The mammalian brain undergoes rapid cell death during
anoxia that is characterized by uncontrolled Ca(2+) entry via
N-methyl-D-aspartate receptors (NMDARs). In contrast, the western painted turtle is extremely
anoxia tolerant and maintains close-to-normal [Ca(2+)](i) during periods of
anoxia lasting from days to months. A plausible mechanism of anoxic survival in turtle neurons is the regulation of NMDARs to prevent excitotoxic Ca(2+) injury. However, studies using metabolic inhibitors such as
cyanide (NaCN) as a convenient method to induce
anoxia may not represent a true anoxic stress. This study was undertaken to determine whether turtle cortical neuron whole-cell NMDAR currents respond similarly to true
anoxia with N(2) and to NaCN-induced
anoxia. Whole-cell NMDAR currents were measured during a control N(2)-induced anoxic transition and a control NaCN-induced transition. During
anoxia with N(2) normalized, NMDAR currents decreased to 35.3%+/-10.8% of control values. Two different NMDAR current responses were observed during NaCN-induced
anoxia: one resulted in a 172%+/-51% increase in NMDAR currents, and the other was a decrease to 48%+/-14% of control. When responses were correlated to the two major neuronal subtypes under study, we found that stellate neurons responded to NaCN treatment with a decrease in NMDAR current, while pyramidal neurons exhibited both increases and decreases. Our results show that whole-cell NMDAR currents respond differently to NaCN-induced
anoxia than to the more physiologically relevant
anoxia with N(2).