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 (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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adrenal Cortex Hormones / metabolism*
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Adrenal Cortex Hormones / pharmacology
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Aldosterone / pharmacology
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Animals
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Animals, Newborn
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Calcium Channels, L-Type / drug effects
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Calcium Channels, L-Type / metabolism*
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Cells, Cultured
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Corticosterone / pharmacology
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Dose-Response Relationship, Drug
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Mice
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Mice, Knockout
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Myocytes, Cardiac / cytology
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Myocytes, Cardiac / metabolism*
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Patch-Clamp Techniques
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RNA, Messenger / metabolism
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Receptors, Glucocorticoid / drug effects
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Receptors, Glucocorticoid / genetics
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Receptors, Glucocorticoid / metabolism
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Receptors, Mineralocorticoid / drug effects
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Receptors, Mineralocorticoid / genetics
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Receptors, Mineralocorticoid / metabolism*
Substances
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Adrenal Cortex Hormones
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CACNA1C protein, mouse
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Calcium Channels, L-Type
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RNA, Messenger
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Receptors, Glucocorticoid
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Receptors, Mineralocorticoid
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Aldosterone
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Corticosterone