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Cited by 244Connexins and lens biologyCell death mechanisms and regulationCardiac Ischemia and Reperfusion

Role of connexin-based gap junction channels and hemichannels in ischemia-induced cell death in nervous tissue

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Contreras, Jorge E., Sánchez, Helmuth A., Véliz, Loreto P., Bukauskas, Feliksas F., Bennett, Michael V.L., Sáez, Juan C.·2004·Brain Research Reviews
DOI 10.1016/j.brainresrev.2004.08.002PMC PMC3651737
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Abstract

Gap junction channels and hemichannels formed of connexin subunits are found in most cell types in vertebrates. Gap junctions connect cells via channels not open to the extracellular space and permit the passage of ions and molecules of approximately 1 kDa. Single connexin hemichannels, which are connexin hexamers, are present in the surface membrane before docking with a hemichannel in an apposed membrane. Because of their high conductance and permeability in cell-cell channels, it had been thought that connexin hemichannels remained closed until docking to form a cell-cell channel. Now it is clear that at least some hemichannels can open to allow passage of molecules between the cytoplasm and extracellular space. Here we review evidence that gap junction channels may allow intercellular diffusion of necrotic or apoptotic signals, but may also allow diffusion of ions and substances from healthy to injured cells, thereby contributing to cell survival. Moreover, opening of gap junction hemichannels may exacerbate cell injury or mediate paracrine or autocrine signaling. In addition to the cell specific features of an ischemic insult, propagation of cell damage and death within affected tissues may be affected by expression and regulation of gap junction channels and hemichannels formed by connexins.

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  • Little permeability of membranes within 40 min of ischemia to low molecular weight dyes suggests that substances such as ATP and other intracellular constituents that appear extracellularly are not released through wide-spread loss of membrane integrity in vivo.

    “Our results showing little permeability of membranes within 40 min of ischemia to low molecular weight dyes suggests that substances such as ATP and other intracellular constituents that appear extracellularly are not released through wide-spread loss of membrane integrity in vivo (Contreras et al., 2004).”

    From Two-Photon Imaging of Stroke Onset<i>In Vivo</i>Reveals That NMDA-Receptor Independent Ischemic Depolarization Is the Major Cause of Rapid Reversible Damage to Dendrites and Spines (2008) · cites this paper as Contreras et al., 2004

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Authors
Contreras, J. E., Sánchez, H. A., Véliz, L. P., Bukauskas, F. F., Bennett, M. V. L., & Sáez, J. C.
Affiliations
  • Pontificia Universidad Católica de Chile (CL)
  • Albert Einstein College of Medicine (US)
Corresponding author
Sánchez, Helmuth A.
ORCID
Venue
Brain Research Reviews
Publisher
Elsevier BV
Published
2004-12
Volume
47
Issue
1-3
Pages
290-303
ISSN
0165-0173 (ISSN-L)
DOI
10.1016/j.brainresrev.2004.08.002
PMC
PMC3651737
OpenAlex
W2064197300
Cited by
244
References
162
Citations by year
2026: 5 · 2025: 4 · 2024: 5 · 2023: 4 · 2022: 7 · 2021: 5 · 2020: 9 · 2019: 7 · 2018: 10 · 2017: 14 · 2016: 10 · 2015: 11 · 2014: 20 · 2013: 15 · 2012: 13
FWCI
0.74
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Brain Research Reviews (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Americanae (AECID Library) (submittedVersion, other-oa)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
Funders
  • Fondo Nacional de Ciencia y Tecnología
  • National Institutes of Health
  • National Institute of Neurological Disorders and Stroke (R01NS036706, NS45837, NS 36706, R21NS045837)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
Keywords
connexins, gap junction channels, connexin hemichannels, neuronal injury, intercellular communication, paracrine signaling, autocrine signaling, apoptosis, necrosis, cell survival
MeSH terms
Animals, Brain, Cell Communication, Brain Ischemia, Diffusion, Extracellular Space, Humans, Signal Transduction, Cell Death, Gap Junctions, Connexins

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