Ca2+ regulation of connexin 43 hemichannels in C6 glioma and glial cells

De Vuyst, Elke, Wang, Nan, Decrock, Elke, De Bock, Marijke, Vinken, Mathieu, Van Moorhem, Marijke, Lai, Charles, Culot, Maxime, Rogiers, Vera, Cecchelli, Romeo, Naus, Christian C., Evans, William Howard and Leybaert, Luc 2009. Ca2+ regulation of connexin 43 hemichannels in C6 glioma and glial cells. Cell Calcium 46 (3) , pp. 176-187. 10.1016/j.ceca.2009.07.002

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Abstract

Connexin hemichannels have a low open probability under normal conditions but open in response to various stimuli, forming a release pathway for small paracrine messengers. We investigated hemichannel-mediated ATP responses triggered by changes of intracellular Ca2+ ([Ca2+]i) in Cx43 expressing glioma cells and primary glial cells. The involvement of hemichannels was confirmed with gja1 gene-silencing and exclusion of other release mechanisms. Hemichannel responses were triggered when [Ca2+]i was in the 500 nM range but the responses disappeared with larger [Ca2+]i transients. Ca2+-triggered responses induced by A23187 and glutamate activated a signaling cascade that involved calmodulin (CaM), CaM-dependent kinase II, p38 mitogen activated kinase, phospholipase A2, arachidonic acid (AA), lipoxygenases, cyclo-oxygenases, reactive oxygen species, nitric oxide and depolarization. Hemichannel responses were also triggered by activation of CaM with a Ca2+-like peptide or exogenous application of AA, and the cascade was furthermore operational in primary glial cells isolated from rat cortex. In addition, several positive feed-back loops contributed to amplify the responses. We conclude that an elevation of [Ca2+]i triggers hemichannel opening, not by a direct action of Ca2+ on hemichannels but via multiple intermediate signaling steps that are adjoined by distinct signaling mechanisms activated by high [Ca2+]i and acting to restrain cellular ATP loss.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
Uncontrolled Keywords:	calcium, glutamate, connexon, eicosanoids, gliotransmitter, glial cells
Publisher:	Elsevier
ISSN:	0143-4160
Last Modified:	17 Mar 2021 02:50
URI:	https://orca.cardiff.ac.uk/id/eprint/24245

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