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.
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References
Benitah JP, Vassort G (1999) Aldosterone upregulates Ca(2+) current in adult rat cardiomyocytes. Circ Res 85:1139–1145
Firsov D, Muller OG (2003) Aldosterone action in the heart. Pflugers Arch 446:328–333
Funder JW (2005) RALES, EPHESUS and redox. J Steroid Biochem Mol Biol 93:121–125
Lalevee N, Rebsamen MC, Barrere-lemaire S, Perrier E, Nargeot J, Benitah JP et al (2005) Aldosterone increases T-type calcium channel expression and in vitro beating frequency in neonatal rat cardiomyocytes. Cardiovasc Res 67:216–224
Muller O, Pradervand S, Berger S, Centeno G, Milet A, Nicod P et al (2007) Identification of corticosteroid-regulated genes in cardiomyocytes by serial analysis of gene expression. Genomics 89:370–377
Ouvrard-Pascaud A, Sainte-Marie Y, Benitah JP, Perrier R, Soukaseum C, Nguyen Dinh Cat A et al (2005) Conditional mineralocorticoid receptor expression in the heart leads to life-threatening arrhythmias. Circulation 111:3025–3033
Perrier R, Richard S, Sainte-Marie Y, Rossier BC, Jaisser F, Hummler E et al (2005) A direct relationship between plasma aldosterone and cardiac L-type Ca2+ current in mice. J Physiol (Lond) 569:153–162
Pitt B (2005) The role of aldosterone blockade in patients with heart failure. Heart Fail Rev 10:79–83
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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Rougier, JS., Muller, O., Berger, S. et al. Mineralocorticoid receptor is essential for corticosteroid-induced up-regulation of L-type calcium currents in cultured neonatal cardiomyocytes. Pflugers Arch - Eur J Physiol 456, 407–412 (2008). https://doi.org/10.1007/s00424-007-0387-z
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DOI: https://doi.org/10.1007/s00424-007-0387-z