The inward rectifying potassium channel subtype Kir7.1 has been studied in a variety of potassium transporting epithelia in the retina, thyroid, intestine and kidney. The expression and function of Kir7.1 in the CNS is unresolved, although expression of these channels has been reported in cerebellar Purkinje neurons, hippocampal pyramidal neurons and neural stem cells. Here, we have assessed the expression and function of Kir7.1 in neurons and glia of the mouse CNS. Mice were euthanized humanely in accordance with the UK Animals Act (1986) and tissue was used for RT-PCR, Western blot, immunohistochemistry, tissue culture or isolated intact optic nerves for oxygen and glucose deprivation (OGD). Expression of Kir7.1 in adult brain and optic nerve was demonstrated by rtPCR and western blot. Immunolabelling with the Alomone aKir7.1 antibody confirmed previous reports of Kir7.1 expression in cerebellar Purkinje and hippocampal pyramidal neurons, and demonstrated immunolabelling in astrocytes and oligodendrocytes, the myelinating cells of the CNS. Glial and neuronal expression of Kir7.1 was confirmed in cultures of cells from the neonatal cortex and optic nerve. Like neurons, glial cells are susceptible to hypoxic/ischaemic injury, such as those that occur during stroke. A key factor in hypoxic/ischaemic episodes is that they cause depolarization of the resting membrane potential, resulting in cell dysfunction and death. Kir7.1 are highly sensitive to pH and are suppressed by extracellular acidification, such as occurs in ischemia. We therefore examined whether Kir7.1 may play a role in the susceptibility of glia to ischemia, in isolated intact optic nerves from mice aged postnatal day (P)10 mice subjected to oxygen and glucose deprivation (OGD). Incubation of optic nerves with the Kir7.1 channel blocker VU590 significantly increased cell death of optic nerve glia, measured using propidium iodide (PI) labelling (measured in a constant field of view (FOV), 6 FOV per nerve, n=4 nerves per group; 80 + 30 PI+ cells in controls and 189 + 49 PI+ cells in VU590; p<0.001, Anova). Our results demonstrate widespread expression of Kir7.1 in CNS neurons and glia, and indicate a functional importance in protecting glial cells from ischemic damage. Further studies are required to determine the biophysical properties of Kir7.1 and their pathophysiological function in neurons and glia.