Cell membrane permeabilization via connexin hemichannels in living and dying cells

• Published in: Experimental cell research 2010-09, Vol.316 (15), p.2377-2389
• Main Authors: Sáez, Juan C., Schalper, Kurt A., Retamal, Mauricio A., Orellana, Juan A., Shoji, Kenji F., Bennett, Michael V.L
• Format: Article
• Language: English
• Subjects: [Ca 2+] i; Animals; Cell Death - genetics; Cell Death - physiology; Cell Membrane Permeability - genetics; Cell Membrane Permeability - physiology; Cell Survival - genetics; Cell Survival - physiology; Cellular biology; Connexins - chemistry; Connexins - genetics; Connexins - metabolism; Connexins - physiology; Connexons; Gating; Humans; Ion Channel Gating - genetics; Ion Channel Gating - physiology; Ion Channels - chemistry; Ion Channels - genetics; Ion Channels - metabolism; Ion Channels - physiology; Membranes; Models, Biological; Permeability; Phosphorylation; Potentiation; Protein Binding - physiology; Proteins; Redox; Signal transduction; Structure-Activity Relationship; Surface protein; Voltage
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2010.05.026

Vertebrate cells that express connexins likely express connexin hemichannels (Cx HCs) at their surface. In diverse cell types, surface Cx HCs can open to serve as a diffusional exchange pathway for ions and small molecules across the cell membrane. Most cells, if not all, also express pannexins that form hemichannels and increase the cell membrane permeability but are not addressed in this review. To date, most characterizations of Cx HCs have utilized cultured cells under resting conditions have and revealed low open probability and unitary conductance close to double that of the corresponding gap junction channels. In addition, the cell membrane permeability through Cx HCs can be markedly affected within seconds to minutes by various changes in the intra and/or extracellular microenvironment (i.e., pH, pCa, redox state, transmembrane voltage and intracellular regulatory proteins) that affect levels, open probability and/or (single channel) permeability of Cx HC. Net increase or decrease in membrane permeability could result from the simultaneous interaction of different mechanisms that affect hemichannels. The permeability of Cx HCs is controlled by complex signaling cascades showing connexin, cell and cell stage dependency. Changes in membrane permeability via hemichannels can have positive consequences in some cells (mainly in healthy cells), whereas in others (mainly in cells affected by acquired and/or genetic diseases) hemichannel activation can be detrimental.