title: Role of Hemichannels in CNS Inflammation and the Inflammasome Pathway.
abstract: Neurodegenerative, cardiovascular, and metabolic disorders, once triggered, share a number of common features, including sustained inflammatory cell activation and vascular disruption. These shared pathways are induced independently of any genetic predisposition to the disease or the precise external stimulus. Glial cells respond to injury with an innate immune response that includes release of proinflammatory cytokines and chemokines. Vascular endothelial cells may also be affected, leading to opening of the blood-brain barrier that facilitates invasion by circulating inflammatory cells. Inflammation can trigger acute neural injury followed by chronic inflammation that plays a key role in neurodegenerative conditions. Gap junction channels normally allow direct cell-to-cell communication. They are formed by the docking of two hemichannels, one contributed by each of the neighboring cells. While the opening probability of these channels is tightly controlled under resting conditions, hemichannels can open in response to injury or inflammatory factors, forming a large, relatively nonselective membrane pore. In this review, we consider the CNS immune system from the perspective that modulating connexin hemichannel opening can prevent tissue damage arising from excessive and uncontrolled inflammation. We discuss connexin channel roles in microglia, astrocytes, and endothelial cells in both acute and chronic inflammatory conditions, and in particular describe the role of connexin hemichannels in the inflammasome pathway where they contribute to both its activation and its spread to neighboring cells. Finally, we describe the benefits of hemichannel block in animal models of brain injury.
authors.affiliation: Department of Ophthalmology and New Zealand National Eye Centre, Auckland, New Zealand.
authors.forename: Yeri
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Physiology, Faculty of Medical and Health Sciences, Auckland, New Zealand.
authors.forename: Joanne O
authors.initials: JO
authors.lastname: Davidson
authors.affiliation: Department of Physiology, Faculty of Medical and Health Sciences, Auckland, New Zealand.
authors.forename: Katherine C
authors.initials: KC
authors.lastname: Gunn
authors.affiliation: School of Biological Sciences, University of Auckland, Auckland, New Zealand.
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Phillips
authors.affiliation: Department of Ophthalmology and New Zealand National Eye Centre, Auckland, New Zealand.
authors.forename: Colin R
authors.initials: CR
authors.lastname: Green
authors.affiliation: Department of Physiology, Faculty of Medical and Health Sciences, Auckland, New Zealand. Electronic address: aj.gunn@auckland.ac.nz.
authors.forename: Alistair J
authors.initials: AJ
authors.lastname: Gunn
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D002493:Central Nervous System Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D017630:Connexins / Q000378:metabolism* / Q000627:therapeutic use; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D017628:Microglia / Q000378:metabolism / Q000473:pathology
chemical_list: D017630:Connexins; D058847:Inflammasomes
keywords: Blood–brain barrier; Cerebral ischemia; Connexin 43; Connexin hemichannels