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Pflügers Archiv

, Volume 434, Issue 1, pp 113–116 | Cite as

Reversible inhibition of gap junctional communication by tamoxifen in cultured cardiac myocytes

  • Franck Verrecchia
  • J.-C. Hervé
ORIGINAL ARTICLE

Abstract

 Gap junction channels provide a cell-to-cell conduction pathway for direct exchange of ions and small molecules. The intercellular diffusion of a fluorescent dye, quantified in cardiac myocytes from neonatal rats by monitoring the fluorescence recovery after photobleaching, was found to be interrupted after short-term exposure (15 min) to tamoxifen, an anti-oestrogen drug often used in the treatment of human breast cancer. This diffusional uncoupling was dose dependent, occurred in the concentration range 3–25 μM and reversed after tamoxifen withdrawal. Some possible mechanisms of junctional channel closure have been examined. The cytosolic calcium concentration, examined using the fluorescent indicator Indo-1, did not vary during the short-term action of tamoxifen. A second anti-oestrogen agent (clomiphene) was able to impair gap junctional communication, whereas a third (nafoxidine) had no effect. Protein-kinase-C-inhibitor properties of tamoxifen did not seem to be involved in its uncoupling action. The characteristics of tamoxifen’s action (i.e. channel inhibition delay, active concentration range, reversibility, etc.) were very similar to the previously observed effects of several other lipophilic compounds (e.g. 17β-oestradiol, etc.) on junctional channels, and to recently reported effects of tamoxifen on voltage-gated calcium currents.

Key words Diffusional coupling Intracellular calcium Photobleaching Protein kinase C Anti-oestrogen compounds 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • Franck Verrecchia
    • 1
  • J.-C. Hervé
    • 1
  1. 1.Laboratoire de Physiologie Cellulaire, Unité de Recherche Associée au CNRS no. 1869, 40, avenue du R. Pineau, F-86022 Poitiers, FranceFR

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