Zions et al. show a dependence of captive naked mole-rats on elevated carbon dioxide (CO2) in the colony nest to avoid seizure. They also show a species-specific mutation of the neuronal potassium chloride cotransporter 2 (KCC2), compromising neuronal Cl- extrusion. Evolution may have favored selection of this energy-saving mutation, which is masked by the anticonvulsant properties of CO2.