Absence of a glutamatergic channel arrest mechanisms in hypoxic naked mole-rat cortex.

In the brain of hypoxia-intolerant vertebrates, hypoxia induces neuronal depolarization, chronic activation of voltage-gated excitatory glutamatergic receptors, and rapid accumulation of Ca2+ in the cytosol, which induces downstream activation of cell death pathways. Conversely, deleterious Ca2+ accumulation and cell death is avoided in the brain of hypoxia-tolerant vertebrates. One neuroprotective adaptation that is present in some of the most hypoxia-tolerant vertebrates is channel arrest, whereby Ca2+ ion influx through glutamate receptors is reduced in hypoxia, and cytotoxic accumulation of Ca2+ is avoided. Naked mole-rats are a hypoxia-tolerant mammal and avoid neurotoxic Ca2+ accumulation during hypoxia; however, the underlying mechanisms are poorly understood. In the present study, we tested the hypothesis that channel arrest of glutamatergic receptors occurs in hypoxic naked mole-rat neurons, which would help to limit Ca2+ influx during hypoxia. Using the Ca2+-sensitive fluorophore Fura-2, we measured Ca2+ flux through glutamatergic receptors in live brain slices exposed to a normoxic or hypoxic (1 % O2) perfusate and following application of either glutamate or NMDA to stimulate glutamatergic receptors. We found no differences in the magnitude of the evoked Ca2+ transients or the total amount of Ca2+ movement following ligand stimulus. Our results indicate that channel arrest is not an important strategy to limit deleterious Ca2+ influx into naked mole-rat neurons during hypoxia. Other mechanisms, such as enhanced mitochondrial buffering of cytosolic Ca2+, may play a more important role in hypoxic Ca2+ homeostasis in this species.