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.
Rougier
Jean-Sébastien
JS
Department of Pharmacology and Toxicology, University of Lausanne, Bugnon, 27, 1005 Lausanne, Switzerland.
Muller
Olivier
O
Berger
Stefan
S
Centeno
Gabriel
G
Schütz
Günther
G
Firsov
Dmitri
D
Abriel
Hugues
H
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