Ca<SUP>2+</SUP> regulation of connexin 43 hemichannels in C6 glioma and glial cells - Archive ouverte HAL Access content directly
Journal Articles Cell Calcium Year : 2009

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

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Elke de Vuyst
  • Function : Author
Nan Wang
  • Function : Author
  • PersonId : 763528
  • IdRef : 169125947
Elke Decrock
  • Function : Author
Marijke de Bock
  • Function : Author
Mathieu Vinken
  • Function : Author
Marijke van Moorhem
  • Function : Author
Charles Lai
  • Function : Author
Vera Rogiers
  • Function : Author
Christian C. Naus
  • Function : Author
W. Howard Evans
  • Function : Author
Luc Leybaert
  • Function : Author

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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Dates and versions

hal-00544068 , version 1 (07-12-2010)

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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, 2009, 46, p. 176-187. ⟨hal-00544068⟩

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