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Mineralocorticoid receptor is essential for corticosteroid-induced up-regulation of L-type calcium currents in cultured neonatal cardiomyocytes

  • Jean-Sébastien Rougier
  • Olivier Muller
  • Stefan Berger
  • Gabriel Centeno
  • Günther Schütz
  • Dmitri FirsovEmail author
  • Hugues AbrielEmail author
Ion Channels

Abstract

Despite the fact that mineralocorticoid receptor (MR) antagonist drugs such as spironolactone and eplerenone reduce the mortality in heart failure patients, there is, thus far, no unambiguous demonstration of a functional role of MR in cardiac cells. The aim of this work was to investigate the activation pathway(s) mediating corticosteroid-induced up-regulation of cardiac calcium current (I Ca). In this study, using neonatal cardiomyocytes from MR or glucocorticoid receptor (GR) knockout (KO) mice, we show that MR is essential for corticosteroid-induced up-regulation of I Ca. This study provides the first direct and unequivocal evidence for MR function in the heart.

Keywords

Corticosteroids Nuclear receptors Aldosterone Calcium current 

Notes

Acknowledgments

This study has been funded by the Swiss National Science Foundation PP00-110638/1 (HA) and 3100AO-105592 (DF). We are grateful to Dr. Michael Harris for his helpful suggestions on this manuscript.

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Jean-Sébastien Rougier
    • 1
  • Olivier Muller
    • 2
  • Stefan Berger
    • 3
  • Gabriel Centeno
    • 1
  • Günther Schütz
    • 3
  • Dmitri Firsov
    • 1
    Email author
  • Hugues Abriel
    • 4
    • 1
    • 2
    Email author
  1. 1.Department of Pharmacology and ToxicologyUniversity of LausanneLausanneSwitzerland
  2. 2.Service of CardiologyCHUVLausanneSwitzerland
  3. 3.German Cancer Research CenterDivision Molecular Biology of the Cell IHeidelbergGermany
  4. 4.Department of Pharmacology and Toxicology, and Service of CardiologyUniversity of LausanneLausanneSwitzerland

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