Regulation of Kv2.1 phosphorylation in an animal model of anoxia.
Conditions such as hypoxia and anoxia inflict serious damage to the brain and continue to be major medical problems. However, the molecular mechanisms that give rise to such damage are not well understood. To elucidate these mechanisms, we established a clinically relevant rodent model of anoxia/recovery by monitoring blood gas levels after oxygen deprivation. Using this animal model, we examined the regulation of Kv2.1, a voltage-gated potassium channel that plays pivotal roles in the homeostasis and survival of neurons. We found that exposure to anoxia induces rapid dephosphorylation of Kv2.1 in the brain, which can be blocked by pre-administration of a NMDA-type glutamate receptor antagonist, memantine. Furthermore, this change is rapidly reversed as the animal recovers from anoxic stress. These results suggest that Kv2.1 is tightly regulated in a clinically relevant animal model of anoxia and further implicate its role in the homeostasis of neurons during anoxic stress.
Ito
Takashi
T
Department of Pharmacology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
Nuriya
Mutsuo
M
Yasui
Masato
M
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D001923:Brain Chemistry / Q000235:genetics; D002470:Cell Survival / Q000502:physiology; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D002534:Hypoxia, Brain / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008559:Memantine / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism*; D010766:Phosphorylation; D051669:Shab Potassium Channels / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological / Q000502:physiology*; D013997:Time Factors
D018691:Excitatory Amino Acid Antagonists; C496990:Kcnb1 protein, mouse; D051669:Shab Potassium Channels; D008559:Memantine