Browsing by Author "Hernández, Diego E."

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    Axonal degeneration induced by glutamate excitotoxicity is mediated by necroptosis
    (2018) Hernández, Diego E.; Salvadores, Natalia A.; Moya Alvarado, Guillermo Adrián; Catalán, Romina J.; Bronfman C., Francisca; Court G., Felipe
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    Permeation of molecules through astroglial connexin 43 hemichannels is modulated by cytokines with parameters depending on the permeant species
    (2020) Sáez, Juan Carlos; Vargas, Aníbal A.; Hernández, Diego E.; Ortiz, Fernando C.; Giaume, Christian; Orellana Roca, Juan Andrés
    Recent 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-1 beta plus TNF-alpha, a well-known pro-inflammatory condition that activates astroglial connexin 43 (Cx43) hemichannels, could alter their permeability to molecules. We found that IL-1 beta plus TNF-alpha 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 K-d (Etd, DAPI, YO-PRO-1 or 2-NBDG) and Hill coefficients (Etd and YO-PRO-1), but not in alterations of V-max. We speculate that IL-1 beta plus TNF-alpha may distinctively affect the binding sites to permeants in astroglial Cx43 hemichannels rather than their number in the cell surface. Alternatively, IL-1 beta plus TNF-alpha 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.