Modulation of brain hemichannels and gap junction channels by pro-inflammatory agents and their possible role in neurodegeneration

Juan A. Orellana, Pablo J. Sáez, Kenji F. Shoji, Kurt A. Schalper, Nicolás Palacios-Prado, Victoria Velarde, Christian Giaume, Michael V. L. Bennett, Juan C. Sáez

Research output: Contribution to journalArticle

156 Citations (Scopus)

Abstract

In normal brain, neurons, astrocytes, and oligodendrocytes, the most abundant and active cells express pannexins and connexins, protein subunits of two families forming membrane channels. Most available evidence indicates that in mammals endogenously expressed pannexins form only hemichannels and connexins form both gap junction channels and hemichannels. Whereas gap junction channels connect the cytoplasm of contacting cells and coordinate electric and metabolic activity, hemichannels communicate the intra- and extracellular compartments and serve as a diffusional pathway for ions and small molecules. A subthreshold stimulation by acute pathological threatening conditions (e.g., global ischemia subthreshold for cell death) enhances neuronal Cx36 and glial Cx43 hemichannel activity, favoring ATP release and generation of preconditioning. If the stimulus is sufficiently deleterious, microglia become overactivated and release bioactive molecules that increase the activity of hemichannels and reduce gap junctional communication in astroglial networks, depriving neurons of astrocytic protective functions, and further reducing neuronal viability. Continuous glial activation triggered by low levels of anomalous proteins expressed in several neurodegenerative diseases induce glial hemichannel and gap junction channel disorders similar to those of acute inflammatory responses triggered by ischemia or infectious diseases. These changes are likely to occur in diverse cell types of the CNS and contribute to neurodegeneration during inflammatory process.

Original languageEnglish (US)
Pages (from-to)369-399
Number of pages31
JournalAntioxidants and Redox Signaling
Volume11
Issue number2
DOIs
StatePublished - Feb 1 2009

Fingerprint

Gap Junctions
Neuroglia
Brain
Connexins
Modulation
Neurons
Ischemia
Neurodegenerative diseases
Connexin 43
Molecules
Mammals
Oligodendroglia
Protein Subunits
Microglia
Cell death
Ion Channels
Astrocytes
Neurodegenerative Diseases
Communicable Diseases
Cytoplasm

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Physiology
  • Clinical Biochemistry

Cite this

Orellana, J. A., Sáez, P. J., Shoji, K. F., Schalper, K. A., Palacios-Prado, N., Velarde, V., ... Sáez, J. C. (2009). Modulation of brain hemichannels and gap junction channels by pro-inflammatory agents and their possible role in neurodegeneration. Antioxidants and Redox Signaling, 11(2), 369-399. https://doi.org/10.1089/ars.2008.2130

Modulation of brain hemichannels and gap junction channels by pro-inflammatory agents and their possible role in neurodegeneration. / Orellana, Juan A.; Sáez, Pablo J.; Shoji, Kenji F.; Schalper, Kurt A.; Palacios-Prado, Nicolás; Velarde, Victoria; Giaume, Christian; Bennett, Michael V. L.; Sáez, Juan C.

In: Antioxidants and Redox Signaling, Vol. 11, No. 2, 01.02.2009, p. 369-399.

Research output: Contribution to journalArticle

Orellana, JA, Sáez, PJ, Shoji, KF, Schalper, KA, Palacios-Prado, N, Velarde, V, Giaume, C, Bennett, MVL & Sáez, JC 2009, 'Modulation of brain hemichannels and gap junction channels by pro-inflammatory agents and their possible role in neurodegeneration', Antioxidants and Redox Signaling, vol. 11, no. 2, pp. 369-399. https://doi.org/10.1089/ars.2008.2130
Orellana, Juan A. ; Sáez, Pablo J. ; Shoji, Kenji F. ; Schalper, Kurt A. ; Palacios-Prado, Nicolás ; Velarde, Victoria ; Giaume, Christian ; Bennett, Michael V. L. ; Sáez, Juan C. / Modulation of brain hemichannels and gap junction channels by pro-inflammatory agents and their possible role in neurodegeneration. In: Antioxidants and Redox Signaling. 2009 ; Vol. 11, No. 2. pp. 369-399.
@article{29294aa858534e0cadc7f9aecc28dadb,
title = "Modulation of brain hemichannels and gap junction channels by pro-inflammatory agents and their possible role in neurodegeneration",
abstract = "In normal brain, neurons, astrocytes, and oligodendrocytes, the most abundant and active cells express pannexins and connexins, protein subunits of two families forming membrane channels. Most available evidence indicates that in mammals endogenously expressed pannexins form only hemichannels and connexins form both gap junction channels and hemichannels. Whereas gap junction channels connect the cytoplasm of contacting cells and coordinate electric and metabolic activity, hemichannels communicate the intra- and extracellular compartments and serve as a diffusional pathway for ions and small molecules. A subthreshold stimulation by acute pathological threatening conditions (e.g., global ischemia subthreshold for cell death) enhances neuronal Cx36 and glial Cx43 hemichannel activity, favoring ATP release and generation of preconditioning. If the stimulus is sufficiently deleterious, microglia become overactivated and release bioactive molecules that increase the activity of hemichannels and reduce gap junctional communication in astroglial networks, depriving neurons of astrocytic protective functions, and further reducing neuronal viability. Continuous glial activation triggered by low levels of anomalous proteins expressed in several neurodegenerative diseases induce glial hemichannel and gap junction channel disorders similar to those of acute inflammatory responses triggered by ischemia or infectious diseases. These changes are likely to occur in diverse cell types of the CNS and contribute to neurodegeneration during inflammatory process.",
author = "Orellana, {Juan A.} and S{\'a}ez, {Pablo J.} and Shoji, {Kenji F.} and Schalper, {Kurt A.} and Nicol{\'a}s Palacios-Prado and Victoria Velarde and Christian Giaume and Bennett, {Michael V. L.} and S{\'a}ez, {Juan C.}",
year = "2009",
month = "2",
day = "1",
doi = "10.1089/ars.2008.2130",
language = "English (US)",
volume = "11",
pages = "369--399",
journal = "Antioxidants and Redox Signaling",
issn = "1523-0864",
publisher = "Mary Ann Liebert Inc.",
number = "2",

}

TY - JOUR

T1 - Modulation of brain hemichannels and gap junction channels by pro-inflammatory agents and their possible role in neurodegeneration

AU - Orellana, Juan A.

AU - Sáez, Pablo J.

AU - Shoji, Kenji F.

AU - Schalper, Kurt A.

AU - Palacios-Prado, Nicolás

AU - Velarde, Victoria

AU - Giaume, Christian

AU - Bennett, Michael V. L.

AU - Sáez, Juan C.

PY - 2009/2/1

Y1 - 2009/2/1

N2 - In normal brain, neurons, astrocytes, and oligodendrocytes, the most abundant and active cells express pannexins and connexins, protein subunits of two families forming membrane channels. Most available evidence indicates that in mammals endogenously expressed pannexins form only hemichannels and connexins form both gap junction channels and hemichannels. Whereas gap junction channels connect the cytoplasm of contacting cells and coordinate electric and metabolic activity, hemichannels communicate the intra- and extracellular compartments and serve as a diffusional pathway for ions and small molecules. A subthreshold stimulation by acute pathological threatening conditions (e.g., global ischemia subthreshold for cell death) enhances neuronal Cx36 and glial Cx43 hemichannel activity, favoring ATP release and generation of preconditioning. If the stimulus is sufficiently deleterious, microglia become overactivated and release bioactive molecules that increase the activity of hemichannels and reduce gap junctional communication in astroglial networks, depriving neurons of astrocytic protective functions, and further reducing neuronal viability. Continuous glial activation triggered by low levels of anomalous proteins expressed in several neurodegenerative diseases induce glial hemichannel and gap junction channel disorders similar to those of acute inflammatory responses triggered by ischemia or infectious diseases. These changes are likely to occur in diverse cell types of the CNS and contribute to neurodegeneration during inflammatory process.

AB - In normal brain, neurons, astrocytes, and oligodendrocytes, the most abundant and active cells express pannexins and connexins, protein subunits of two families forming membrane channels. Most available evidence indicates that in mammals endogenously expressed pannexins form only hemichannels and connexins form both gap junction channels and hemichannels. Whereas gap junction channels connect the cytoplasm of contacting cells and coordinate electric and metabolic activity, hemichannels communicate the intra- and extracellular compartments and serve as a diffusional pathway for ions and small molecules. A subthreshold stimulation by acute pathological threatening conditions (e.g., global ischemia subthreshold for cell death) enhances neuronal Cx36 and glial Cx43 hemichannel activity, favoring ATP release and generation of preconditioning. If the stimulus is sufficiently deleterious, microglia become overactivated and release bioactive molecules that increase the activity of hemichannels and reduce gap junctional communication in astroglial networks, depriving neurons of astrocytic protective functions, and further reducing neuronal viability. Continuous glial activation triggered by low levels of anomalous proteins expressed in several neurodegenerative diseases induce glial hemichannel and gap junction channel disorders similar to those of acute inflammatory responses triggered by ischemia or infectious diseases. These changes are likely to occur in diverse cell types of the CNS and contribute to neurodegeneration during inflammatory process.

UR - http://www.scopus.com/inward/record.url?scp=58149100746&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58149100746&partnerID=8YFLogxK

U2 - 10.1089/ars.2008.2130

DO - 10.1089/ars.2008.2130

M3 - Article

C2 - 18816186

AN - SCOPUS:58149100746

VL - 11

SP - 369

EP - 399

JO - Antioxidants and Redox Signaling

JF - Antioxidants and Redox Signaling

SN - 1523-0864

IS - 2

ER -