Activation of the mineralocorticoid receptor (MR) in the heart has been shown to modulate the L-type Ca2+ current (ICaL ). The exact circumstances necessary for MR activation remain elusive. Incubation for 24h of adult rat left ventricular cardiac myocytes with the MR agonist aldosterone (aldo, 100 nM) increased ICaL . This effect was blocked by the specific MR antagonist spironolactone (spiro, 10 mM). The glucocorticoid corticosterone

(corti, 1 mM) increased I CaL to a similar extent, and was likewise blocked by spiro (10 mM). To mimic the physiological presence of both, glucocorticoids and aldo, myocytes were co-incubated with corti and aldo, which did not further increase ICaL compared to corti alone. To elucidate if GR activation is necessary for the increase in ICaL , myocytes were incubated with aldo or corti and the specific GR antagonist mifepristone (10mM), which abrogated their effects. The specific GR agonist RU28362 (100 nM) increased ICaL to a similar extend as corti, and was blocked by the MR antagonist spiro. The increase in ICaL was probably caused by an increase in channel number, since the degree of stimulation by BAY K8644 and forskolin was similar in controls and in myocytes incubated with aldo. In summary, both MR and GR need to be activated for an effect of aldo or corti on ICaL . However, in the presence of a physiological concentration of corti a role of aldo in the regulation of ICaL seems unlikely, even if present at high concentrations.