title: Protection against hypoxic-ischemic injury in transgenic mice overexpressing Kir6.2 channel pore in forebrain.
abstract: The role of the K-ATP channel pore-forming subunit Kir6.2 on protection from cerebral hypoxic-ischemic injury was assessed in transgenic mice overexpressing normal Kir6.2 or a dominant negative form (AFA) of this subunit in the forebrain. The resulting mice overexpress either the Kir6.2 or the AFA transgene mainly in the cerebral cortex and hippocampus. The Kir6.2 transgenic mice are resistant to hypoxic-ischemic injury showing a decreased region of cortical damage as compared to the dominant negative AFA and the wild-type mice. Moreover, the overexpression of Kir6.2 allowed an important silencing of the neurons present in forebrain regions thus protecting them from ischemic injury. Interestingly, the phenotype observed in Kir6.2 transgenic mice was observed without increased sulfonylurea binding. Taken together, these results indicate that the transgenic overexpression of Kir6.2 in forebrain significantly protects mice from hypoxic-ischemic injury and neuronal damage seen in stroke.
authors.affiliation: National Institutes of Health, Diabetes Branch, NIDDK, Bethesda, MD 20892-1758, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Héron-Milhavet
authors.forename: Yang
authors.initials: Y
authors.lastname: Xue-Jun
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Vannucci
authors.forename: Teresa L
authors.initials: TL
authors.lastname: Wood
authors.forename: Lisa B
authors.initials: LB
authors.lastname: Willing
authors.forename: Bethel
authors.initials: B
authors.lastname: Stannard
authors.forename: Catalina
authors.initials: C
authors.lastname: Hernandez-Sanchez
authors.forename: Charles
authors.initials: C
authors.lastname: Mobbs
authors.forename: Anne
authors.initials: A
authors.lastname: Virsolvy
authors.forename: Derek
authors.initials: D
authors.lastname: LeRoith
mesh_terms: D000200:Action Potentials / Q000235:genetics; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002544:Cerebral Infarction / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D020925:Hypoxia-Ischemia, Brain / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D007113:Immunity, Innate / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism; D010641:Phenotype; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism*; D016548:Prosencephalon / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013453:Sulfonylurea Compounds / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
chemical_list: D024661:Potassium Channels, Inwardly Rectifying; D013453:Sulfonylurea Compounds