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Connexin and pannexin hemichannels in inflammatory responses of glia and neurons

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Autor dc.contributor.author Bennett M.V.L.
Autor dc.contributor.author Garre J.M.
Autor dc.contributor.author Orellana J.A.
Autor dc.contributor.author Bukauskas F.F.
Autor dc.contributor.author Nedergaard M.
Autor dc.contributor.author Saez J.C.
Fecha Ingreso dc.date.accessioned 2014-04-05T00:22:01Z
Fecha Disponible dc.date.available 2014-04-05T00:22:01Z
Fecha en Repositorio dc.date.issued 2014-04-04
dc.identifier 10.1016/j.brainres.2012.08.042
dc.description.abstract Mammals express ∼20 different connexins, the main gap junction forming proteins in mammals, and 3 pannexins, homologs of innexins, the main gap junction forming proteins in invertebrates. In both classes of gap junction, each channel is formed by two hemichannels, one contributed by each of the coupled cells. There is now general, if not universal, agreement that hemichannels of both classes can open in response to various physiological and pathological stimuli when they are not apposed to another hemichannels and face the external milieu. Connexin (and likely pannexin) hemichannel permeability is consistent with that of the cell-cell channels and open hemichannels can be a release site for relatively large molecules such as ATP and glutamate, which can serve as transmitters between cells. Here we describe three experimental paradigms in which connexin and pannexin hemichannel signaling occurs. (1) In cultures of spinal astrocytes FGF-1 causes the release of ATP, and ATP causes opening of pannexin hemichannels, which then release further ATP. Subsequently, several hours later, connexin hemichannels are also opened by an unknown mechanism. Release of ATP appears to become self sustaining through action of P2X7 receptors to open pannexin hemichannels and then connexin hemichannels, both of which are ATP permeable. (2) Spinal cord injury by dropping a small weight on the exposed cord is followed by release of ATP in the region surrounding the primary lesion. This release is greatly reduced in a mouse in which Cx43 is knocked down in the astrocytes. Application of FGF-1 causes a similar release of ATP in the uninjured spinal cord, and an inhibitor of the FGF-1 receptor, PD173074, inhibits both FGF-1 and injury-induced release. Reduction in ATP release is associated with reduced inflammation and less secondary expansion of the lesion. (3) Cortical astrocytes in culture are permeabilized by hypoxia, and this effect is increased by high or zero glucose. The mechanism of permeabilization is opening of Cx43 hemichannels, which can lead to cell death. Activated microglia secrete TNF-α and IL-1β, which open connexin hemichannels in astrocytes. Astrocytes release ATP and glutamate which can kill neurons in co-culture through activation of neuronal pannexin hemichannels. These studies implicate two kinds of gap junction hemichannel in inflammatory responses and cell death. This article is part of a Special Issue entitled Electrical Synapses. © 2012 Elsevier B.V. en_US
dc.source Brain Research
Link Descarga dc.source.uri http://www.scopus.com/inward/record.url?eid=2-s2.0-84869500645&partnerID=40&md5=6fc59a2ea553a5f7654aa18c7035e971
Title dc.title Connexin and pannexin hemichannels in inflammatory responses of glia and neurons en_US
Tipo dc.type Review
dc.description.keywords adenosine triphosphate; fibroblast growth factor 1; gap junction protein; glucose; glutamic acid; interleukin 1beta; pannexin; purinergic P2X7 receptor; tumor necrosis factor alpha; unclassified drug; astrocyte; cell culture; cell death; cell permeabilization; gene silencing; glia; immune response; in vitro study; microglia; nerve cell; nonhuman; priority journal; protein expression; review; signal transduction; spinal cord injury; Animals; Astrocytes; Connexin 43; Connexins; Fibroblast Growth Factor 1; Gap Junctions; Humans; Inflammation; Mice; Nerve Tissue Proteins; Neuroglia; Neurons; Spinal Cord Injuries; Invertebrata; Mammalia en_US


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