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

    Research output: Contribution to journalArticle

    138 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

    Cite this

    Bargiotas, Panagiotis ; Krenz, Antje ; Hormuzdi, Sheriar G. ; Ridder, Dirk A. ; Herb, Anne ; Barakat, Waleed ; Penuela, Silvia ; von Engelhardt, Jakob ; Monyer, Hannah ; Schwaninger, Markus. / Pannexins in ischemia-induced neurodegeneration. In: Proceedings of the National Academy of Sciences of the United States of America. 2011 ; Vol. 108, No. 51. pp. 20772-20777.
    @article{a62408de96ef4458ba75bb61fe5a5a41,
    title = "Pannexins in ischemia-induced neurodegeneration",
    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.",
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    author = "Panagiotis Bargiotas and Antje Krenz and Hormuzdi, {Sheriar G.} and Ridder, {Dirk A.} and Anne Herb and Waleed Barakat and Silvia Penuela and {von Engelhardt}, Jakob and Hannah Monyer and Markus Schwaninger",
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    day = "20",
    doi = "10.1073/pnas.1018262108",
    language = "English",
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    Bargiotas, P, Krenz, A, Hormuzdi, SG, Ridder, DA, Herb, A, Barakat, W, Penuela, S, von Engelhardt, J, Monyer, H & Schwaninger, M 2011, 'Pannexins in ischemia-induced neurodegeneration', Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 51, pp. 20772-20777. https://doi.org/10.1073/pnas.1018262108

    Pannexins in ischemia-induced neurodegeneration. / Bargiotas, Panagiotis; Krenz, Antje; Hormuzdi, Sheriar G.; Ridder, Dirk A.; Herb, Anne; Barakat, Waleed; Penuela, Silvia; von Engelhardt, Jakob; Monyer, Hannah; Schwaninger, Markus.

    In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 51, 20.12.2011, p. 20772-20777.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Pannexins in ischemia-induced neurodegeneration

    AU - Bargiotas, Panagiotis

    AU - Krenz, Antje

    AU - Hormuzdi, Sheriar G.

    AU - Ridder, Dirk A.

    AU - Herb, Anne

    AU - Barakat, Waleed

    AU - Penuela, Silvia

    AU - von Engelhardt, Jakob

    AU - Monyer, Hannah

    AU - Schwaninger, Markus

    PY - 2011/12/20

    Y1 - 2011/12/20

    N2 - 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.

    AB - 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.

    KW - ATP release

    KW - gap junctions

    KW - macrophage

    KW - middle cerebral artery occlusion

    KW - metabolic inhibition

    KW - OXYGEN GLUCOSE DEPRIVATION

    KW - GAP-JUNCTION HEMICHANNELS

    KW - SPREADING DEPRESSION

    KW - CEREBRAL-ISCHEMIA

    KW - ATP RELEASE

    KW - INTERLEUKIN-1-BETA RELEASE

    KW - GLOBAL-ISCHEMIA

    KW - P2X(7) RECEPTOR

    KW - IN-VITRO

    KW - CHANNELS

    U2 - 10.1073/pnas.1018262108

    DO - 10.1073/pnas.1018262108

    M3 - Article

    C2 - 22147915

    VL - 108

    SP - 20772

    EP - 20777

    JO - Proceedings of the National Academy of Sciences

    JF - Proceedings of the National Academy of Sciences

    SN - 0027-8424

    IS - 51

    ER -