Pannexins in ischemia-induced neurodegeneration

Panagiotis Bargiotas, Antje Krenz, Sheriar G. Hormuzdi, Dirk A. Ridder, Anne Herb, Waleed Barakat, Silvia Penuela, Jakob von Engelhardt, Hannah Monyer, Markus Schwaninger

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    159 Citations (Scopus)

    Abstract

    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-1 beta 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.

    Original languageEnglish
    Pages (from-to)20772-20777
    Number of pages6
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume108
    Issue number51
    DOIs
    Publication statusPublished - 20 Dec 2011

    Keywords

    • ATP release
    • gap junctions
    • macrophage
    • middle cerebral artery occlusion
    • metabolic inhibition
    • OXYGEN GLUCOSE DEPRIVATION
    • GAP-JUNCTION HEMICHANNELS
    • SPREADING DEPRESSION
    • CEREBRAL-ISCHEMIA
    • ATP RELEASE
    • INTERLEUKIN-1-BETA RELEASE
    • GLOBAL-ISCHEMIA
    • P2X(7) RECEPTOR
    • IN-VITRO
    • CHANNELS

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