Journal
CNS NEUROSCIENCE & THERAPEUTICS
Volume 19, Issue 8, Pages 617-624Publisher
WILEY
DOI: 10.1111/cns.12117
Keywords
ATP-sensitive potassium channel; ER stress; Inflammation; Kir6.1; Stroke
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Funding
- National Natural Science Foundation of China [81030060, 81273495]
- National Key Basic Research Program of China [2009CB521906]
- National Science& Technology Major Project [2012ZX09304-001]
- Jiangsu Provincial Department of Education [12KJA310002]
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Background and PurposeATP-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. Methods and ResultsIn 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- and interleukin-1 (TNF- and IL-1) in mouse brain. ConclusionsOur 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.
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