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Science 292 (5521): 1543-1546

Copyright © 2001 by the American Association for the Advancement of Science

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

Katsuya Yamada,1* Juan Juan Ji,1* Hongjie Yuan,1 Takashi Miki,4 Shinichi Sato,1 Naoki Horimoto,1 Tetsuo Shimizu,2 Susumu Seino,4 Nobuya Inagaki13dagger

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 KATP channels 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 KATP channels, 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.

1 Department of Physiology and
2 Department of Psychiatry, Akita University School of Medicine, and
3 CREST of Japan Science and Technology Cooperation (JST), 1-1-1, Hondo, Akita 010-8543, Japan.
4 Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-Ku, Chiba 260-8670, Japan.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed: E-mail: inagaki{at}med.akita-u.ac.jp

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