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The Journal of Membrane Biology

, Volume 214, Issue 1–2, pp 1–8 | Cite as

Interplay between Cystic Fibrosis Transmembrane Regulator and Gap Junction Channels Made of Connexins 45, 40, 32 and 50 Expressed in Oocytes

  • Basilio A. Kotsias
  • Mohammad Salim
  • Lillian L. Peracchia
  • Camillo PeracchiaEmail author
Article

Abstract

The cystic fibrosis transmembrane regulator (CFTR) is a Cl channel known to influence other channels, including connexin (Cx) channels. To study the functional interaction between CFTR and gap junction channels, we coexpressed in Xenopus oocytes CFTR and either Cx45, Cx40, Cx32 or Cx50 and monitored junctional conductance (G j) and its sensitivity to transjunctional voltage (V j) by the dual voltage-clamp method. Application of forskolin induced a Cl current; increased G j approximately 750%, 560%, 64% and 8% in Cx45, Cx40, Cx32 and Cx50, respectively; and decreased sensitivity to V j gating, monitored by a change in the ratio between G j steady state and G j peak (G jSS/G jPK) at the pulse. In oocyte pairs expressing just Cx45 in one oocyte (#1) and both Cx45 and CFTR in the other (#2), with negative pulses applied to oocyte #1 forskolin application still increased G j and decreased the sensitivity to V j gating, indicating that CFTR activation is effective even when it affects only one of the two hemichannels and that the G j and V j changes are not artifacts of decreased membrane resistance in the pulsed oocyte. COOH-terminus truncation reduced the forskolin effect on Cx40 (Cx40TR) but not on Cx32 (Cx32TR) channels. The data suggest a cross-talk between CFTR and a variety of gap junction channels. Cytoskeletal scaffolding proteins and/or other intermediate cytoplasmic proteins are likely to play a role in CFTR-Cx interaction.

Keywords

Chloride channel Cystic fibrosis transmembrane regulator Cell communication Connexin Gap junction Channel gating Xenopus oocyte 

Notes

Acknowledgement

This study was supported by the National Institutes of Health (grant GM20113). The authors thank Dr. D. C. Devor (University of Pittsburgh, Pittsburgh, PA) for the generous gift of human CFTR cDNA.

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Basilio A. Kotsias
    • 1
  • Mohammad Salim
    • 1
  • Lillian L. Peracchia
    • 1
  • Camillo Peracchia
    • 1
    • 2
    Email author
  1. 1.Department of Pharmacology and PhysiologyUniversity of Rochester School of MedicineRochester
  2. 2.Laboratorio de NeurofisiologiaInstituto de Investigaciones Médicas, Alfredo Lanari Universidad de Buenos AiresBuenos AiresArgentina

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