Hypoxia-induced silencing of NMDA receptors in turtle neurons

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.