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Permeation of molecules through astroglial connexin 43 hemichannels is modulated by cytokines with parameters depending on the permeant species

dc.contributor.authorSáez J.C.
dc.contributor.authorVargas A.A.
dc.contributor.authorHernández D.E.
dc.contributor.authorOrtiz F.C.
dc.contributor.authorGiaume C.
dc.contributor.authorOrellana J.A.
dc.date.accessioned2020-09-02T22:28:49Z
dc.date.available2020-09-02T22:28:49Z
dc.date.issued2020
dc.identifier10.3390/ijms21113970
dc.identifier.citation21, 11, -
dc.identifier.issn16616596
dc.identifier.urihttps://hdl.handle.net/20.500.12728/6358
dc.descriptionRecent studies indicate that connexin hemichannels do not act as freely permeable non-selective pores, but they select permeants in an isoform-specific manner with cooperative, competitive and saturable kinetics. The aim of this study was to investigate whether the treatment with a mixture of IL-1β plus TNF-α, a well-known pro-inflammatory condition that activates astroglial connexin 43 (Cx43) hemichannels, could alter their permeability to molecules. We found that IL-1β plus TNF-α left-shifted the dye uptake rate vs. dye concentration relationship for Etd and 2-NBDG, but the opposite took place for DAPI or YO-PRO-1, whereas no alterations were observed for Prd. The latter modifications were accompanied of changes in Kd (Etd, DAPI, YO-PRO-1 or 2-NBDG) and Hill coefficients (Etd and YO-PRO-1), but not in alterations of Vmax. We speculate that IL-1β plus TNF-α may distinctively affect the binding sites to permeants in astroglial Cx43 hemichannels rather than their number in the cell surface. Alternatively, IL-1β plus TNF-α could induce the production of endogenous permeants that may favor or compete for in the pore-lining residues of Cx43 hemichannels. Future studies shall elucidate whether the differential ionic/molecule permeation of Cx43 hemichannels in astrocytes could impact their communication with neurons in the normal and inflamed nervous system. © 2020 by the authors.
dc.language.isoen
dc.publisherMDPI AG
dc.subjectAstrocytes
dc.subjectConnexons
dc.subjectDyes
dc.subjectIL-1β
dc.subjectPermeability tracers
dc.subjectPermeation
dc.subjectTNF-α
dc.subjectcalcium ion
dc.subjectconnexin 43
dc.subjectcytochrome b
dc.subjectcytokine
dc.subjectdivalent cation
dc.subjectglucose transporter 1
dc.subjectinterleukin 1beta
dc.subjectmagnesium ion
dc.subjectnucleic acid
dc.subjecttumor necrosis factor
dc.subjectanimal experiment
dc.subjectArticle
dc.subjectastrocyte
dc.subjectbinding site
dc.subjectcell proliferation
dc.subjectconfocal microscopy
dc.subjectcontrolled study
dc.subjectfluorescence imaging
dc.subjectfluorescence microscopy
dc.subjectgenetic transfection
dc.subjectIC50
dc.subjectimmunofluorescence microscopy
dc.subjectinflammation
dc.subjectmale
dc.subjectmicroglia
dc.subjectmodulation
dc.subjectmouse
dc.subjectnervous system inflammation
dc.subjectnonhuman
dc.titlePermeation of molecules through astroglial connexin 43 hemichannels is modulated by cytokines with parameters depending on the permeant species
dc.typeArticle


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