Cx43 Hemichannels and Gap Junction Channels in Astrocytes Are Regulated Oppositely by Proinflammatory Cytokines Released from Activated Microglia

• DOI: 10.1523/jneurosci.2042-07.2007
• Publication Date: 2007-12-12T17:28:38Z
• Authors: Mauricio A. Retamal; Nicolas Froger; Nicolas Palacios-...; Pascal Ezan; Pablo J. Sáez; Juan C. Sáez; Christian Giaume
• Keywords: Proinflammatory cytokine

Astrocytes have a role in maintaining normal neuronal functions, some of which depend on connexins, protein subunits gap junction channels and hemichannels. Under inflammatory conditions, microglia release cytokines, including interleukin-1β tumor necrosis factor-α, that reduce intercellular communication via junctions. Now, we demonstrate either conditioned medium harvested from activated or mixture these two cytokines enhances the cellular exchange with extracellular milieu Cx43 These changes membrane permeability were not detected astrocytes cultured knock-out mice abrogated by connexin hemichannel blockers, La 3+ , mimetic peptides, niflumic acid. Both reduction junctional increase mediated p38 mitogen-activated kinase-dependent pathway. However, permeability, but inhibition, was rapidly reversed sulfhydryl reducing agent dithiothreitol, indicating final regulatory mechanisms are different. Treatment proinflammatory reduced total cell surface levels, suggesting attributable to an hemichannels activity. Indeed, unitary events ∼220 pS corresponding much more frequent treated than under control conditions. Finally, effect enhanced uptake diffusion glucose, might explain metabolic status Accordingly, this opposite regulation may affect glucose trafficking certainly will modify involved brain inflammation.