Connexin hemichannel composition determines the FGF-1-induced membrane permeability and free [Ca2+]i responses

Cell surface hemichannels (HCs) composed of different connexin (Cx) types are present in diverse cells and their possible role on FGF-1-induced cellular responses remains unknown. Here, we show that FGF-1 transiently (4-14 h, maximal at 7 h) increases the membrane permeability through HCs in HeLa ce...

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Bibliographic Details
Published in:Molecular biology of the cell 2008-08, Vol.19 (8), p.3501-3513
Main Authors: Schalper, Kurt A, Palacios-Prado, Nicolás, Retamal, Mauricio A, Shoji, Kenji F, Martínez, Agustín D, Sáez, Juan C
Format: Article
Language:English
Subjects:
Calcium - metabolism
Cell Membrane - metabolism
Connexin 26
Connexin 43 - metabolism
Connexins - metabolism
Electrophysiology
Enzyme Activation
Fibroblast Growth Factor 1 - metabolism
HeLa Cells
Humans
Microscopy, Fluorescence
Models, Biological
p38 Mitogen-Activated Protein Kinases - metabolism
Permeability
Protein Structure, Tertiary
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Summary:Cell surface hemichannels (HCs) composed of different connexin (Cx) types are present in diverse cells and their possible role on FGF-1-induced cellular responses remains unknown. Here, we show that FGF-1 transiently (4-14 h, maximal at 7 h) increases the membrane permeability through HCs in HeLa cells expressing Cx43 or Cx45 under physiological extracellular Ca(2+)/Mg(2+) concentrations. The effect does not occur in HeLa cells expressing HCs constituted of Cx26 or Cx43 with its C-terminus truncated at aa 257, or in parental nontransfected HeLa cells. The increase in membrane permeability is associated with a rise in HC levels at the cell surface and a proportional increase in HC unitary events. The response requires an early intracellular free Ca(2+) concentration increase, activation of a p38 MAP kinase-dependent pathway, and a regulatory site of Cx subunit C-terminus. The FGF-1-induced rise in membrane permeability is also associated with a late increase in intracellular free Ca(2+) concentration, suggesting that responsive HCs allow Ca(2+) influx. The cell density of Cx26 and Cx43 HeLa transfectants cultured in serum-free medium was differentially affected by FGF-1. Thus, the FGF-1-induced cell permeabilization and derived consequences depend on the Cx composition of HCs.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.E07-12-1240