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

doi:10.1073/pnas.1018262108

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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191 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 language	English
Pages (from-to)	20772-20777
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	108
Issue number	51
DOIs	https://doi.org/10.1073/pnas.1018262108
Publication status	Published - 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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10.1073/pnas.1018262108

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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.",

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",

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",

year = "2011",

month = dec,

day = "20",

doi = "10.1073/pnas.1018262108",

language = "English",

volume = "108",

pages = "20772--20777",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

publisher = "National Academy of Sciences",

number = "51",

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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

SN - 0027-8424

VL - 108

SP - 20772

EP - 20777

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 51

ER -

Pannexins in ischemia-induced neurodegeneration

Abstract

Keywords

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