Changes in Extracellular Ions Associated with Epileptiform Discharges

  • R. Pumain
  • U. Heinemann


Although it has been widely hypothesized that in the central nervous system of mammals the chemical composition of the extracellular fluid is maintained constant through precise regulatory mechanisms, it has become increasingly clear in the last 20 years that significant changes may occur during intense neuronal activity. In this respect, the development of ion-selective microelectrodes (Ammann, 1986) has been a decisive factor to determine the precise nature and extent of the possible ionic changes in the extracellular space. Indeed, it has long been known that nerve cell function is essentially underlain by transmembrane ionic currents, inwardly or outwardly directed, induced either through changes in membrane potential or the action of neurotransmitters. Therefore, any sustained activity of nerve cell could, in principle, alter the ion content of the extracellular or intracellular compartments. Thus, it has been shown that intense neuronal activity is associated with changes in the concentration of extracellular potassium ([K+]o), sodium ([Na+]o), calcium ([Ca2+]o), magnesium ([Mg2+]o), and chloride ([Cl−]o) ions and in pH (Benninger et al., 1980; ten Bruggencate et al., 1976; Dietzel et al., 1982; Futamachi et al., 1974; Heinemann and Lux, 1975; Kraig and Nicholson, 1978; Lux and Neher, 1973; Morris and Krnjevic, 1973; Nicholson et al., 1978; Prince et al., 1973; Pumain and Heinemann, 1985; Somjen, 1979, 1980; Sykova et al., 1976; Urbanics et al., 1978). The magnitude of the ion changes in the extracellular space depends not only on the transmembrane ionic fluxes but also on the volume of distribution of these ions and on how they migrate in the extracellular space.


Extracellular Space Hippocampal Slice Excitatory Amino Acid Epileptiform Activity Epileptiform Discharge 
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  1. Abbés, S., Louvel, J., and Pumain, R., 1988, Stimulus-induced extracellular calcium changes in in vitro somatosensory rat cortex, Eur. J. Neurosci. (Suppl. 68)16: 245.Google Scholar
  2. Ammann, D., 1986, Ion-selective micro electro des: Principles, design and application, Berlin, Heidelberg, New York, Tokyo, Springer-Verlag.Google Scholar
  3. Anderson, W.W., Lewis, D.V., Schwartzfelder, H.S., and Wilson, W.A., 1986, Magnesium-free medium activates seizure-like events in the rat hippocampal slice, Brain Res. 398: 215–219.Google Scholar
  4. Ascher, P. and Nowak, L., 1988, The role of divalent cations in the N-methyl-D-aspartate responses of mouse central neurones in culture, J. Physiol. (Lond.) 399: 247–266.Google Scholar
  5. Ascher, P., P. Bregestovski, P., and Nowak, L., 1988, N-methyl-D-aspartate activated channels of mouse central neurones in magnesium-free solutions, J. Physiol. (Lond.) 399: 207–226.Google Scholar
  6. Augustine, G.J., Charlton, M.P., and Smith, S.J., 1987, Calcium action in synaptic transmitter release, Ann. Rev. Neurosci. 10: 633–693.Google Scholar
  7. Avoli, M., Louvel, J., Pumain, R., and Olivier, A., 1987, Seizure-like discharges induced by lowering [Mg2+]o in the human epileptogenic neocortex maintained in vitro, Brain Res. 417: 199–203.Google Scholar
  8. Baker, P.F., and Reuter, H., 1975, Calcium movements in excitable cells, Oxford, New York, Toronto, Sydney, Braunschweig, Pergamon Press.Google Scholar
  9. Balestrino, M., Aitken, P.G., and Somjen, G.G., 1986, The effects of moderate changes of extracellular K+ and Ca2+ on synaptic and neural function in the CAl region of the hippocampal slice, Brain Res. 377: 229–239.Google Scholar
  10. Ballanyi, K., Grafe, P., and ten Bruggencate, G., 1987, Ion activities and potassium uptake mechanisms of glial cells in guinea-pig olfactory cortex slices, J. Physiol. (Lond.) 382: 159–174.Google Scholar
  11. Benninger, C., Kadis, J., and Prince, D.A., 1980, Extracellular calcium and potassium changes in hippocampal slices, Brain Res. 187: 165–182.Google Scholar
  12. Berdichevsky, E., Riveros, N., Sanchez-Armass, S., and Orrego, F., 1983, Kainate, N-methylaspartate and other excitatory amino acids increase calcium influx into rat brain cortex cells in vitro, Neurosci. Lett. 36: 75–80.Google Scholar
  13. Blaustein, M.P., 1974, The interrelationship between sodium and calcium fluxes across cell membranes, Rev. Physiol. Biochem. Pharmacol. 70: 33–82.Google Scholar
  14. Bondareff, W., and Pysh, J., 1968, Distribution of the extracellular space during postnatal maturation of rat cerebral cortex, Anat. Rec. 160: 773–780.Google Scholar
  15. Bossu, J.L., Feltz, A., and Thomann, J.M., 1985, Depolarization elicits two distinct calcium currents in vertebrate sensory neurones, Pflg. Arch. 403: 360–368.Google Scholar
  16. Bowman, C.L., and Kimeiberg, H.K., 1984, Excitatory amino acids directly depolarize rat brain astrocytes in primary culture, Nature 311: 656–659.Google Scholar
  17. Bowman, C.L., Kimeiberg, H.K., Frangakis, M.V., Berwald-Netter, Y., and Edwards, C., 1984, Astrocytes in primary culture have chemically activated sodium channels, J. Neurosci. 4: 1527–1534.Google Scholar
  18. Boyle, P.J., and Conway, E.J., 1941, Potassium accumulation in muscle and associated changes. J. Physiol. (Lond.) 100: 1–63.Google Scholar
  19. Bruggencate ten, G., Nicholson, C., and Stöckle, H., 1976, Climbing fiber evoked potassium release in cat cerebellum, Pflg. Arch. 367: 107–109.Google Scholar
  20. Bürhle, C., and Sonnhof, U., 1983, The ionic mechanism of the excitatory action of glutamate upon the membranes of motoneurones of the frog, Pflg. Arch. 396: 154–162.Google Scholar
  21. Carbone, E. and Lux, H.D., 1987, Single low-voltage-activated calcium channels in chick and rat sensory neurones. J. Physiol. (Lond.) 386: 571–601.Google Scholar
  22. Caspers, H., and Speckmann, E. J., 1969, DC potential shifts in paroxysmal states, in: Basic Mechanisms of the Epilepsies (H.H. Jasper, A.A. Ward, and A. Pope, eds.), Boston, Little Brown, pp. 375–388.Google Scholar
  23. Caspers, H. and Speckmann, E.J., 1972, Cerebral Po2, Pco2 and pH changes during convulsive activity and their significance for spontaneous arrest of seizures, Epilepsia 13: 699–725.Google Scholar
  24. Caspers, H., Speckmann, E.J., and Lehmenküller, A., 1987, DC potentials of the cerebral cortex. Seizure activity and changes in gas pressures, Rev. Physiol. Biochem. Pharmacol. 106: 127–178.Google Scholar
  25. Connor, E.A., Neel, D.S., and Parsons, R.L., 1985, Influence of the extracellular ionic environment on ganglionic fast excitatory postsynaptic currents, Brain Res. 339: 227–235.Google Scholar
  26. Connors, B.W., 1984, Initiation of synchronized neuronal bursting in neocortex, Nature 310: 685–687.Google Scholar
  27. Connors, B.W., and Ransom, B.R., 1984, Chloride conductance and extracellular potassium concentration interact to modify the excitability of rat optic nerve fibres, J. Physiol. (Lond.) 355: 619–633.Google Scholar
  28. Croucher, M.J., Collins, J.F., and Meldrum, B.S., 1982, Anticonvulsant action of excitatory amino-acid antagonists, Science 216: 899–901.Google Scholar
  29. Davies, J., Francis, A.A., Jones, A.W., and Wat-kins, J.C., 1981, 2-amino-5-phosphonovalerate (2APV), a potent and selective antagonist of amino-acid-induced and synaptic excitation, Neurosci. Lett. 77–81.Google Scholar
  30. Dietzel, I., and Heinemann, U., 1986, Dynamic variations of the brain cell microenvironment in relation to neuronal hyperactivity, Ann. NY Acad. Sci. 481: 72–86.Google Scholar
  31. Dietzel, L., Heinemann, U., Hofmeier, G., and Lux, H.D., 1980, Transient changes in the size of the extracellular space in the sensorimotor cortex of cats in relation to stimulus-induced changes in potassium concentration, Exp Brain Res. 40: 432–439.Google Scholar
  32. Dietzel, I., Heinemann, U., Hofmeier, G., and Lux, H.D., 1982, Stimulus induced changes in extracellular Na+ and Cl concentration in relation to changes in the size of the extracellular space, Exp. Brain Res. 46: 73–84.Google Scholar
  33. Dingledine, R., and Somjen, G.G., 1981, Calcium dependence and synaptic transmission in the hip-pocampal slice, Brain Res. 207: 218–222.Google Scholar
  34. Ebersole, J.S., and Chatt, A.B., 1980. The laminar susceptibility of cat visual cortex to penicillin-induced epileptogenesis, Neurology 30: 355.Google Scholar
  35. Eckert, R., and Chad, J.E., 1984, Inactivation of Ca2+ channels, Progr. Biophys. Molec. Biol. 44: 215–267.Google Scholar
  36. Erulkar, S.D., and Weight, F.F., 1977, Extracellular potassium and transmitter release at the giant synapse of squid, J. Physiol. (Lond.) 266: 209–218.Google Scholar
  37. Fertziger, A.P., and Ranck Jr., J.B., 1970, Potassium accumulation in interstitial space during epileptiform seizures, Exp. Neurol. 26: 571–585.Google Scholar
  38. Fisher, R.S., Pedley, T.A., Moody Jr., W.J., and Prince, D.A., 1976, The role of extracellular potassium in hippocampal epilepsy, Arch. Neurol. 33: 76–83.Google Scholar
  39. Fisher-Williams, M., Poncet, M., Riche, D., and Naquet, R., 1968, Light-induced epilepsy in the baboon Papio papio: Cortical and depth recordings, Electroencephalogr. Clin. Neurophy-siol. 25: 557–569.Google Scholar
  40. Fox, A.P., Nowycky, M.C., and Tsien, R.W., 1987, Single channel recordings of three types of cal-cium channels in chick sensory neurones. J. Physiol. (Lond.) 394: 173–200.Google Scholar
  41. Franceschetti, S., Hamon, B., and Heinemann, U., 1986, The action of valproate on spontaneous epileptiform activity in the absence of synaptic transmission and on evoked changes in [Ca2+]o in the hippocampal slice, Brain Res. 386: 1–11.Google Scholar
  42. Frankenhaeuser, B., and Hodgkin, A.L., 1957, The action of calcium on the electrical properties of squid axons, J. Physiol. (Lond.) 137: 218–244.Google Scholar
  43. Futamachi, K.J., and Pedley, T.A., 1976, Glial cells and extracellular potassium: Their relationship in mammalian cortex, Brain Res. 109: 311–322.Google Scholar
  44. Futamachi, K.J., Mutani, R., and Prince, D.A., 1974, Potassium activity in rabbit cortex, Brain Res. 75: 5–25.Google Scholar
  45. Gardner-Medwin, A.R., 1981, Possible roles of vertebrate neuroglia in potassium dynamics, spreading depression and migraine, J. Exp. Biol. 95: 111–127.Google Scholar
  46. Gardner-Medwin, A.R., 1983, Analysis of potassium dynamics in brain tissue, J. Physiol. (Lond.) 335: 393–426.Google Scholar
  47. Glötzner, F.L., 1973, Membrane properties of neuroglia in epileptogenic gliosis, Brain Res. 55: 159–171.Google Scholar
  48. Goddard, G.V., McIntyre, E.C., and Leech, C.K., 1969, A permanent change in brain function resulting from daily electrical stimulation, Exp. Neurol. 25: 295–330.Google Scholar
  49. Gumnit, R., Matsumoto, H., and Vasconetto, C., 1970, DC activity in the depth of an experimental focus, Electroencephalogr. Clin. Neurophysiol. 28: 333–339.Google Scholar
  50. Gutnick, M.J., and Prince, D.A., 1972, Thalamocortical relay neurons: antidromic invasion of spikes from a cortical epileptoghenic focus, Science 176: 406–437.Google Scholar
  51. Gutnick, M.J., Connors, B.W., and Ransom, B.R., 1981, Dye-coupling between glial cells in the guinea pig neocortical slice, Brain Res. 213: 486–492.Google Scholar
  52. Haas, H.L., and Jefferys, J.G.R., 1984, Low-calcium field burst discharges of CA1 pyramidal neurones in rat hippocampal slices, J. Physiol. (Lond.) 354: 185–201.Google Scholar
  53. Hablitz, J.J., and Heinemann, U., 1987, Extracellular K+ and Ca2+ changes during epileptiform discharges in the immature rat neocortex, Dev. Brain Res. 36: 299–303.Google Scholar
  54. Hablitz, J.J., and Lundervold, A., 1981, Hippocampal excitability and changes in extracellular potassium, Exp. Neurol. 71: 410–420.Google Scholar
  55. Hablitz, J.J., and Thalmann, R.H., 1987, Conductance changes underlying a late synaptic hyper-polarization in hippocampal CA3 neurons, J. Neurophysiol. 58: 160–179.Google Scholar
  56. Haglund, M.M., and Schwartzkroin, P.A., 1984, Seizure-like spreading depression in immature rabbit hippocampus in vitro, Brain Res. 316: 51–59.Google Scholar
  57. Hansen, A.J., and Olsen, C.E., 1980, Brain extracellular space during spreading depression and ischemia, Acta Physiol. Scand. 108: 355–365.Google Scholar
  58. Heinemann, U., and Dietzel, I., 1984, Extracellular potassium concentration in chronic alumina cream foci of cats, J. Neurophysiol. 52: 421–434.Google Scholar
  59. Heinemann, U., and Lux, H.D., 1975, Undershoots following stimulus induced rises of extracellular potassium concentration in cerebral cortex of cat, Brain Res. 93: 63–76.Google Scholar
  60. Heinemann, U., and Lux, H.D., 1977, Ceiling of stimulus induced rises in extracellular potassium concentration in the cerebral cortex of cats, Brain Res. 120: 231–249.Google Scholar
  61. Heinemann, U., Lux, H.D., and Gutnick, M.J., 1977, Extracellular free calcium and potassium during paroxysmal activity in cerebral cortex of the cats, Exp. Brain Res. 27: 237–243.Google Scholar
  62. Heinemann, U., Lux, H.D., Marciani, M.G., and Hofmeier, G., 1979, Slow potentials in relation to changes in extracellular potassium activity in the cortex of cats, in Origin of Cerebral Field Potentials (E.-J. Speckmann and H. Caspers, eds.), Stuttgart, Georg Thieme, pp. 33–48.Google Scholar
  63. Heinemann, U., and Pumain, R., 1980, Extracellular calcium activity changes in cat sensorimotor cortex induced by iontophoretic application of aminoacids, Exp. Brain Res. 40: 247–250.Google Scholar
  64. Heinemann, U., Franceschetti, S., Hamon, B., Konnerth, A., and Yaari, A., 1985, Effects of anticonvulsants on spontaneous epileptiform activity which develops in the absence of chemical synaptic transmission in hippocampal slices, Brain Res. 325: 349–352.Google Scholar
  65. Heinemann, U., Konnerth, A., Pumain, R., and Wadman, W.J., 1986, Extracellular calcium and potassium concentration changes in chronic epileptic brain tissue, in Advances in Neurology, vol. 44 (A.V. Delgado Escueta, A.A. Ward Jr, D.M. Woodbury, and R.J. Porter, eds.), New York, Raven Press, pp. 641–661.Google Scholar
  66. Helmquist, D., and Feldmann, D.S., 1966, Influence of ionic environment on acetylcholine release from motor nerve terminals. Acta Physiol. Scand. 67: 34–42.Google Scholar
  67. Herron, C.E., Williamson, R., and Collingridge, G.L., 1985, A selective N-methyl-D-aspartate an-tagonist depresses epileptiform activity in rat hip-pocampal slices, Neurosci. Lett. 61: 255–260.Google Scholar
  68. Hertz, L., 1986, Potassium transport in astrocytes and neurons in primary cultures, Ann. NY Acad. Sci. 481: 318–330.Google Scholar
  69. Hille, B., 1967, The selective inhibition of delayed potassium currents in nerve by tetraethylammo-nium ion, J. Gen. Physiol. 50: 287–302.Google Scholar
  70. Hille, B., 1984, Ionic channels of excitable membranes, Sunderland, MA, Sinauer Associates.Google Scholar
  71. Hirning, L.D., Fox, A.P., McCleskey, E.W., Olivera, B.M., Thayer, S.T., Miller, R.J., and Tsien, R.W., 1988, Dominant role of N-type Ca2+ channels in evoked release of norepinephrine from sympathetic neurons, Science 239: 57–61.Google Scholar
  72. Hounsgaard, J., and Nicholson, C., 1983, Potassium accumulation around individual Purkinje cells in cerebellar slices from the guinea-pig, J. Physiol. (Lond.) 340: 359–388.Google Scholar
  73. Jahnsen, H., and Llinas, R., 1984, Ionic basis for the electroresponsiveness and oscillatory properties of guinea-pig thalamic neurones in vitro. J. Physiol. (Lond.) 349: 227–247.Google Scholar
  74. Jefferys, J.G.R., 1981, Influence of electric fields on the excitability of granule cells in guinea-pig hip-pocampal slices, J. Physiol. (Lond.) 319: 143–152.Google Scholar
  75. Jefferys, J.G.R., and Haas, H.L., 1982, Synchronized bursting of CA1 hippocampal pyramidal cells in the absence of synaptic transmission, Nature 300: 448–450.Google Scholar
  76. Johnson, J.W., and Ascher, P., 1987, Glycine potentiates the NMDA response of mouse central neurones, Nature 325: 529–531.Google Scholar
  77. Johnston, D., and Brown, T.H., 1981, Giant synaptic potential hypothesis for epileptiform activity, Science 211: 294–297.Google Scholar
  78. Jones, R.S.G., and Heinemann, U., 1987, Pre and postsynaptic K+ and Ca2+ fluxes in area CA1 of the rat hippocampus in vitro: Effects of Ni2+, TEA and 4-AP, Exp. Brain Res. 68: 205–209.Google Scholar
  79. Katz, B., 1969, The release of neural transmitter substances, Liverpool, Liverpool University Press.Google Scholar
  80. Kettenmann, H., 1987, K+ and Cl uptake by cultured oligodendrocytes, Can. J. Physiol. Pharmacol. 65: 1033–1037.Google Scholar
  81. Kettenmann, H., and Ransom, B.R., 1988, Electrical coupling between oligodendrocytes studied in mammalian cell cultures, Glia 1: 64–73.Google Scholar
  82. Kettenmann, H., Sonnhof, U., and Schachner, M., 1983, Exclusive potassium dependence of the membrane potential in cultured mouse oligodendrocytes, J. Neurophysiol. 3: 500–505.Google Scholar
  83. Kimeiberg, H.K., 1981, Active accumulation and exchange transport of chloride in astroglial cells in culture, Biochem. Biophys. Acta 464: 179–184.Google Scholar
  84. Kocsis, J.D., and Waxman, S.G., 1980, Absence of potassium conductance in central myelinated axons, Nature 287: 348–349.Google Scholar
  85. Kocsis, J.D., Malenka, R.C., and Waxman, S.G., 1983, Effects of extracellular potassium concentration on the excitability of the parallel fibres of the rat cerebellum, J. Physiol. (Lond.) 334: 225–244.Google Scholar
  86. Konnerth, A., Heinemann, U., and Yaari, Y., 1986, Nonsynaptic epileptogenesis in the mammalian hippocampus in vitro. I. Development of seizure like activity in low extracellular calcium, J. Neurophysiol. 56: 409–423.Google Scholar
  87. Korn, J.S., Giacchino, J.L., Chamberlain, N.L., and Dingledine, R., 1987, Epileptiform burst activity induced by potassium in the hippocampus and its regulation by GABA-mediated inhibition, J. Neurophysiol. 57: 325–340.Google Scholar
  88. Kraig, R.P., and Nicholson, C., 1978, Extracellular ionic variations during spreading depression, Neuroscience 3: 1045–1059.Google Scholar
  89. Kraig, R.P., Ferreira-Filho, C.R., and Nicholson, C., 1983, Alkaline and acid transients in cerebellar microenvironment, J. Neurophysiol. 49: 831–850.Google Scholar
  90. Krnjevic, K., and Morris, M.E., 1972, Extracellular K+ activity and slow potential changes in spinal cord and medulla, Can. J. Physiol. Pharmacol. 50: 1214–1217.Google Scholar
  91. Krnjevic, K., and Schwartz, S., 1967, Some properties of unresponsive cells in the cerebral cortex, Exp. Brain Res. 3: 306–319.Google Scholar
  92. Krnjevic, K., Puil, E., and Werman, R., 1976, Intracellular Mg2+ increases neuronal excitability, Can. J. Physiol. Pharmacol. 54: 73–77.Google Scholar
  93. Krnjevic, K., Lamour, Y., Mac Donald, J.F., and Nistri, A., 1979, Effects of some divalent cations on motoneurones in cats, Can. J. Physiol. Pharmacol. 57: 944–956.Google Scholar
  94. Krnjevic, K., Morris, M.E., and Reiffenstein, R.F., 1982, Stimulation-evoked changes in extracellular K+ and Ca2+ in pyramidal layers of the rat’s hippocampus, Can. J. Physiol. Pharmacol. 60: 1643–1657.Google Scholar
  95. Lambert, J.D.C., Flatman, J.A., and Jahnsen, H., 1981, Extracellular recordings of amino acid induced potential changes in hippocampal slices, J. Neurosci. Meth. 3: 311–315.Google Scholar
  96. Lanter, F., Erno, D., Ammann, D., and W. Simon, 1980, Neutral carrier based ion-selective electrode for intracellular magnesium activity studies, Anal. Chem. 52: 2400–2402.Google Scholar
  97. Lehmenkühler, A., Zidek, W., and Caspers, H., 1982, Changes of extracellular Na+ and Cl activity in the brain cortex during seizure discharge, in Physiology and Pharmacology of Epileptic Phenomena (M.R. Klee, H.D. Lux, and E.-J. Speckmann, eds.), New York, Raven Press, pp. 37–45.Google Scholar
  98. Lehmenkühler, A., Caspers, H., and Kersting, U., 1985, Relations between DC potentials, extracellular ion activities, and extracellular volume fraction in the cerebral cortex with changes in Pco2, in Ion measurements in biology and Medecine (M. Kessler, D.K. Harrison, and J. Hoper, eds.), Berlin, Springer-Verlag, pp. 199–205.Google Scholar
  99. Lehmenkühler, A., Kersting, U., Richter, A., and Boerrigter, P., 1986, Relations of bioelectric activity, extracellular ion concentrations, and extracellular volume in cortical epileptic foci, in Epilepsy and Calcium (E.J. Speckmann, H. Schulze and J. Waiden, eds.), Munich, Urban and Schwarzenberg, pp. 227–246.Google Scholar
  100. Levin, V.A., Fenstermacher, J.D., and Patlak, C.S., 1970, Sucrose and inulin space measurements of cerebral cortex in four mammalian species, Am. J. Physiol 219: 1528–1533.Google Scholar
  101. Llinas, R., and Hess, R., 1976, Tetrodotoxin-resistant dendritic spikes in avian Purkinje cells, Proc. Natl. Acad. Sci. USA 73: 2520–2523.Google Scholar
  102. Llinas, R., and Jahnsen, H., 1982, Electrophysi-ology of mammalian thalamic neurones in vitro, Nature 297: 406–408.Google Scholar
  103. Lockton, J.W., and Holmes, O., 1980, Site of the initiation of penicillin-induced epilepsy in the cortex cerebri of the rat, Brain Res. 190: 301–304.Google Scholar
  104. Louvel, J., and Heinemann, U., 1980, Diminution de la concentration extracellulaire des ions calcium lors des crises épileptiques focales induites par l’oenanthotoxine dans le cortex du chat, CR Acad Sci. Paris 291: 997–1000.Google Scholar
  105. Louvel, J., Abbés, S., Godfraind, J.M., and Pumain, R., 1986, Effect of organic calcium channel blockers on neuronal calcium-dependent processes, in Calcium Electrogenesis and Neuronal Functioning (U. Heinemann, M. Klee, E. Neher and W. Singer, eds.), Springer-Verlag, Berlin, Heidelberg, New York, pp. 375–385.Google Scholar
  106. Louvel, J., Pumain, R., Roux, F.X., and Chodkiewicz, J.P., 1988, Excitatory amino acids effects in human neocortex: involvement of NMDA receptors in epilepsy, Eur. J. Neurosci. (Suppl. 84)7: 331.Google Scholar
  107. Lux, H.D., and Neher, E., 1973, The equilibration time course of [K+]o in cat cortex, Exp. Brain Res. 17: 190–205.Google Scholar
  108. Lux, H.D., Neher, E., and Marty, A., 1981, Single channel activity associated with the calcium dependent outward current in Helix pomatia, Pflg. Arch. 389: 293–295.Google Scholar
  109. Lux, H.D., Heinemann, U., and Dietzel, I., 1986, Ionic changes and alterations in the size of the extracellular space during epileptic activity, in Advances in Neurology Vol. 44 (A.V. Delgado Escueta, A.A. Ward Jr, D.M. Woodbury, and R.J. Porter, eds.), New York, Raven Press, 44: 619–639.Google Scholar
  110. MacDermott, A.B., Mayer, M.L., Westbrook, G.L., Smith, S.J., and Barker, J.L., 1986, NMDA-receptor activation increases cytoplasmic calcium concentration in cultured spinal cord neurones, Nature 321: 519–522.Google Scholar
  111. Mac Vicar, B.A., 1984, Voltage-dependent calcium channels in glial cells, Science 226: 1345–1347.Google Scholar
  112. Malenka, R.C., Kocsis, J.D., Ransom, B.R., and Wadxman, S.G., 1981, Modulation of parallel fiber excitability by postsynaptically mediated changes in extracellular potassium, Science 214: 339–341.Google Scholar
  113. Matsumoto, H., and Ajmone-Marsan, C., 1964, Cortical cellular phenomena in experimental epilepsy: interictal manifestations, Exp. Neurol. 9: 286–304.Google Scholar
  114. Mayer, M.L., 1985, A calcium-activated chloride current generates the after-depolarization of rat sensory neurones in culture, J. Physiol. (Lond.) 364: 217–239.Google Scholar
  115. Mayer, M.L., and Westbrook, G.L., 1987, The physiology of excitatory amino acids in the vertebrate central nervous system, Progr. Neurobiol. 28: 197–276.Google Scholar
  116. Mayer, M.L., Westbrook, G.L., and Guthrie, P.B., 1984, Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones. Nature 309: 261–263.Google Scholar
  117. McLaughlin, S.G.A., Szabo, G., and Eisenman, G., 1971, Divalent ions and the surface potential of charged phospholipid membranes, J. Gen. Physiol. 58: 667–668.Google Scholar
  118. Meech, R.W., 1978, Calcium-dependent potassium activation in nervous tissues, Ann. Rev. Biophys. Bioeng. 7: 1–18.Google Scholar
  119. Meldrum, B.S., Croucher, M.J., Czuczwar, S.J., Collins, J.F., Curry, K., Joseph, M., and Stone, T.W., 1983, A comparison of the anticonvulsant potency of (+ −)2-amino-5-phosphono valeric acid and (+−)2-amino-7-phosphonoheptanoic acid, Neuroscience 9: 925–930.Google Scholar
  120. Mody, I., and Heinemann, U., 1987, NMDA receptors of dentate gyrus granule cells participate in synaptic transmission following kindling, Nature 326: 701–704.Google Scholar
  121. Mody, I., Lambert, J.D.C., and Heinemann, U., 1987, Low extracellular magnesium induces epileptiform activity and spreading depressions in rat hippocampal slices, J. Neurophysiol. 57: 869–888.Google Scholar
  122. Mody, I., Stanton, P.K., and Heinemann, U., 1988, Activation of N-methyl-D-aspartate receptors parallels changes in cellular and synaptic properties of dentate granule cells after kindling, J. Neurophysiol 59: 1033–1054.Google Scholar
  123. Monaghan, D.T., and Cotman, C.W., 1985, Distribution of N-methyl-D-aspartate sensitive L-[3H] glutamate binding sites in rat brain, J. Neurosci. 5: 2909–2919.Google Scholar
  124. Moody, Jr., W.J., Futamachi, K.J., and Prince, D.A., 1974, Extracellular potassium activity during epileptogenesis, Exp. Neurol. 42: 248–263.Google Scholar
  125. Morris, M.E., and Krnjevic, K., 1973, Some measurements of extracellular potassium activity in the mammalian central nervous system, Adv. Exp. Med. Biol. 50: 129–143.Google Scholar
  126. Morris, M.E., and Krnjevic, K., 1981, Slow diffusion of Ca2+ in the rat’s hippocampus, Can. J. Physiol. Pharmacol. 59: 1022–1025.Google Scholar
  127. Naquet, R., Silva-Comte, C., and Menini, Ch., 1983, Implication of the frontal cortex in paroxysmal manifestations (EEG and EMG) induced by light stimulation in the Papio papio, in Epilepsy and motor system (E. Speckmann and C. Elger, eds.), Munich, Urban and Schwartzenberg, pp. 220–237.Google Scholar
  128. Newman, E.A., 1988, Potassium conductance in Müller cells of fish, Glia 1: 275–281.Google Scholar
  129. Nicholson, C., 1980, Dynamics of the brain cell microenvironment, Neurosci. Res. Prog. Bull. 18: 1–113.Google Scholar
  130. Nicholson, C., and Phillips, J.M., 1981, Ion diffusion modified by tortuosity and volume fraction in the extracellular microenvironment of the rat cerebellum, J. Physiol (Lond.) 321: 225–257.Google Scholar
  131. Nicholson, C., and Rice, M.E., 1986, The migration of substances in the neuronal microenvironment, Ann. NY Acad. Sci. 481: 55–66.Google Scholar
  132. Nicholson, C., and Rice, M.E., 1987, Calcium diffusion in the brain cell microenvironment, Can. J. Physiol Pharmacol. 65: 1086–1091.Google Scholar
  133. Nicholson, C., ten Bruggencate, G., Stöckle, H., and Steinberg, R., 1978, Calcium and potassium changes in extracellular microenvironment of cat cerebellar cortex, J. Neurophysiol. 41: 1026–1039.Google Scholar
  134. Nicholson, C., Phillips, J.M., and Gardner-Medwin, A.R., 1979, Diffusion from an ionto-phoretic point source in the brain: Role of tortuosity and volume fraction, Brain Res. 169: 580–584.Google Scholar
  135. Nowak, L., Bregestovski, P., Ascher, P., Herbet, A., and Prochiantz, A., 1984, Magnesium gates glutamate-activated channels in mouse central neurones, Nature 307: 462–465.Google Scholar
  136. Nowycky, M.C., Fox, A.P., and Tsien, R.W., 1984, Two components of calcium channel current in chick dorsal root ganglion cells, Biophys. J. 45, 36a.Google Scholar
  137. O’Leary, J.L., and Goldring, S., 1964, DC potentials of the brain, Physiol. Rev. 44: 91–125.Google Scholar
  138. Oliver, A.P., Hoffer, B.J., and Wyatt, R.W., 1978, Interaction of potassium and calcium in penicillin-induced interictal spike discharge in the hippocampal slice, Exp. Neurol. 62: 510–520.Google Scholar
  139. Orkand, R.K., 1980, Functional consequences of ionic changes resulting from electrical activity, Fed.Proc. 39: 1514–1543.Google Scholar
  140. Orkand, R.K., Nicholls, G.J., and Kuffler, S.W., 1966, Effect of nerve impulses on the membrane potential of glial cells in the central nervous system of amphibia, J. Neurophysiol. 29: 788–806.Google Scholar
  141. Parsons, R.L., Hofmann, W.W., and Feigen, J.J.A., 1965, Presynaptic effects of potassium ions on mammalian neuromuscular junction, Nature 208: 590–591.Google Scholar
  142. Pinault, D., and Pumain, R., 1985, Ectopic action potential generation: its occurrence in a chronic epileptogenic focus, Brain Res. 60: 599–602.Google Scholar
  143. Poolos, N.P., Mauk, M.D., and Kocsis, J.D., 1987, Activity-evoked increases in extracellular potassium modulate presynaptic excitability in the CA1 region of the hippocampus, J. Neurophysiol. 58: 404–416.Google Scholar
  144. Prince, D.A., 1968, The depolarization shift in “epileptic” neurons, Exp. Neurol. 21: 467–485.Google Scholar
  145. Prince, D.A., 1978, Neurophysiology of epilepsy, Ann. Rev. Neurosci. 1: 395–415.Google Scholar
  146. Prince, D.A., Lux, H.D., and Neher, E., 1973, Measurement of extracellular potassium activity in cat cortex, Brain Res. 50: 489–495.Google Scholar
  147. Pumain, R., 1981, Electrophysiological abnormalities in chronic epileptogenic foci: an intracellular study, Brain Res. 219: 445–450.Google Scholar
  148. Pumain, R., 1988, Calcium ions, in Neuromethods: The Neuronal Microenvironment (A.A. Boulton, B.A. Baker, and W. Walz, eds.), Clifton, NJ, The Humana Press, pp. 589–650.Google Scholar
  149. Pumain, R., and Heinemann, U., 1982, Intracellular potential and extracellular calcium changes in chronic epilepsy in Advances in Epileptology, XI-IIth Epilepsy International Symposium (H. Akimoto, H. Kazamatsuri, M. Seino and A. Ward, eds.), New York, Raven Press, pp. 497–500.Google Scholar
  150. Pumain, R., and Heinemann, U., 1985, Stimulus-and amino-acid induced calcium and potassium changes in rat neocortex, J. Neurophysiol. 53: 1–16.Google Scholar
  151. Pumain, R., Kurcewicz, I., and Louvel, J., 1983a, Fast extracellular calcium transients: Involvement in epileptic processes, Science 222: 177–179.Google Scholar
  152. Pumain, R., Kurcewicz, I., and Louvel, J., 1983b, Fast calcium and potassium transients recorded during single epileptic spikes in acute epilepsy, in Cerebral Blood Flow, Metabolism and Epilepsy (M. Baldy-Moulinier, D.-H. Ingvar, and B.S. Meldrum, eds.), London and Paris, John Libbey, Eurotext, pp. 278–284.Google Scholar
  153. Pumain, R., Menini, C., Heinemann, U., Louvel, J., and Silva Barrat, C., 1985, Chemical synaptic transmission is not necessary for epileptic seizures to persist in the baboon Papio papio, Exp. Neurol. 89: 250–258.Google Scholar
  154. Pumain, R., Louvel, J., and Kurcewicz, I., 1986, Long-term alterations in amino acid-induced ionic conductances in chronic epilepsy, in Excitatory Amino Acid and Epilepsy (R. Schwartz and Y. Ben Ari, eds.), New York, Plenum Press, York, pp. 439–447.Google Scholar
  155. Pumain, R., Kurcewicz, I., and Louvel, J., 1987a, Ionic changes induced by excitatory amino acids in the rat cerebral cortex, Can. J. Physiol. Pharmacol. 65: 1067–1077.Google Scholar
  156. Pumain, R., Louvel, J., and Kurcewicz, I., 1987b, Ionic mechanisms involved in the inactivation of paroxysmal discharges, in Inactivation of Hypersensitive Neurons (M. Chalazonitis, and M. Gola, eds.), New York, Alan R. Liss, York, pp. 9–16.Google Scholar
  157. Pumain, R., Kurcewicz, I., and Louvel, J., 1988, L-glutamate and its agonists: synaptic and ionic mechanisms in the central nervous system, in Neurotransmitters and Cortical Function. From Molecules to Brain (M. Avoli, T.A. Reader, R.W. Dykes, and P. Gloor, eds.), New York, Plenum Press, pp. 85–96.Google Scholar
  158. Ransom, B.R., Yamamate, C.L., and Connors, B.W., 1985, Activity dependent shrinkage of the extracellular space in rat optic nerve: A development study, J. Neurosci. 5: 532–535.Google Scholar
  159. Ransom, B.R., Carlini, W.G., and Connors, B.W., 1986, Brain extracellular space: Developmental studies in rat optic nerve, Ann. NY Acad. Sci. 481: 87–105.Google Scholar
  160. Schwartzkroin, P.A., Turner, D.A., and Wyler, A.R., 1983, Studies of human and monkey “epileptic” neocortex in the in vitro slice preparation, Ann. Neurol. 13: 249–257.Google Scholar
  161. Schwindt, P.C., Spain, W.J., Foehring, R.C., Stafstrom, C.E., Chubb, M.C., and Crill, W.E., 1988, Multiple potassium conductances and their functions in neurons from cat sensorimotor cortex in vitro, J. Neurophysiol. 59: 424–449.Google Scholar
  162. Skilling, S.R., Smullin, D., Beitz, A., and Larson, A.A., 1988, Extracellular amino acid concentrations in the dorsal spinal cord of freely moving rats following veratridine and nociceptive stimulation, J. Neurochem. 51: 127–132.Google Scholar
  163. Silinsky, E.M., 1985, The biophysical pharmacology of calcium-dependent acetylcholine secretion, Pharmacol. Rev. 37: 81–132.Google Scholar
  164. Somjen, G.G., 1975, Electrophysiology of neuroglia, Ann. Rev. Physiol. 37: 163–190.Google Scholar
  165. Somjen, G.G., 1979, Extracellular potassium in the mammalian central nervous system, Ann. Rev. Physiol. 41: 159–177.Google Scholar
  166. Somjen, G.G., 1980, Stimulus-evoked and seizure-related responses of extracellular calcium activity in spinal cord compared to those in cerebral cortex, J. Neurophysiol. 44: 617–632.Google Scholar
  167. Somjen, G.G., 1984, Interstitial ion concentration and the role of neuroglia in seizures, in Electro-physiology of Epilepsy (P.A. Schwartzkroin, and H. Wheal, eds.), London, Academic Press, pp. 302–341.Google Scholar
  168. Swandulla, D., and Lux, H.D., 1985, Activation of a nonspecific cation conductance by intracellular Ca2+ elevation in bursting pacemaker neurons of Helix pomatia, J. Neurophysiol. 54: 1430–1443.Google Scholar
  169. Sykova, E., 1987, Modulation of spinal cord transmission by changes in extracellular K+ activity and extracellular volume, Can. J. Physiol. Pharmacol. 65: 1058–1066.Google Scholar
  170. Sykova, E., Shirayev, B., Kriz, N., and Vyklicky, L., 1976, Accumulation of extracellular potassium in the spinal cord of frog, Brain Res. 106: 413–417.Google Scholar
  171. Tancredi, V., and Avoli, M., 1987, Control of spontaneous epileptiform discharges by extracellular potassium: An in vitro study in the CA1 subfield of the hippocampal slice, Exp. Brain Res. 67: 363–372.Google Scholar
  172. Taylor, C.P., and Dudek, F.E., 1982, Excitation of hippocampal pyramidal cells by an electrical field effect, J. Neurophysiol. 52: 126–142.Google Scholar
  173. Thomson, A.M., 1986, A magnesium-sensitive post-synaptic potential in rat cerebral cortex resembles neuronal responses to N-methylaspar-tate, J. Physiol. (Lond.) 370: 531–549.Google Scholar
  174. Thomson, A.M., West, D.C., and Lodge, D., 1985, A N-methylaspartate receptor-mediated synapse in rat cerebral cortex: A site of action of keta-mine? Nature 313: 479–481.Google Scholar
  175. Thompson, S.M., and Gähwiler, B.H., 1989, Activity-dependent disinhibition. II. Effects of extracellular potassium, furosemide, and membrane potential on ECl-in hippocampal CA3 neurons, J. Neurophysiol. 61: 512–523.Google Scholar
  176. Thompson, S.M., Diesz, R.A., and Prince, D.A., 1988, Outward chloride/cation co-transport in mammalian cortical neurones, Neurosci. Lett. 89: 49–54.Google Scholar
  177. Tsien, R.W., 1983, Calcium channels in excitable cell membranes, Ann. Rev. Physiol. 45: 341–358.Google Scholar
  178. Urbanics, R.E., Leninger-Follert, E., and Lübbers, D.W., 1978, Time course of changes of extracellular H+ and K+ during and after direct electrical stimulation of the brain cortex, Pflg. Arch. 378: 47–53.Google Scholar
  179. Van Harreveld, A., 1972, The extracellular space in the vertebrate central nervous system, in The Structure and Function of the Nervous Tissue, Vol. 4 (G.H. Bourne, ed.), New York, Academic Press, pp. 447–511.Google Scholar
  180. Van Harreveld, A., Crowell, J., and Malhotra, S.K., 1965, A study of extracellular space in central nervous tissue by freeze substitution, J. Cell Biol. 25: 117–137.Google Scholar
  181. Vyklicky, L., Sykova, E., and Kriz, N., 1975, Slow potential induced by changes of extracellular potassium concentration in the spinal cord of the cat, Brain Res. 87: 77–80.Google Scholar
  182. Walther, H., Lambert, J.D.C., Jones, R.S.G., Heinemann, U., and Hamon, B., 1986, Epileptiform activity in combined slices of the hippocampus, subiculum and entorhinal cortex during perfusion with low Mg2+ medium, Neurosci. Lett. 69: 156–161.Google Scholar
  183. Walz, W., 1987, Swelling and potassium uptake in cultured astrocytes, Can. J. Physiol. Pharmacol. 65: 1051–1057.Google Scholar
  184. Walz, W., and Hertz, L., 1983, Intracellular ion changes of astrocytes in response to extracellular potassium, J. Neurosci. Res. 10: 411–423.Google Scholar
  185. Watkins, J.C., and Evans, R.H., 1981, Excitatory amino acid transmitters, Ann. Rev. Pharmacol. Toxicol. 21: 165–204.Google Scholar
  186. Yim, C.C., Krnjevic, K., and Dalkara, T., 1986, Ephaptically generated potentials in CA1 neurons of rat’s hippocampus in situ, J. Neurophysiol. 56: 99–122.Google Scholar
  187. Yaari, Y., Konnerth, A., and Heinemann, U., 1983, Spontaneous epileptiform activity of CA1 hippocampal neurons in low extracellular calcium solutions, Exp. Brain Res 51: 153–156.Google Scholar
  188. Yaari, Y., Konnerth, A., and Heinemann, U., 1986, Non-synaptic epileptogenesis at the mammalian hippocampus in vitro. II. Role of extracellular potassium, J. Neurophysiol. 56: 424–438.Google Scholar
  189. Yamamoto, C., and Kawai, N., 1968, Generation of seizure discharge in thin sections from the guinea pig brain in chloride-free medium in vitro, Japn. J.Physiol. 18: 620–631.Google Scholar
  190. Zuckermann, E.C., and Glaser, G.H., 1968, Hippocampal epileptic activity induced by localized ventricular perfusion with high-potassium cerebrospinal fluid, Exp. Neurol. 20: 87–110.Google Scholar

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© Birkhäuser Boston, Inc. 1990

Authors and Affiliations

  • R. Pumain
  • U. Heinemann

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