Anoxia and NMDA Receptors
Brief periods of anoxia cause a marked, but apparently fully reversible interruption of integrated brain function, whose cellular mechanism is not yet fully understood. For some 50 years it has been known that the hippocampus is one of the first brain regions to be affected by anoxia (Sugar and Gerard 1937). This disruption results from at least two major changes: one is a marked enhancement of K+ conductance in pyramidal neurons, and a corresponding fall in excitability (Hansen et al. 1982; Misgeld and Frotscher 1984); another is sharp depression of Ca2+ currents (Krnjević and Leblond 1987; 1989). The latter may be of importance in explaining the block of synaptic transmission, as well as perhaps the early loss of cognitive function, in certain aspects of which hippocampal Ca2+ signals appears to play an essential role (eg. Teyler and DiScenna, 1987; Smith, 1987). A major component of the Ca2+ fluxes involved in long-term plastic changes follows activation of hippocampal NMDA receptors (Collingridge et al., 1983; McDermott et al., 1986); so it was of interest to see how anoxia and NMDA receptors might interact. This question could also be important in the light of much evidence that NMDA receptor-mediated Ca2+ influx is probably responsible for the selective necrosis of hippocampal pyramids (especially in CAl) induced by prolonged anoxia/ischemia (Choi, 1988; Siesjö and Bengtsson, 1989). This article briefly reviews some relevant experiments performed on hippocampal slices.
KeywordsNMDA Receptor Hippocampal Slice Depolarize Effect Cytoplasmic Calcium Concentration Reversible Interruption
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- Collingridge, G.L., Kehl, S.J., and McLennan, H., 1983, Excitatory amino-acids in synaptic transmission in the Schaffer collateral-commissural pathway of the rat hippocampus, J. Physiol., 334: 33.Google Scholar
- Krnjevi, K., Cherubini, E., and Ben-Ari, Y., 1989, Anoxia on slow inward currents of immature hippocampal neurons, J. Neurophysiol., 62, In press.Google Scholar
- Krnjevii, K., and Leblond, J., 1989, Changes in membrane currents of hippocampal neurons evoked by brief anoxia, J. Neurophysiol, 62: 15.Google Scholar
- Lobner, D., and Lipton, P., 1988, Glutamate receptors and irreversible anoxic damage in hippocampal slices: mechanisms of interaction, Soc. Neurosci. Abstr., 13: 647.Google Scholar
- MacDonald, J.F., Mody, I., and Salter, M.W., 1989, Regulation of N-methyl-D-aspartate receptors revealed by intracellular dialysis of murine neurones in culture, J. Physiol., 414: 17.Google Scholar
- Mcllwain, H., 1973, Consequences of cerebral hypoxia examined at tissue-metabolic level. In, Biochemistry of Cerebral Anoxia, Hypoxia an Ischemia, Ed. M.M. Cohen, Monogr. in Neural Sciences ( Karger, Basel ), 1: 122–129.Google Scholar
- Misgeld, U., and Frotscher, M., 1982, Dependence of the viability of neurons in hippocampal slices on oxygen supply, Brain Res. Bull., 8: 95.Google Scholar
- Siesjö B., and Bengtsson, F., 1989, Calcium fluxes, calcium antagonists, and calcium-related pathology in brain ischemia, hypoglycemia, and spreading depression: A unifying hypothesis, J. Cereb. Blood Flow Metabol., 9: 127.Google Scholar
- Smith, S.J., 1987, Progress on LTP at hippocampal synapses: a post-synaptic Ca2+ trigger for memory storage? TINS, 10: 142.Google Scholar
- Sugar, O., and Gerard, R.W., 1938, Anoxia and brain potentials, J. Neurophysiology, 1: 558.Google Scholar