Reduction of NMDA receptor activity in cerebrocortex of turtles (Chrysemys picta) during 6 wk of anoxia.
Survival of brain anoxia during months of winter dormancy by the Western painted turtle, Chrysemys picta, may rely on inactivation of neuronal ion channels. During 2 h of anoxia, Ca2+ influx via the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor decreases 30-40%, but it is not known if prolonged anoxic dormancy is associated with even more profound downregulation of this important channel. Because ionized Ca2+ in cerebrospinal fluid (CSF) increases five- to sixfold during prolonged anoxia, the potential for uncontrolled Ca2+ influx and neurotoxicity is increased. To study the regulation of NMDA receptor activity, we measured NMDA-mediated changes in intracellular Ca2+ (NMDA-DeltaCa2+) in turtle cerebrocortical sheets with fura 2. Turtles were kept in N2-bubbled aquariums for 2 h to 6 wk at 2-3 degrees C. NMDA-DeltaCa2+ decreased 60 +/- 14% (P < 0.05) after 2 h of anoxia and did not decrease further for 6 wk. Intracellular Ca2+ increased from 135 to 183 nM (P < 0.05) after 3 wk of anoxia and thereafter returned toward preanoxic levels. When NMDA receptor activity was assessed in artificial CSF containing the ions found in anoxic brain CSF (pH 7. 25, 69 mM lactate, 8.4 mM Ca2+, and 5.1 mM Mg2+), NMDA-DeltaCa2+ was twice control initially but was 21% less than in normoxic artificial CSF after the end of 6 wk, suggesting altered sensitivity of the NMDA receptor to ionized Ca2+ during prolonged anoxia. Regulation of NMDA receptor activity in turtle cerebrocortex during 6 wk of anoxia thus results in depression of NMDA receptor Ca2+ flux, despite a sixfold increase in ionized extracellular Ca2+.
Bickler
P E
PE
Department of Anesthesia, University of California Medical Center, San Francisco, California 94143, USA.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D015536:Down-Regulation; D000860:Hypoxia / Q000503:physiopathology*; D009474:Neurons / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis*; D012016:Reference Values; D013997:Time Factors; D014426:Turtles
D016194:Receptors, N-Methyl-D-Aspartate; D002118:Calcium