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Open AccessArticle

Permeation of Molecules through Astroglial Connexin 43 Hemichannels Is Modulated by Cytokines with Parameters Depending on the Permeant Species

1
Departamento de Fisiología, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile
2
Instituto de Neurociencias, Centro Interdisciplinario de Neurociencias de Valparaíso, Universidad de Valparaíso, Valparaíso 2381850, Chile
3
Instituto de Ciencias de la Salud, Universidad de O′Higgins, Rancagua 2820000, Chile
4
Mechanisms on Myelin Formation and Repair Laboratory, Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Santiago 8910060, Chile
5
Center for Interdisciplinary Research in Biology (CIRB), College de France, CNRS, INSERM, PSL Research University, 75005 Paris, France
6
Departamento de Neurología, Escuela de Medicina and Centro Interdisciplinario de Neurociencias, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(11), 3970; https://doi.org/10.3390/ijms21113970
Received: 30 April 2020 / Revised: 25 May 2020 / Accepted: 29 May 2020 / Published: 1 June 2020
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-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. View Full-Text
Keywords: connexons; dyes; permeability tracers; permeation; TNF-α; IL-1β; astrocytes connexons; dyes; permeability tracers; permeation; TNF-α; IL-1β; astrocytes
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MDPI and ACS Style

Sáez, J.C.; Vargas, A.A.; Hernández, D.E.; Ortiz, F.C.; Giaume, C.; Orellana, J.A. Permeation of Molecules through Astroglial Connexin 43 Hemichannels Is Modulated by Cytokines with Parameters Depending on the Permeant Species. Int. J. Mol. Sci. 2020, 21, 3970. https://doi.org/10.3390/ijms21113970

AMA Style

Sáez JC, Vargas AA, Hernández DE, Ortiz FC, Giaume C, Orellana JA. Permeation of Molecules through Astroglial Connexin 43 Hemichannels Is Modulated by Cytokines with Parameters Depending on the Permeant Species. International Journal of Molecular Sciences. 2020; 21(11):3970. https://doi.org/10.3390/ijms21113970

Chicago/Turabian Style

Sáez, Juan C.; Vargas, Aníbal A.; Hernández, Diego E.; Ortiz, Fernando C.; Giaume, Christian; Orellana, Juan A. 2020. "Permeation of Molecules through Astroglial Connexin 43 Hemichannels Is Modulated by Cytokines with Parameters Depending on the Permeant Species" Int. J. Mol. Sci. 21, no. 11: 3970. https://doi.org/10.3390/ijms21113970

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