Protective Role of ATP-Sensitive Potassium Channels in Hypoxia-Induced Generalized Seizure

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Abstract
Adenosine triphosphate (ATP)–sensitive potassium (KATP) channels are activated by various metabolic stresses, including hypoxia. The substantia nigra pars reticulata (SNr), the area with the highest expression of KATPchannels in the brain, plays a pivotal role in the control of seizures. Mutant mice lacking the Kir6.2 subunit of KATP channels [knockout (KO) mice] were susceptible to generalized seizures after brief hypoxia. In normal mice, SNr neuron activity was inactivated during hypoxia by the opening of the postsynaptic KATPchannels, whereas in KO mice, the activity of these neurons was enhanced. KATP channels exert a depressant effect on SNr neuronal activity during hypoxia and may be involved in the nigral protection mechanism against generalized seizures.