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Excitatory Amino Acids and Epilepsy-Induced Changes in Extracellular Space Size

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Excitatory Amino Acids and Epilepsy

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 203))

Summary

Convulsant and stimulus induced seizures are associated with Ca,Na, K and Cl concentration changes in the extracellular space (ES), which are a resultant of transmembrane ionic fluxes and of changes in the ES size. The ES decreases on average by 30% during a single seizure. An analysis of the causes of ES size changes reveal a large contribution from the spatial glia K buffer mechanism which may account for up to 60% of the ES decreases. NaC1 and KC1 uptake into cells as well as increases in intracellular osmolarity due to anaerobic glycolysis contribute less to the local cytotoxic edema but account for a net gain of osmotic active particle at the site of the focus. Excitatory amino acids such as glutamate, aspartate, N-methyl-D-aspartate (NMDA), kainate and quisqualate also lead to Na, Cl and eventually Ca uptake into cells and to release of K with dose dependent decreases in [Na]o, [Ca]o and [Cl]o, increases in [K]oand transient decreases in ES size by up to 80% which are possibly associated with a net reduction of osmotically active particles. The predominant cause for this cytotoxic edema is NaC1 uptake into cells but spatial K buffering through glial cells also contributes to this type of edema. The possible consequences of the various ion movements and the changes in osmolarity as well as ES size for tissue vulnerability are discussed.

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References

  • Bourke, R.S., and Nelson, L.R., 1972, Further studies on the K+-dependent swelling of primate cerebral cortex in vivo: the enzymatic basis of the K+-dependent transport of chloride, J. Neurochem., 19:663.

    Google Scholar 

  • Collins, R.C., and Olney, J.W., 1982, Focal cortical seizures cause distant thalamic lesions, Science, 218: 177.

    CAS  Google Scholar 

  • Connors, B.W., Ransom, B.R., Kunis, D.M., and Gutnick, M.J., 1982, Activity-dependent K+ accumulation in the developing rat optic nerve, Science, 216: 1341.

    Google Scholar 

  • Dietzel, I., Heinemann, U., Hofmeier, G., and Lux, H.D., 1980, Transient changes in the size of extracellular space in the sensorimotor cortex of cats in relation to stimulus-induced changes in potassium concentration, Exn. Brain Res., 40:432.

    Google Scholar 

  • 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.

    Google Scholar 

  • Dingledine, R., 1983, N-methyl aspartate activates voltage-dependent calcium conductance in rat hippocampal pyramidal cells, J. Phvsiol., 343:385.

    Google Scholar 

  • Engberg, I., Flatman, J.A., Lambert, J.D.C., and Lindsay, A., 1983, An analysis of bioelectrical phenomena evoked by microiontophoretically applied excitotoxic amino acids in the feline spinal cord, in: Excitotoxins, K. Fuxe, P.J. Roberts and R. Schwarcz, eds., Macmillan Press, London, p. 170.

    Google Scholar 

  • Evans, M.C., Griffiths, T., and Meldrum, B.S., 1984,. Kainic acid seizures and the reversibility of calcium loading in vulnerable neurones in the hippocampus, Neuropathol. Appl. Neurobiol., 10:285.

    Google Scholar 

  • Farber, J.L., 1981, The role of calcium in cell death, Life Sci., 29: 1289.

    CAS  Google Scholar 

  • Gardner-Medwin, A.R., 1983a, A study of the mechanisms by which potassium moves through brain-tissue in the rat, J. Physiol., 355:353.

    Google Scholar 

  • Gardner-Medwin, A.R., 1983b, Analysis of potassium dynamics in mammalian brain tissue, J. Physiol., 335:393.

    Google Scholar 

  • Griffiths, T., Evans, M.C., and Meldrum, B.S., 1982, Intracellular sites of early Ca2+ accumulation in the rat hippocampus during status epileptieus, Neurosci. Lett., 30:323.

    Google Scholar 

  • 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.

    CAS  Google Scholar 

  • Haas, H.L., and Jefferys, G.R., 1984, Low-calcium field burst discharges of CA1 pyramidal neurones in rat hippocampal slices, J. Phvsiol., 354:185.

    Google Scholar 

  • Harris, R.J., and Symon, I., 1984, Extracellular pH, potassium and calcium activities in progressive ischaemia of rat cortex, J. Cereb. Blood Flow Metab., 4:178.

    Google Scholar 

  • Heinemann, U., and Pumain, R., 1980, Extracellular calcium activity changes in cat sensorimotor cortex induced by iontophoretic application of amino acids, Exp. Brain Res., 40:247.

    Google Scholar 

  • Heinemann,U.,Neuhaus,S.,and Dietzel,I.,1983,Aspects of K regulation in normal and gliotic brain tissue,in: Cerebral Blood Flow, Metabolism and Epilepsy,M.Moulinier and B.S.Meldrum,eds.,John Libbez and Co.,London,p.271.

    Google Scholar 

  • Heinemann, U., and Dietzel, I., 1984, Extracellular potassium concentration in chronic alumina cream foci of cats, J. Neurophysiol.,52:421.

    Google Scholar 

  • Heinemann,U.,Konnerth,A.,Pumain,R.,and Wadman,W.,1986,Alterations of extracellular calcium sinks in chronic epileptic brain tissue, in: Basic Mechanisms of the Epilepsies: Cellular and Molecular Aspects, A.V.Delgado-Escueta,D.M.Woodbury, and K.Penry,eds.,Raven Press,New York,in press.

    Google Scholar 

  • Kimelberg,H.K.,and Ransom,B.R.,1986,Physiological aspects of astrocytic swelling,in: Astrocvtes, S.Federoff and A.Vernadakis,eds.,Academic Press,New York,in press.

    Google Scholar 

  • Konnerth, A., and Heinemann, U., 1983, Effects of GABA on presumed presynaptic Ca2+ entry in hippocampal slices, Brain Res., 270: 185.

    Google Scholar 

  • Kettenmann, H., Sonnhof, U., and Schachner, M., 1983, Exclusive K+ dependence of the membrane potential in cultured oligodendrocytes, J. Neurosci., 3:506

    Google Scholar 

  • Krnjevic, K., Morris, M.E., Reiffenstein, R.J., and Ropert, N., 1982, Depth distribution and mechanism of changes in extracellular K+ and Ca2+ concentrations in the hippocampus, Can J. Physiol. Pharmacol., 6:1958.

    Google Scholar 

  • Lambet,J.D.C.,and Heinemann,U.,1986,The involvement of Ca2+ and Mg` in responses of hippocampal CAS neurones to excitatory amino acids, in:Ca 2+ Electrogenesis and Neuronal Functioning, U. Heinemann,M.Klee,E.Neher,andW.Singer,eds.,Springer-Verlag,Heidelberg,Tokyo,New York,in press.

    Google Scholar 

  • Lassmann, H., Petsche, U., Kitz, K., Baran, H., Sperk, G., Seitelberger, F., and Hornykiewicz, 0., 1984, The role of brain edema in epileptic brain damage induced by systemic kainic acid injection, Neuroscience, 13: 691.

    CAS  Google Scholar 

  • Louvel,J.,1986,Effects of a calcium cha9nel blocker in ’normal’ and ’epileptic’ hippocampal slices,in:Ca4+ Electrogenesis and Neuronal Functioning,U.Heinemann,M.Klee,E.Neher,and W.Singer,eds.,Springer Verlag,Heidelberg,Tokyo,New York,in press.

    Google Scholar 

  • Lux, H.D., and Neher, E., 1973, The equilibrium time course of [K]0 in cat cortex, Exp. Brain Res., 17:190.

    Google Scholar 

  • Lux,H.D.,Heinemann,U.,and Dietzel,I.,1986,Ionic changes and changes in the size of the extracellular space in brain cortex during epileptic activity,in:Basic Mechanisms of the Epilepsies: Cellular and Molecular Aspects,A.V.Delgado-Escueta,D.M.Woodbury and K.Penry,eds.,Raven Press,New York,in press.

    Google Scholar 

  • Marciani, M.G., Louvel, J., and Heinemann, U., 1982, Aspartate induced changes in extracellular free calcium in vitro hippocampal slices of rats, Exp. Brain Res., 238:272.

    Google Scholar 

  • Meldrum, B.S., and Brierley, J.B., 1973, Prolonged epileptic seizures in primates: ischaemic cell change and its relation to ictal physiological events, Arch. Neurol., 28:10.

    Google Scholar 

  • 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., 321:225.

    Google Scholar 

  • Nowak, L., Bregestovski, P., Ascher, P., Herbet, A., and Prochiantz, A., 1984, Magnesium gates glutamate-activated channels in mouse central neurones, Nature, 307: 462.

    CAS  Google Scholar 

  • Orkand, R.K., Nicholls, J.G., 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.

    Google Scholar 

  • Orkand,R.K.,Cole,J.A., and Tsacopolous, M.,1986, The role of the glial cells in ion homeostasis in the retina of the honeybee drone, in: Calcium Electrogenesis and Neuronal Function, U.Heinemann, M.Klee,E.Neher and W.Singer,eds., Springer-Verlag,Heidelberg,Tokyo,New York,in press.

    Google Scholar 

  • Pumain, R., and Heinemann, U., 1985, Stimulus-evoked and amino acid induced ionic changes in rat neocortex, J. Neurophysiol., 53:1.

    Google Scholar 

  • Siesjö, B.K., 1981, Cell damage in the brain: a speculative synthesis, J. Cereb. Blood Flow Metab., 1:155.

    Google Scholar 

  • Somjen, G.G., 1980, Stimulus-evoked and seizure-related responses of extra-cellular calcium activity in spinal cord compared to those in cerebral cortex, J. Neurophysiol., 44:617.

    Google Scholar 

  • Somjen, G.G., 1983, Electrogenesis of sustained potentials, Prog. Neurobiol., 1:201.

    Google Scholar 

  • Sperk, G., Lassmann, H., Baran, H. Kish, S.J., Seitelberger, F., and Hornykiewicz, 0., 1983, Kainic acid induced seizures: neurochemical and histopathological changes, Neuroscience, 10: 1301.

    CAS  Google Scholar 

  • Walz, W., and Hertz, L., 1983, Functional interactions between neurons and astrocytes. H. Potassium homeostasis at the cellular level, Neurobiology, 20: 133.

    CAS  Google Scholar 

  • Watkins, J.C., 1984, Excitatory amino acids and central synaptic transmission, TIPS, 5: 373.

    Google Scholar 

  • Wong, R.K.S., and Traub, R.D., 1983, Synchronized burst discharge in disinhibited hippocampal slice. I. Initiation in CA2-CA3 region, J. Neurophvsiol „ 49:442.

    Google Scholar 

  • Yaari, Y., Konnerth, A., and Heinemann, U., 1986, Nonsynaptic epileptogenesis at the mammalian hippocampus in vitro. II. Role of extracellular potassium, J, Neurophvsiol., in press.

    Google Scholar 

  • Zanotto, L., and Heinemann, U., 1983, Aspartate and glutamate induced reductions in extracellular free calcium and sodium concentration in area CA1 of in vitro hippocampal slices of rats, Neurosci. Lett., 35:79.

    Google Scholar 

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© 1986 Plenum Press, New York

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Heinemann, U. (1986). Excitatory Amino Acids and Epilepsy-Induced Changes in Extracellular Space Size. In: Schwarcz, R., Ben-Ari, Y. (eds) Excitatory Amino Acids and Epilepsy. Advances in Experimental Medicine and Biology, vol 203. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-7971-3_34

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  • DOI: https://doi.org/10.1007/978-1-4684-7971-3_34

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-7973-7

  • Online ISBN: 978-1-4684-7971-3

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