psychiatry 12:425–429Google Scholar
  23. Sarkadi B, Alifimoff JK, Gunn RB, Tosteson DC (1978) Kinetics and stoichiometry of Na-dependent Li transport in human red blood cells. J Gen Physiol 72:249–256Google Scholar
  24. Schou M, Thomsen K (1975) Lithium prophylaxis of recurrent endogenous affective disorders. In: Johnson FN (ed) Lithium research and therapy. Academic Press, London New York San Francisco, p 63Google Scholar
  25. Szentistvanyi I, Janka Z (1979a) Correlation between the lithium ratio and Na-dependent Li transport of red blood cells during lithium prophylaxis. Biol Psychiatry 14:973–977Google Scholar
  26. Szentistvanyi I, Janka Z, Joo F, Juhasz A, Rimanoczy A (1978) Lithium transport and toxicity in brain cell cultures. In: Neuhoff V (ed) Verlag Chemie, Weinheim New York, p 500Google Scholar
  27. Szentistvanyi I, Janka Z, Joo F, Rimanoczy A, Juhasz A, Latzkovits L (1979b) Na-dependent Li-transport in primary nerve cell cultures. Neurosci Lett 13:157–161Google Scholar
  28. Szentistvanyi I, Janka Z, Rimanoczy A, Latzkovits L, Juhasz A (1979c) Comparison of lithium and sodium transports in primary cultures of dissociated brain cells. Cell Mol Biol 25:315–321Google Scholar
  29. Thomas RC, Simon W, Oehme M (1975) Lithium accumulation by snail neurones measured by a new Li+-sensitive microelectrode. Nature 258:754–756Google Scholar
  30. Wraae O, Hillman H, Round E (1976) The uptake of low concentrations of lithium ions into rat cerebral cortex slices and its dependence on cations. J Neurochem 26:835–843Google Scholar

Copyright information

© Springer-Verlag 1980

Authors and Affiliations

  • Z. Janka
    • 1
  • I. Szentistvanyi
    • 1
  • A. Rimanoczy
    • 1
  • A. Juhasz
    • 1
  1. 1.Department of Neurology and PsychiatryUniversity Medical SchoolSzegedHungary

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