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Regulation of T-type Cav3.1 channels expression by synthetic glucocorticoid dexamethasone in neonatal cardiac myocytes

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Abstract

The effect of the dexamethasone (Dex) on the regulation of the T-type Ca2+ channel expressions was investigated in primary cultures of neonatal rat ventricular myocytes. We found that Dex (1 μM) increases the T-type Ca2+ current (ICaT) associated with an increase in Cav3.1 mRNA amount. We isolated the upstream region from Cav3.1 encoding gene and tested the activity of the promoter in transfected ventricular myocytes. We found a minimal Dex-responsive region that displayed putative glucocorticoid receptor (GR) and nuclear factor kappa-B (NFκB) targets. The GR selective antagonist, RU38486 (10 μM), nearly turned off the transcriptional activity of Cav3.1 encoding gene, and an NFκB inhibitor, pyrrolodine dithiocarbonate (10 μM), completely abolished the Dex-induced mRNA increase. However, Dex-induced GR and NFκB synthesis and nuclear translocation were not timely related to Cav3.1 mRNA increase. These results indicate that both GR and NFκB were necessary, but not sufficient, to trigger the increase in Cav3.1 mRNA amount. This study showed the relationship between glucocorticoid and T-type channels up-regulation that may be involved in cardiac development and pathology.

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Acknowledgements

This work was supported by the Centre National de la Recherche Scientifique, the Centre Chirurgical Marie Lannelongue and the Association Française contre la Myopathie (Contracts D10581A/S01091 and F11898A/S01091). The corresponding author is a Ph.D student affiliated to the University Paris Descartes.

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Authors and Affiliations

  1. CNRS UMR 8162––Université Paris-Sud XI, Hôpital Marie Lannelongue, 133 avenue de la Résistance, 92350, Le Plessis Robinson, France

    Fatima BenMohamed, Yann Ruchon, Elodie Gouadon, Jean-François Renaud & Véronique Capuano

  2. Laboratory of Cellular and Molecular Neuroscience, Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK

    Laurent Ferron

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  1. Fatima BenMohamed
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Correspondence to Fatima BenMohamed.

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BenMohamed, F., Ferron, L., Ruchon, Y. et al. Regulation of T-type Cav3.1 channels expression by synthetic glucocorticoid dexamethasone in neonatal cardiac myocytes. Mol Cell Biochem 320, 173–183 (2009). https://doi.org/10.1007/s11010-008-9919-x

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