Hypoxia-induced silencing of NMDA receptors in turtle neurons

被引:100
作者
Bickler, PE
Donohoe, PH
Buck, LT
机构
[1] Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA
关键词
anoxia; turtles; NMDA receptor; intracellular calcium; phosphatase; receptor downregulation;
D O I
10.1523/JNEUROSCI.20-10-03522.2000
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Hypoxia-induced suppression of NMDA receptors (NMDARs) in western painted turtle (Chrysemys picta) cortical neurons may be critical for surviving months of anoxic dormancy. We report that NMDARs are silenced by at least three different mechanisms operating at different times during anoxia. In pyramidal neurons from cerebrocortex, 1-8 min anoxia suppressed NMDAR activity (Ca2+ influx and open probability) by 50-60%. This rapid decrease in receptor activity was controlled by activation of phosphatase 1 or 2A but was not associated with an increase in [Ca2+](i). However, during 2 hr of anoxia, [Ca2+](i) in cerebrocortical neurons increased by 35%, and suppression of NMDARs was predicted by the increase of [Ca2+](i) and controlled by calmodulin. An additional mechanism of NMDAR silencing, reversible removal of receptors from the cell membrane, was found in cerebrocortex of turtles remaining anoxic at 3 degrees C for 3-21 d. When suppression of NMDARs was prevented with phosphatase inhibitors, tolerance of anoxia was lost. Silencing of NMDARs is thus critical to the remarkable ability of C. picta to tolerate life without oxygen.
引用
收藏
页码:3522 / 3528
页数:7
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