Mineralocorticoid receptor is essential for corticosteroid-induced up-regulation of L-type calcium currents in cultured neonatal cardiomyocytes.
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 (ICa). 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 ICa. This study provides the first direct and unequivocal evidence for MR function in the heart.
Department of Pharmacology and Toxicology, University of Lausanne, Bugnon, 27, 1005 Lausanne, Switzerland.
Jean-Sébastien
JS
Rougier
Olivier
O
Muller
Stefan
S
Berger
Gabriel
G
Centeno
Günther
G
Schütz
Dmitri
D
Firsov
Hugues
H
Abriel
D000305:Adrenal Cortex Hormones / Q000378:metabolism* / Q000494:pharmacology; D000450:Aldosterone / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D003345:Corticosterone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D051379:Mice; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
D000305:Adrenal Cortex Hormones; C514350:CACNA1C protein, mouse; D020746:Calcium Channels, L-Type; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D000450:Aldosterone; D003345:Corticosterone