Possible involvement of different connexin43 domains in plasma membrane permeabilization induced by ischemia-reperfusion

Mauricio A. Retamal, Kurt A. Schalper, Kenji F. Shoji, Juan A. Orellana, Michael V. L. Bennett, Juan C. Sáez

Research output: Contribution to journalArticle

42 Citations (Scopus)

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 Ca2+ 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.

Original languageEnglish (US)
Pages (from-to)49-63
Number of pages15
JournalJournal of Membrane Biology
Volume218
Issue number1-3
DOIs
StatePublished - Aug 2007

Fingerprint

Connexin 43
Reperfusion
Ischemia
Cell Membrane
Oxidation-Reduction
Cell Death
Reducing Agents
Cysteine
Connexins
Divalent Cations
Phosphorylation
Pharmacology
Membranes

Keywords

  • Connexin
  • Connexin 43
  • Hemichannel
  • Ischemia
  • Pannexin
  • Phosphorylation
  • Redox potential

ASJC Scopus subject areas

  • Biophysics
  • Physiology
  • Cell Biology

Cite this

Possible involvement of different connexin43 domains in plasma membrane permeabilization induced by ischemia-reperfusion. / Retamal, Mauricio A.; Schalper, Kurt A.; Shoji, Kenji F.; Orellana, Juan A.; Bennett, Michael V. L.; Sáez, Juan C.

In: Journal of Membrane Biology, Vol. 218, No. 1-3, 08.2007, p. 49-63.

Research output: Contribution to journalArticle

Retamal, Mauricio A. ; Schalper, Kurt A. ; Shoji, Kenji F. ; Orellana, Juan A. ; Bennett, Michael V. L. ; Sáez, Juan C. / Possible involvement of different connexin43 domains in plasma membrane permeabilization induced by ischemia-reperfusion. In: Journal of Membrane Biology. 2007 ; Vol. 218, No. 1-3. pp. 49-63.
@article{85931f1655fa4b288a46c4b6beea3cbd,
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 Ca2+ 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.",
keywords = "Connexin, Connexin 43, Hemichannel, Ischemia, Pannexin, Phosphorylation, Redox potential",
author = "Retamal, {Mauricio A.} and Schalper, {Kurt A.} and Shoji, {Kenji F.} and Orellana, {Juan A.} and Bennett, {Michael V. L.} and S{\'a}ez, {Juan C.}",
year = "2007",
month = "8",
doi = "10.1007/s00232-007-9043-y",
language = "English (US)",
volume = "218",
pages = "49--63",
journal = "Journal of Membrane Biology",
issn = "0022-2631",
publisher = "Springer New York",
number = "1-3",

}

TY - JOUR

T1 - Possible involvement of different connexin43 domains in plasma membrane permeabilization induced by ischemia-reperfusion

AU - Retamal, Mauricio A.

AU - Schalper, Kurt A.

AU - Shoji, Kenji F.

AU - Orellana, Juan A.

AU - Bennett, Michael V. L.

AU - Sáez, Juan C.

PY - 2007/8

Y1 - 2007/8

N2 - 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 Ca2+ 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.

AB - 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 Ca2+ 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.

KW - Connexin

KW - Connexin 43

KW - Hemichannel

KW - Ischemia

KW - Pannexin

KW - Phosphorylation

KW - Redox potential

UR - http://www.scopus.com/inward/record.url?scp=36248931499&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=36248931499&partnerID=8YFLogxK

U2 - 10.1007/s00232-007-9043-y

DO - 10.1007/s00232-007-9043-y

M3 - Article

C2 - 17705051

AN - SCOPUS:36248931499

VL - 218

SP - 49

EP - 63

JO - Journal of Membrane Biology

JF - Journal of Membrane Biology

SN - 0022-2631

IS - 1-3

ER -