Connexin-based gap junction hemichannels: Gating mechanisms

Juan C. Sáez, Mauricio A. Retamal, Daniel Basilio, Feliksas F. Bukauskas, Michael V. L. Bennett

Research output: Contribution to journalArticle

279 Citations (Scopus)

Abstract

Connexins (Cxs) form hemichannels and gap junction channels. Each gap junction channel is composed of two hemichannels, also termed connexons, one from each of the coupled cells. Hemichannels are hexamers assembled in the ER, the Golgi, or a post Golgi compartment. They are transported to the cell surface in vesicles and inserted by vesicle fusion, and then dock with a hemichannel in an apposed membrane to form a cell-cell channel. It was thought that hemichannels should remain closed until docking with another hemichannel because of the leak they would provide if their permeability and conductance were like those of their corresponding cell-cell channels. Now it is clear that hemichannels formed by a number of different connexins can open in at least some cells with a finite if low probability, and that their opening can be modulated under various physiological and pathological conditions. Hemichannels open in different kinds of cells in culture with conductance and permeability properties predictable from those of the corresponding gap junction channels. Cx43 hemichannels are preferentially closed in cultured cells under resting conditions, but their open probability can be increased by the application of positive voltages and by changes in protein phosphorylation and/or redox state. In addition, increased activity can result from the recruitment of hemichannels to the plasma membrane as seen in metabolically inhibited astrocytes. Mutations of connexins that increase hemichannel open probability may explain cellular degeneration in several hereditary diseases. Taken together, the data indicate that hemichannels are gated by multiple mechanisms that independently or cooperatively affect their open probability under physiological as well as pathological conditions.

Original languageEnglish (US)
Pages (from-to)215-224
Number of pages10
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1711
Issue number2 SPEC. ISS.
DOIs
StatePublished - Jun 10 2005

Fingerprint

Connexins
Gap Junctions
Connexin 43
Phosphorylation
Docks
Cell membranes
Permeability
Fusion reactions
Cells
Inborn Genetic Diseases
Membranes
Astrocytes
Electric potential
Oxidation-Reduction
Cultured Cells
Cell Culture Techniques
Cell Membrane
Proteins
Mutation

Keywords

  • Connexon
  • Protein phosphorylation
  • Redox potential

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Biophysics

Cite this

Connexin-based gap junction hemichannels : Gating mechanisms. / Sáez, Juan C.; Retamal, Mauricio A.; Basilio, Daniel; Bukauskas, Feliksas F.; Bennett, Michael V. L.

In: Biochimica et Biophysica Acta - Biomembranes, Vol. 1711, No. 2 SPEC. ISS., 10.06.2005, p. 215-224.

Research output: Contribution to journalArticle

Sáez, Juan C. ; Retamal, Mauricio A. ; Basilio, Daniel ; Bukauskas, Feliksas F. ; Bennett, Michael V. L. / Connexin-based gap junction hemichannels : Gating mechanisms. In: Biochimica et Biophysica Acta - Biomembranes. 2005 ; Vol. 1711, No. 2 SPEC. ISS. pp. 215-224.
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