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 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.
Schalper
Kurt A
KA
Departamento de Ciencias Fisiológicas, Pontificia Universidad Católica de Chile, Santiago, Chile. kschalpe@med.puc.cl
Palacios-Prado
Nicolás
N
Retamal
Mauricio A
MA
Shoji
Kenji F
KF
Martínez
Agustín D
AD
Sáez
Juan C
JC
D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D000072259:Connexin 26; D018031:Connexin 43 / Q000378:metabolism; D017630:Connexins / Q000378:metabolism*; D004594:Electrophysiology; D004789:Enzyme Activation; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D010539:Permeability; D017434:Protein Structure, Tertiary; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D018031:Connexin 43; D017630:Connexins; C000607042:GJB2 protein, human; D016220:Fibroblast Growth Factor 1; D000072259:Connexin 26; D048051:p38 Mitogen-Activated Protein Kinases; D002118:Calcium