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 Weste rn painted turtle, Chrysemys picta, may rely on inactivation of neuron al ion channels. During 2 h of anoxia, Ca2+ influx via the N-methyl-D- aspartate (NMDA) subtype of glutamate receptor decreases 30-40%, but i t is not known if prolonged anoxic dormancy is associated with even mo re profound downregulation of this important channel. Because ionized Ca2+ in cerebrospinal fluid (CSF) increases five-to sixfold during pro longed anoxia, the potential for uncontrolled Ca2+ influx and neurotox icity is increased. To study the regulation of NMDA receptor activity, we measured NMDA-mediated changes in intracellular Ca2+ (NMDA-Delta C a2+) in turtle cerebrocortical sheets with fura 2. Turtles were kept i n N-2-bubbled aquariums for 2 h to 6 wk at 2-3 degrees C. NMDA-Delta C a2+ decreased 60 +/- 14% (P < 0.05) after 2 h of anoxia and did not de crease further for 6 wk. Intracellular Ca2+ increased from 135 to 183 nM (P < 0.05) after 3 wk of anoxia and thereafter returned toward prea noxic levels. When NMDA receptor activity was assessed in artificial C SF containing the ions found in anoxic brain CSF (pH 7.25, 69 mM lacta te, 8.4 mM Ca2+, and 5.1 mM Mg2+), NMDA-Delta Ca2+ was twice control i nitially but was 21% less than in normoxic artificial CSF after the en d of 6 wk, suggesting altered sensitivity of the NMDA receptor to ioni zed Ca2+ during prolonged anoxia. Regulation of NMDA receptor activity in turtle cerebrocortex during 6 wk of anoxia thus results in depress ion of NMDA receptor Ca2+ flux, despite a sixfold increase in ionized extracellular Ca2+.