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The Effect of Hypoxia on Hippocampal Neurones and its Prevention by Ca2+-Antagonists

  • H. Higashi
  • S. Sugita
  • S. Nishi
  • K. Shimoji
Part of the Advances in Behavioral Biology book series (ABBI, volume 35)

Summary

The effects of hypoxia and high-potassium media on the rat hippocampal CA1 neurones in tissue slices were studied using intracellular electrodes. In response to superfusion with a hypoxic medium, a majority of the neurones showed a transient hyperpolarization followed by a slow depolarization at a plateau level of about 25 mV from the pre-hypoxic resting potential, and that evoked e.p.s.p.s were well preserved during hypoxic exposure. These results suggest that low oxygen tension per se may not be the major cause of neuronal dysfunction due to hypoxic hypoxia or ischaemia. In a minority of the neurones the slow depolarization was followed by a rapid depolarization, after which the neurones showed no functional recovery. Further analyses suggest that a marked influx of calcium ions probably triggers irreversible processes. In response to superfusion with potassium-rich (≥ 60 mM) media, all the neurones showed a marked depolarization of approximately 60 mV, and the membrane potential was irreversibly reduced to 0 mV even after washing out the media. The membrane dysfunction was blocked by removal of calcium or chloride ions, or addition of cobalt or organic calcium channel antagonists to the extracellular solution. In addition to these findings, the ionic mechanisms underlying the potential changes induced by hypoxia and the cause of the membrane dysfunction produced by potassium-rich media have been discussed.

Keywords

Input Resistance Hypoxic Exposure Sodium Pump Extracellular Potassium Concentration Membrane Dysfunction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Alger, B. E. & Nicoll, R. A., 1980, Spontaneous inhibitory postsynaptic potentials in hippocampus: mechanism for tonic inhibition, Brain Res., 200: 195–200.CrossRefGoogle Scholar
  2. Bingmann, D., Kolde, G. and Lipinski, H. G., 1984, Relation between P0z and neuronal activity in hippocampal slices, in: “Oxygen transport to tissue”, Vol. V, D. W. Lubbers, H. Acker, E. Leniger-Follert and T. K. Goldstick, eds., Plenum, New York, pp. 215–226.Google Scholar
  3. Brierly, J. B., 1976, Cerebral hypoxia, in: “Greenfield’s Neuropathology”, W. Blackwood and J. A. N. Corsellis, eds., Arnold, London, pp. 43–85.Google Scholar
  4. Brown, D. A. and Griffeth, W. H., 1983, Persistent slow inward calcium current in voltage-clamped hippocampal neurones of the guinea-pig, J. Physiol.(Lond.), 337: 303–320.Google Scholar
  5. Buckle, P. J. and Hass, H. L., 1982, Enhancement of synaptic transmission by 4-aminopyridine in hippocampal slices of the rat, J. Physiol. (Loud.), 326: 109–122.Google Scholar
  6. Cook, D. L. and Hales, N., 1984, Intracellular ATP directly blocks K+ channel in pancreatic B-cells, Nature (London), 311: 271–273.CrossRefGoogle Scholar
  7. Fujii, T., Baumgartle, H. and Lubbers, D. W., 1982, Limiting section thickness of guinea pig olfactory cortical slice studied from tissue p02 values and electrical activities, Pflügers Arch., 393: 83–87.CrossRefGoogle Scholar
  8. Fujiwara, N., Higashi, H., Shimoji, K. and Yoshimura, M. 1987, Effects of hypoxia on rat hippocampal neurones in vitro, J. Physiol. (Lond.), 384: 131–151.Google Scholar
  9. Hansen, A. J., 1977, Extracellular potassium concentration in juvenile and adult rat brain cortex during axion, Acta Physiol. Scand. 99: 412–420.Google Scholar
  10. Hansen, A. J., 1985, Effect of anoxia on ion distribution in the brain, Physiol. Rev., 65: 101–148.Google Scholar
  11. Hansen, A. J., Hounsgaard, J. and Jahnsen, H., 1982, Anoxia increases potassium conductance in hippocampal nerve cells, Acta Physiol. Scand., 115: 301–310.CrossRefGoogle Scholar
  12. Hass, W. K., 1981, Beyond cerebral blood flow, metabolism and ischemic thresholds: examination of the role of calcium in the initiation of cerebral infarction, in: “Cerebral Vascular Disease, Vol. 3, Proceedings of the 10th Salzburg Conference on Cerebral Vascular Disease”, J. S. Meyer, H. Lechner, M. Reivich, E. O. Ott and A. Arabinar, eds., Excerpta Medica, Amsterdam, pp. 3–17.Google Scholar
  13. Hossmann, K.-A., 1982, Treatment of experimental cerebral ischemia, J. Cereb. Blood Flow Metab., 2: 275–297.CrossRefGoogle Scholar
  14. Kakei, M. and Noma, A., 1984, Adenosine-5-triphosphate-sensitive single potassium channel in the atrioventricular node cell of the rabbit heart. J. Physiol. (Lond.), 352: 265–284.Google Scholar
  15. Kameyama, M., Kakei, M., Sato, R., Shibasaki, T., Matsuda, H. and Irisawa, H., 1984, Intracellular Na+ activates a K+ channel in mammalian cardiac cells, Nature (Lond.), 309: 354–356.CrossRefGoogle Scholar
  16. Kass, I. S. and Lipton, P., 1982, Mechanisms involved in irreversible anoxic damage to the in vitro rat hippocampal slice, J. Physiol. (Lond.), 332: 459–472.Google Scholar
  17. Kirino, T., 1982, Delayed neuronal death in the gerbil hippocampus following ischemia, Brain Res., 239: 57–69.CrossRefGoogle Scholar
  18. Meldrum, B., 1985, Excitatory animo acids and anoxic/ischaemic brain damage, Trends in Neurosci., 8: 47–48.CrossRefGoogle Scholar
  19. Newberry, N. R. and Nicoll, R. A., 1985, Comparison of the action of baclofen with y-amino-butyric acid on rat hippocampal pyramidal cells in vitro, J. Physiol. (Lond.), 360: 161–185.Google Scholar
  20. Noma, A., 1985, ATP-regulated single K channels in cardiac muscle, Nature (Lond.), 305: 147–148.CrossRefGoogle Scholar
  21. Reid, K., Schurr, A., Tseng, M. T. and Edmonds Jr., H. L., 1984, Resistance to hypoxia in the rat hippocampal slice, Brain Res. 302: 387–391.CrossRefGoogle Scholar
  22. Rothman, S. M., 1983, Synaptic activity mediates death of hypoxic neurons, Science, 220: 536–537.CrossRefGoogle Scholar
  23. Rothman, S. M., 1985, The neurotoxicity of excitatory amino acids is pro- duced by passive chloride influx, J. Neurosci., 5: 1483–1489.Google Scholar
  24. Scholfield, C. N., 1978, Electrical properties of neurones in the olfactory cortex slice in vitro, J. Physiol.(Lond.), 275: 535–546.Google Scholar
  25. Siesjö, B. K., 1981, Cell damage in the brain: a speculative synthesis, J. Cereb. Blood Flow Metab., 1: 155–185.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • H. Higashi
    • 1
    • 2
  • S. Sugita
    • 1
    • 2
  • S. Nishi
    • 1
    • 2
  • K. Shimoji
    • 1
    • 2
  1. 1.Department of PhysiologyKurume University School of MedicineKurume, 830Japan
  2. 2.Department of AnaesthesiologyNiigata University School of MedicineNiigata 951Japan

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