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Pannexins in ischemia-induced neurodegeneration

Pannexin 1 (Px1, Panx1) and pannexin 2 (Px2, Panx2) form large-pore nonselective channels in the plasma membrane of cells and were suggested to play a role in the pathophysiology of cerebral ischemia. To directly test a potential contribution of pannexins in ischemia-related mechanisms, we performed...

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Main Authors: Bargiotas, Panagiotis (Author) , Krenz, Antje (Author) , Hormuzdi, Sheriar G. (Author) , Ridder, Dirk A. (Author) , Herb, Anne (Author) , Barakat, Waleed (Author) , Penuela, Silvia (Author) , Engelhardt, Jakob von (Author) , Monyer, Hannah (Author) , Schwaninger, Markus (Author)
Format: Article (Journal)
Language:English
Published: December 6, 2011
In: Proceedings of the National Academy of Sciences of the United States of America
Year: 2011, Volume: 108, Issue: 51, Pages: 20772-20777
ISSN:0027-8424
DOI:10.1073/pnas.1018262108
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1073/pnas.1018262108
Verlag, lizenzpflichtig, Volltext: https://www.pnas.org/content/108/51/20772
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Author Notes:Panagiotis Bargiotas, Antje Krenz, Sheriar G. Hormuzdi, Dirk A. Ridder, Anne Herb, Waleed Barakat, Silvia Penuela, Jakob von Engelhardt, Hannah Monyer, and Markus Schwaninger
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Summary:Pannexin 1 (Px1, Panx1) and pannexin 2 (Px2, Panx2) form large-pore nonselective channels in the plasma membrane of cells and were suggested to play a role in the pathophysiology of cerebral ischemia. To directly test a potential contribution of pannexins in ischemia-related mechanisms, we performed experiments in Px1−/−, Px2−/−, and Px1−/−Px2−/− knockout mice. IL-1β release, channel function in astrocytes, and cortical spreading depolarization were not altered in Px1−/−Px2−/− mice, indicating that, in contrast to previous concepts, these processes occur normally in the absence of pannexin channels. However, ischemia-induced dye release from cortical neurons was lower, indicating that channel function in Px1−/−Px2−/− neurons was impaired. Furthermore, Px1−/−Px2−/− mice had a better functional outcome and smaller infarcts than wild-type mice when subjected to ischemic stroke. In conclusion, our data demonstrate that Px1 and Px2 underlie channel function in neurons and contribute to ischemic brain damage.
Item Description:Gesehen am 17.02.2022
Physical Description:Online Resource
ISSN:0027-8424
DOI:10.1073/pnas.1018262108

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