title: Kir6.1 knockdown aggravates cerebral ischemia/reperfusion-induced neural injury in mice.
abstract: OBJECTIVE
  ATP-sensitive potassium (K-ATP) channels couple energy metabolism with electric activity, which play important roles in brain diseases including stroke. However, the impacts of Kir6.1-containing K-ATP channels that mainly expressed on glia in stroke remain unclear.
  
  
  RESULTS
  In this study, we found that expression of Kir6.1 was significantly decreased in the ischemic brain area of C57BL/6J mice after 1-h middle cerebral artery occlusion (MCAO) and 24-h reperfusion. Then, we subjected Kir6.1 heterozygote knockout (Kir6.1(+/-) ) mice to cerebral ischemia/reperfusion (I/R) injury and found that Kir6.1(+/-) mice exhibited exacerbated neurological disorder and enlarged infarct size, companied by glial over-activation and blood-brain barrier (BBB) damages. Furthermore, we showed that Kir6.1 knockdown aggravated endoplasmic reticulum (ER) stress and thereby increased the levels of proinflammatory factors tumor necrosis factor-α and interleukin-1β (TNF-α and IL-1β) in mouse brain.
  
  
  CONCLUSIONS
  Our findings reveal that Kir6.1 knockdown exacerbates cerebral I/R-induced brain damages via increasing ER stress and inflammatory response, indicating that Kir6.1-containing K-ATP channels may be a potential therapeutic target for stroke.
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Yin-Feng
authors.initials: YF
authors.lastname: Dong
authors.forename: Lin-Xiao
authors.initials: LX
authors.lastname: Wang
authors.forename: Xu
authors.initials: X
authors.lastname: Huang
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Cao
authors.forename: Ming
authors.initials: M
authors.lastname: Lu
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Ding
authors.forename: Xiu-Lan
authors.initials: XL
authors.lastname: Sun
authors.forename: Gang
authors.initials: G
authors.lastname: Hu
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D055785:Gene Knockdown Techniques / Q000379:methods; D054086:KATP Channels / Q000172:deficiency* / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D054086:KATP Channels; C092520:uK-ATP-1 potassium channel
keywords: ATP-sensitive potassium channel; ER stress; Inflammation; Kir6.1; Stroke