Pannexins in ischemia-induced neurodegeneration

Proc Natl Acad Sci U S A. 2011 Dec 20;108(51):20772-7. doi: 10.1073/pnas.1018262108. Epub 2011 Dec 6.

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-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / chemistry
  • Animals
  • Brain Ischemia / pathology
  • Connexins / genetics
  • Connexins / metabolism*
  • Gap Junctions
  • Gene Expression Regulation*
  • Infarction, Middle Cerebral Artery / pathology
  • Interleukin-1beta / metabolism
  • Ischemia / pathology*
  • Macrophages / metabolism
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurodegenerative Diseases / metabolism*
  • Neurons / metabolism

Substances

  • Connexins
  • Interleukin-1beta
  • Nerve Tissue Proteins
  • Panx1 protein, mouse
  • Panx2 protein, mouse
  • Adenosine Triphosphate