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

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 hemichannelmediated 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.
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Cell Calcium, Elsevier, 2009, 46, p. 176-187
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Soumis le : mardi 7 décembre 2010 - 11:15:34
Dernière modification le : mardi 7 décembre 2010 - 11:15:34

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  • HAL Id : hal-00544068, version 1

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Elke De Vuyst, Nan Wang, Elke Decrock, Marijke De Bock, Mathieu Vinken, et al.. Ca2+ regulation of connexin 43 hemichannels in C6 glioma and glial cells. Cell Calcium, Elsevier, 2009, 46, p. 176-187. 〈hal-00544068〉

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