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-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.
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology,  University of Lübeck, 23538 Lubeck,  Germany.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Bargiotas
authors.forename: Antje
authors.initials: A
authors.lastname: Krenz
authors.forename: Sheriar G
authors.initials: SG
authors.lastname: Hormuzdi
authors.forename: Dirk A
authors.initials: DA
authors.lastname: Ridder
authors.forename: Anne
authors.initials: A
authors.lastname: Herb
authors.forename: Waleed
authors.initials: W
authors.lastname: Barakat
authors.forename: Silvia
authors.initials: S
authors.lastname: Penuela
authors.forename: Jakob
authors.initials: J
authors.lastname: von Engelhardt
authors.forename: Hannah
authors.initials: H
authors.lastname: Monyer
authors.forename: Markus
authors.initials: M
authors.lastname: Schwaninger
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D000818:Animals; D002545:Brain Ischemia / Q000473:pathology; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D017629:Gap Junctions; D005786:Gene Expression Regulation; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D053583:Interleukin-1beta / Q000378:metabolism; D007511:Ischemia / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism
chemical_list: D017630:Connexins; D053583:Interleukin-1beta; D009419:Nerve Tissue Proteins; C503631:Panx1 protein, mouse; C516139:Panx2 protein, mouse; D000255:Adenosine Triphosphate