Protective role ob ATP-sensitive potassium channels in hypoxia-induced generalized seizure

Adenosine triphosphate (ATP)-sensitive potassium (K-ATP) channels are activ ated by various metabolic stresses, including hypoxia. The substantia nigra pars reticulata (SNr), the area with the highest expression of K-ATP chann els in the brain, plays a pivotal role in the control of seizures. Mutant m ice lacking the Kir6.2 subunit of K-ATP channels [knockout (KO) mice] were susceptible to generalized seizures after brief hypoxia. In normal mice, SN r neuron activity was inactivated during hypoxia by the opening of the post synaptic K-ATP channels, whereas in KO mice, the activity of these neurons was enhanced. K-ATP channels exert a depressant effect on SNr neuronal acti vity during hypoxia and may be involved in the nigral protection mechanism against generalized seizures.