Bradley Heit and John Larson published a paper in the Journal of Physiology.
Mice lacking system xc- (xCT-/-), an astrocytic glutamate antiporter, exhibit 60-80% lower tonic extracellular glutamate concentrations than WT controls. In WT mice under anoxic challenge, tonic extracellular glutamate synergizes with excessive presynaptic (Pre) glutamate release, flooding the extracellular space, activating postsynaptic (Post) AMPA and NMDA receptors, and precipitating AD. Despite a greater abundance of postsynaptic AMPA receptors, these ischemia-driven events are significantly mitigated in xCT-/- mice due to the decrement of tonic glutamate. This ultimately reduces the accumulation of extracellular glutamate during anoxia, delays AD, and attenuates depolarizing AD waves in xCT-/- mice.
Heit, B.S., Chu, A., Sane, A., Featherstone, D.E., Park, T.J., & Larson, J. Tonic extracellular glutamate and ischemia: glutamate antiporter system xc- regulates anoxic depolarization in hippocampus. Journal of Physiology, 601 (2023) 607-629.