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Cardiac connexins Cx43 and Cx45: formation of diverse gap junction channels with diverse electrical properties

  • Cell and Molecular Physiology
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Abstract

HeLa cells expressing rat connexin43 (Cx43) and/or mouse Cx45 were studied with the dual voltage-clamp technique. Different types of cell pairs were established and their gap junction properties determined, i.e. the dependence of the instantaneous and steady-state conductances (g j,inst, g j,ss) on the transjunctional voltage (V j) and the kinetics of inactivation of the gap junction current (I j). Pairs of singly transfected cells showed homogeneous behaviour at both V j polarities. Homotypic Cx43-Cx43 and Cx45-Cx45 cell pairs yielded distinct symmetrical functions g j,inst=f(V j) and g j,ss=f(V j). Heterotypic Cx43-Cx45 preparations exhibited asymmetric functions g j,inst=f(V j) and g j,ss=f(V j) suggesting that connexons Cx43 and Cx45 gate with positive and negative V j, respectively. Preparations containing a singly (Cx43 or Cx45) or doubly (Cx43/45) transfected cell showed quasi-homogeneous behaviour at one V j polarity and heterogeneous behaviour at the other polarity. The former yielded Boltzmann parameters intermediate between those of Cx43-Cx43, Cx45-Cx45 and Cx43-Cx45 preparations; the latter could not be explained by homotypic and heterotypic combinations of homomeric connexons. Each pair of doubly transfected cells (Cx43/Cx45) yielded unique functions g j,inst=f(V j) and g j,ss=f(V j). This can not be explained by combinations of homomeric connexons. We conclude that Cx43 and Cx45 form homomeric-homotypic, homomeric-heterotypic channels as well as heteromeric-homotypic and heteromeric-heterotypic channels. This has implications for the impulse propagation in specific areas of the heart.

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Acknowledgements

We thank the laboratory of K. Willecke, Institut für Genetik, Bonn, Germany, for providing some transfected cells. We are grateful to D. Lüthi for expert technical assistance. This work was supported by grants of the Bundesamt für Bildung und Wissenschaft (code 99.0368-1; code EU grant: QLG1-GT-199-00516) and the Swiss National Science Foundation (31-55297.98 and 31-67230.01).

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Authors and Affiliations

  1. Physiologisches Institut, Universität Bern, Bühlplatz 5, 3012, Bern, Switzerland

    Thomas Desplantez & Robert Weingart

  2. National Heart and Lung Institute (Imperial College London), Royal Brompton Hospital, Sydney Street, London, SW3 6NP, UK

    Deborah Halliday & Emmanuel Dupont

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  1. Thomas Desplantez
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  2. Deborah Halliday
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  3. Emmanuel Dupont
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  4. Robert Weingart
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Correspondence to Robert Weingart.

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Desplantez, T., Halliday, D., Dupont, E. et al. Cardiac connexins Cx43 and Cx45: formation of diverse gap junction channels with diverse electrical properties. Pflugers Arch - Eur J Physiol 448, 363–375 (2004). https://doi.org/10.1007/s00424-004-1250-0

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