Appearance of NMDA receptors triggered by anoxia independent of voltage in vivo and in vitro.
Using rat hippocampus we have studied the pattern of neuronal death, abnormal discharge and loss of electrical excitability in slices prepared from animals subjected to bilateral, four-vessel cerebral anoxia and in slices prepared from normal animals that are subjected to anoxia in the recording chamber. As others have reported, pyramidal neurons in area CA1 are lost first after anoxia, while CA3 neurons have an intermediate sensitivity, and those in dentate are relatively anoxia-resistant. After anoxic damage to the intact animal, neurons in both CA1 and CA3 show abnormal bursting discharges in response to synaptic activation for several days, and then the response in CA1 decreases in amplitude and finally the area become unexcitable. While antagonists for N-methyl-D-aspartate (NMDA) receptors have essentially no effect on synaptic responses in control animals, they reduce the bursting responses and greatly depress the small responses in CA1 as neurons are becoming unexcitable after anoxia. With intracellular recording CA1 neurons from animals made transiently anoxic, in contrast to controls, show prolonged synaptic responses, the later components of which are blocked by NMDA antagonists. When slices from normal animals are subjected to anoxia such that excitability is totally lost over a period of about 10 min, there is no significant membrane depolarization during the anoxic episode and recovery of excitability occurs with reoxygenation. However, a period of hyperexcitability and bursting follows and electrical excitability is lost in CA1 but not CA3 neurons after about 90 min.(ABSTRACT TRUNCATED AT 250 WORDS)
Hori
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N
Wadsworth Center for Laboratories and Research, New York State Department of Health, Albany 12201-0509.
Doi
N
N
Miyahara
S
S
Shinoda
Y
Y
Carpenter
D O
DO
D000818:Animals; D002470:Cell Survival; D004594:Electrophysiology; D002534:Hypoxia, Brain / Q000378:metabolism*; D066298:In Vitro Techniques; D009474:Neurons / Q000502:physiology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*
D016194:Receptors, N-Methyl-D-Aspartate