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Vol. 19, Issue 8, 3501-3513, August 2008

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Connexin Hemichannel Composition Determines the FGF-1–induced Membrane Permeability and Free [Ca²⁺]_i Responses

Kurt A. Schalper^*, Nicolás Palacios-Prado^*, Mauricio A. Retamal^*, Kenji F. Shoji^*, Agustín D. Martínez, and Juan C. Sáez^*,

*Departamento de Ciencias Fisiológicas, Núcleo Milenio Inmunología e Inmunoterapia, Pontificia Universidad Católica de Chile, Santiago, Chile; and Centro de Neurociencias de Valparaíso, Universidad de Valparaíso, Valparaíso, Chile

Submitted December 13, 2007; Revised April 8, 2008; Accepted May 8, 2008
Monitoring Editor: Asma Nusrat

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 Ca²⁺/Mg²⁺ 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 Ca²⁺ 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 Ca²⁺ concentration, suggesting that responsive HCs allow Ca²⁺ 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.

Address correspondence to: Kurt A. Schalper (kschalpe{at}med.puc.cl).

Abbreviations used: Cx, connexin; Px, pannexin; Etd, ethidium; FGF-1, acidic fibroblast growth factor; FGFR, fibroblast growth factor receptor; 18β-GA, 18β-glycerrithinic acid.

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