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

Author:

Yamada Katsuya1,Ji Juan Juan1,Yuan Hongjie1,Miki Takashi2,Sato Shinichi1,Horimoto Naoki1,Shimizu Tetsuo3,Seino Susumu2,Inagaki Nobuya14

Affiliation:

1. Department of Physiology and

2. Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-Ku, Chiba 260-8670, Japan.

3. Department of Psychiatry, Akita University School of Medicine, and

4. CREST of Japan Science and Technology Cooperation (JST), 1-1-1, Hondo, Akita 010-8543, Japan.

Abstract

Adenosine triphosphate (ATP)–sensitive potassium (K ATP ) channels are activated by various metabolic stresses, including hypoxia. The substantia nigra pars reticulata (SNr), the area with the highest expression of K ATP channels in the brain, plays a pivotal role in the control of seizures. Mutant mice lacking the Kir6.2 subunit of K ATP 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 K ATP channels, whereas in KO mice, the activity of these neurons was enhanced. K ATP channels exert a depressant effect on SNr neuronal activity during hypoxia and may be involved in the nigral protection mechanism against generalized seizures.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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