Protective role of ATP-sensitive potassium channels in hypoxia-induced generalized seizure.
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.
Yamada
K
K
Department of Physiology, Akita University School of Medicine, Hondo, Akita 010-8543, Japan.
Ji
J J
JJ
Yuan
H
H
Miki
T
T
Sato
S
S
Horimoto
N
N
Shimizu
T
T
Seino
S
S
Inagaki
N
N
D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D004569:Electroencephalography; D004576:Electromyography; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000235:genetics / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D012640:Seizures / Q000503:physiopathology* / Q000517:prevention & control; D013378:Substantia Nigra / Q000502:physiology* / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D005680:gamma-Aminobutyric Acid; D000255:Adenosine Triphosphate