Effect of anoxia and pharmacological anoxia on whole-cell NMDA receptor currents in cortical neurons from the western painted turtle

The mammalian brain undergoes rapid cell death during anoxia that is characterized by uncontrolled Ca2+ entry via N-methyl-D- aspartate receptors (NMDARs). In contrast, the western painted turtle is extremely anoxia tolerant and maintains close-to-normal [Ca2+](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 Ca2+ 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 of 35.3% +/- 10.8% control values. Two different NMDAR current responses were observed during NaCN-induced anoxia: one resulted in a increase in NMDAR currents, and the other was 172% +/- 51% a decrease to of control. When responses were 48% +/- 14% 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.