TY - JOUR
T1 - Connexin-based gap junction hemichannels
T2 - Gating mechanisms
AU - Sáez, Juan C.
AU - Retamal, Mauricio A.
AU - Basilio, Daniel
AU - Bukauskas, Feliksas F.
AU - Bennett, Michael V.L.
N1 - Funding Information:
This work was partially financed by a grant of Fondo Nacional para el Desarrollo de Ciencias y Tecnología (FONDECYT 1030945 to JCS), grants of the National Institute for Health (NS36706 to FFB and NS45837 to MVLB) and from the F.M. Kirby Foundation Program in Neuroprotection and Repair (to MVLB). Unpublished results on the phosphorylation and redox state on Cx43 hemichannels described here will be presented in partial fulfillment of the requirements to obtain the Ph.D. degree at the Pontificia Universidad Católica de Chile (M.A.R.).
PY - 2005/6/10
Y1 - 2005/6/10
N2 - 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.
AB - 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.
KW - Connexon
KW - Protein phosphorylation
KW - Redox potential
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U2 - 10.1016/j.bbamem.2005.01.014
DO - 10.1016/j.bbamem.2005.01.014
M3 - Review article
C2 - 15955306
AN - SCOPUS:20444413024
SN - 0005-2736
VL - 1711
SP - 215
EP - 224
JO - Biochimica et Biophysica Acta - Biomembranes
JF - Biochimica et Biophysica Acta - Biomembranes
IS - 2 SPEC. ISS.
ER -