title: Possible involvement of different connexin43 domains in plasma membrane permeabilization induced by ischemia-reperfusion.
abstract: In vitro and in vivo studies support the involvement of connexin 43-based cell-cell channels and hemichannels in cell death propagation induced by ischemia-reperfusion. In this context, open connexin hemichannels in the plasma membrane have been proposed to act as accelerators of cell death. Progress on the mechanisms underlying the cell permeabilization induced by ischemia-reperfusion reveals the involvement of several factors leading to an augmented open probability and increased number of hemichannels on the cell surface. While open probability can be increased by a reduction in extracellular concentration of divalent cations and changes in covalent modifications of connexin 43 (oxidation and phosphorylation), increase in number of hemichannels requires an elevation of the intracellular free Ca(2+) concentration. Reversal of connexin 43 redox changes and membrane permeabilization can be induced by intracellular, but not extracellular, reducing agents, suggesting a cytoplasmic localization of the redox sensor(s). In agreement, hemichannels formed by connexin 45, which lacks cytoplasmic cysteines, or by connexin 43 with its C-terminal domain truncated to remove its cysteines are insensitive to reducing agents. Although further studies are required for a precise localization of the redox sensor of connexin 43 hemichannels, modulation of the redox potential is proposed as a target for the design of pharmacological tools to reduce cell death induced by ischemia-reperfusion in connexin 43-expressing cells.
authors: Departamento de Ciencias Fisiológicas, Pontificia Universidad Católica de Chile, Alameda 340, Santiago, Chile.
authors: Mauricio A
authors: MA
authors: Retamal
authors: Kurt A
authors: KA
authors: Schalper
authors: Kenji F
authors: KF
authors: Shoji
authors: Juan A
authors: JA
authors: Orellana
authors: Michael V L
authors: MV
authors: Bennett
authors: Juan C
authors: JC
authors: Sáez
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D002463:Cell Membrane Permeability; D018031:Connexin 43 / Q000502:physiology*; D006801:Humans; D007473:Ion Channels / Q000502:physiology*; D015427:Reperfusion Injury / Q000378:metabolism*
chemical_list: D018031:Connexin 43; D007473:Ion Channels
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