ROS scavenging mimics anoxia by enhancing GABA receptor‐mediated electrical suppression in anoxia‐tolerant turtle cortex

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In anoxic mammalian brain, ATP dependent ion pumping is compromised and the consequent loss of membrane ion gradients elicits hyper‐excitability and cell death. This does not occur in the western painted turtle brain, where γ‐aminobutyric acid (GABA) concentration increases 80 fold and electrical activity decreases 75–95%. During anoxia, electrical suppression results from increased GABA receptor (GABAR)‐mediated postsynaptic currents (PSC) that shunt excitatory current, thereby avoiding excess AP firing. The signaling pathway responsible for initiating GABAergic neuroprotection is unknown but could involve decreases in the concentration of reactive oxygen species (ROS) that occurs following onset of anoxia. Using whole‐cell and perforated patch clamp techniques we determined that, similar to anoxia, ROS scavenging caused: whole cell conductance to increase from 4.5 ±0.4 to 6.6 ±1.1 nS; AP threshold to depolarize from 45 ± 4.2 to 24 ± 2.2 mV; and GABAR‐mediated currents to double in amplitude from 237.8 ± 81.6 to 449.8 ± 136.9 pA. Pharmacological anoxia (normoxic plus cyanide) caused a similar increase in GABAR current amplitude to 407.8 ± 38.5 pA and this was prevented by ROS donors (hydrogen peroxide or xanthine oxidase/xanthine). We conclude that a decrease in mitochondrial ROS production is the signal that increases GABAR currents during anoxic stress. Research supported by OGS scholarship to DWH, NSERC postdoctoral fellowship to MEP and an NSERC Discovery and Accelerator Grant to LTB.