Pflügers Archiv

, Volume 395, Issue 2, pp 108–114 | Cite as

Changes in extracellular potassium and calcium in rat cerebellar cortex related to local inhibition of the sodium pump

  • A. Ullrich
  • R. Steinberg
  • P. Baierl
  • G. ten Bruggencate
Excitable Tissues and Central Nervous Physiology


Extracellular K+, Ca2+, and Na+ ([K+]e, [Ca2+]e, [Na+]e) were recorded with ion selective microelectrodes in the cerebellar cortex of urethane-anesthetized rats. Superfusion of the cerebellum with artificial cerebrospinal fluid containing K-strophanthidin (10−6–10−4 mol/l) or other cardioactive steroids, known to be inhibitors of the sodium/potassium pump, had the following effects: elevation of resting [K+]3, reduction of poststimulus K+-undershoots, decrease of resting [Ca2+]e and [Na+]e. For instance, at 3×10−5 mol/l K-strophanthidin within the superfusion solution (the unknown intracerebellar concentration being certainly much smaller), [K+]e was elevated up to 130% and [Ca2+]e reduced to 70% of their resting values. Iontophoretic K+-pulses were enhanced in amplitude at the same time. Control experiments with iontophoretic TMA application demonstrated that the glycoside effects were not due (or in higher concentrations only partly due) to shrinkage of the extracellular fluid volume. When tetrodotoxin (10−7 mol/l) or Mn2+ (1–3 mmol/l) were additionally superfused, K-strophanthidin effects were qualitatively similar, though quantitatively smaller. This indicates that part of the effects were indirect via neuronal activity evoked by the blockade of the sodium pump. The experiments show that reduction of sodium pump activity in cerebellar cortex has rapid and serious consequences on the distribution of potassium and calcium in the extracellular space, resulting in an alteration of neuronal circuit excitability.

Key words

Sodium pump in CNS Extracellular potassium Cardiac glycosides Extracellular calcium K-Strophanthidin K+-Undershoot Inhibition of the sodium pump Cerebellar cortex 


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  1. Astrup J, Norberg K (1976) Potassium activity in cerebral cortex in rats during progressive severe hypoglycemia. Brain Res 103:418–423Google Scholar
  2. Baker PF, Blaustein MP, Keynes RD, Manie J, Shaw TI, Steinhardt RA (1969) The ouabain-sensitive fluxes of sodium and potassium in squid giant axon. J Physiol 200:459–496Google Scholar
  3. Blaustein MP (1974) The interrelationship between sodium and calcium fluxes across cell membranes. Rev Physiol Biochem Pharmacol 70:33–82Google Scholar
  4. Bruggencate G ten, Steinberg R (1978) Effects of ouabain and adenosine on extracellular Ca2+ an K+, as measured with ion selective microelectrodes in cerebellar cortex. Naunyn-Schmiedeberg's Arch Pharmacol 302:Suppl. 219Google Scholar
  5. Bureš J, Burešová O, Křivánek J (1974) The mechanism and applications of Leao's spreading depression of electroencephalographic activity. Academia, PragueGoogle Scholar
  6. Cohen LB, de Weer P (1977) Structural and metabolic processes directly related to action potential propagation. In: Kandel ER (ed) Cellular biology of neurons, part I (Handbook of physiology, section I, vol I, pp 137–159). Am Physiol Soc, Bethesda MDGoogle Scholar
  7. Cordingley GE, Somjen GG (1978) The clearing of excess potassium from extracellular space in spinal cord and cerebral cortex. Brain Res 151:291–306Google Scholar
  8. Dietzel J, Heinemann U, Hofmeier G, Lux HD (1980) Transient changes in the size of the extracellular space of the sensorimotor cortex of cats in relation to stimulus-induced changes in potassium concentration Exp Brain Res 40:432–439Google Scholar
  9. Engberg I, Källström Y, Marshall KC (1972) Double manipulator for independent impalement of one neurone with two electrodes. Acta Physiol Scand 84:4A-5AGoogle Scholar
  10. Erdman E, Schoner W (1973) Ouabain-receptor interactions in (Na++K+)-ATPase preparations. II. Effects of cations and nucleotides on rate constants and dissociation constants. Biochem Biophys Acta 330:302–315Google Scholar
  11. Erulkar SD, Weight FF (1977) Extracellular potassium and transmitter release at the giant synapse of squid. J Physiol 266:209–218Google Scholar
  12. Gillis RA, Quest JA (1980) The role of the nervous system in the cardiovascular effects of digitalis. Pharmacol Rev 31:19–97Google Scholar
  13. Hansen AJ (1977) Extracellular potassium concentration in juvenile and adult rat brain cortex during anoxia. Acta Physiol Scand 99:412–420Google Scholar
  14. Heinemann U, Lux HD (975) Undershoots following stimulus-induced rise of extracellular potassium concentration in cerebral cortex of cat. Brain Res 93:63–76Google Scholar
  15. Heinemann U, Lux HD, Zander KJ (1978) Effects of norepinephrine and DB-cAMP on active uptake of K+ in the cerebral cortex of cats. In: Ryall RW, Kelly JS (eds) Iontophoresis and transmitter mechanisms in the mammalian central nervous system, Elsevier, Amsterdam, pp 419–428Google Scholar
  16. Hertz L (1977) Drug-induced alterations of ion distribution at the cellular level of the central nervous system. Pharmacol Rev 29:36–65Google Scholar
  17. Krnjević K, Morris ME (1972) Extracellular K+-activity and slow potential changes in spinal cord and medulla. Can J Physiol Pharmacol 50:1214–1217Google Scholar
  18. Krnjević K, Morris ME (1975) Factors determining the decay of K+ potentials and focal potentials in the central nervous system. Can J Physiol Pharmacol 53:923–934Google Scholar
  19. Lendle L, Mercker H (1961) Extracardiale Digitaliswirkungen. Ergebn Physiol 51:199–298Google Scholar
  20. Llinás R (1979) The role of calcium in neuronal function In: Schmitt FO, Worden FG (eds) The neurosciences, 4th study programm. The MIT Press, Cambridge, MA, pp 555–571Google Scholar
  21. Lothman E, La Manna J, Cordingley GE, Rosenthal M, Somjen G (1975) Responses of electrical potential, potassium level and oxidative metabolic activity of the cerebral neocortex of cats. Brain Res 88:15–36Google Scholar
  22. Lux HD (1974) Fast recording ion specific electrodes. Their use in pharmacological studies in the CNS. Neuropharmacology 13:509–517Google Scholar
  23. Morris ME (1974) Hypoxia and extracellular potassium activity in the guinea pig cortex. Can J Physiol 52:872–882Google Scholar
  24. Narahashi I, Moore JW, Scott WR (1964) Tetrodotoxin blockade of sodium conductance increase in lobster giant axons. J Gen Physiol 47:965–974Google Scholar
  25. Nencini R, Pasquali E (1968) Manganese dioxide electrodes for stimulation and recording. Med Biol Engng 6:113–197Google Scholar
  26. Nicholson C (1979) Brain-cell microenvironment as a communication channel. In: Schmitt FO, Worden FG (eds) The neurosciences, 4th study program. The MIT Press, Cambridge, MA, pp 457–476Google Scholar
  27. Nicholson C, Phillips JM (1981) Ion diffusion modified by tortuosity and volume fraction in the extracellular microenvironment of the rat cerebellum. J Physiol 321:225–257Google Scholar
  28. Nicholson C, ten Bruggencate G, Steinberg R, Stöckle H (1977) Calcium modulation in brain extracellular microenvironment demonstrated with ion selective micropipette. Proc Natl Acad Sci [USA] 74: 1287–1290Google Scholar
  29. Nicholson C, ten Bruggencate G, Stöckle H, Steinberg R (1978) Calcium and potassium changes in extracellular microenvironment of cat cerebellar cortex. J Neurophysiol 41:1026–1039Google Scholar
  30. Osterberg RE, Rainer A (1973) Changes in spinal neural mechanisms associated with digitalis administration. J Pharmacol Exp Therap 187:246–259Google Scholar
  31. Pedley TA, Zuckermann EC, Glaser HG (1969) Epileptogenic effects of localized ventricular perfusion of ouabain on dorsal hippocampus. Exp Neurol 25:207–219Google Scholar
  32. Phillips JM, Nicholson C (1978) Tetra-alkyl ammonium ions as probes of brain cell microenvironment. Soc Neurosci Abstr 9:236Google Scholar
  33. Simon W, Amman D, Oehme M, Morf WE (1978) Calcium-selective electrodes. Ann NY Acad Sci 307:52–70Google Scholar
  34. Skou J (1965) Enzymatic basis for active transport of Na+ and K+ across cell membrane. Physiol Rev 45:586–617Google Scholar
  35. Steiner RA, Oehme M, Ammann D, Simon W (1979) Neutral carrrier Na+-selective microelectrode for intracellular studies. Anal Chem 51:351–353Google Scholar
  36. Ullrich A, Baierl P, ten Bruggencate G (1980) Extracellular potassium in rat cerebellar cortex during acute and chronic lithium application. Brain Res 192:287–290Google Scholar
  37. Vizi ES (1978) Na+-K+-activated adenosinetriphosphatase as a trigger in transmitter release. Neurosciences 3:367–384Google Scholar
  38. Vyklický L, Syková E (1980) The effects of increased extracellular potassium in the isolated spinal cord on the flexor reflex of the frog. Neurosci Lett 19:203–207Google Scholar
  39. Vyskočil R, Kříž N, Bureš J (1972) Potassium-selective microelectrodes used for measuring the extracellular brain potassium during spreading depression and anoxic depolarization in rats. Brain Res 39:255–259Google Scholar
  40. Yoda A, Hokin LE (1970) On the reversiblity of binding of cardiotonic steroids to a partially purified (Na+K)-activated adenosine-triphosphatase from beef brain. Biochem Biophys Res Commun 40: 880–886Google Scholar

Copyright information

© Springer-Verlag 1982

Authors and Affiliations

  • A. Ullrich
    • 1
  • R. Steinberg
    • 1
  • P. Baierl
    • 1
  • G. ten Bruggencate
    • 1
  1. 1.Department of PhysiologyUniversity of MünchenMünchen 2Germany

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