Mineralocorticoid receptor (MR) activation modulates cardiac L-type Ca(2+) current (I (CaL)) and transient outward K(+) current (I (to)). The exact circumstances of MR activation, however, remain elusive. Here, we investigate the influence of corticosteroids on MR-mediated changes in cellular electrophysiology. In vitro incubation of adult rat ventricular myocytes with the MR agonist aldosterone (100 nM, 24 h) increased I (CaL) density by 34% (n = 16; p < 0.01). This effect was abrogated by co-incubation with the MR antagonist spironolactone (10 muM). To investigate whether an increase in serum aldosterone concentration is sufficient for an increase in I (CaL) in vivo, rats were subjected to low Na(+) diet (LSD, 0.013% Na(+)) for 28 days. This increased serum aldosterone concentration from 0.19 +/- 0.04 nM (n = 6) in control animals (0.3% Na(+), CSD) to 16.1 +/- 2.1 nM (n = 6; p < 0.0001). Strikingly, I (CaL) density was similar in both CSD and LSD rats (-12.9 +/- 0.9 pA pF(-1), n = 18 and -13.7 +/- 1.1 pA pF(-1), n = 16, respectively), as was I (to) density. In vitro, the glucocorticoid corticosterone (1 microM) also increased I (CaL) and this effect was blocked by spironolactone (10 microM). Co-incubation with corticosterone (1 microM, the normal serum concentration) and aldosterone (100 nM, mimicking low Na(+) intake) did not further increase I (CaL) compared to corticosterone alone. Moreover, co-incubation of myocytes with N-acetylcysteine (10 mM) prevented the aldosterone (100 nM) or corticosterone (1 microM)-induced increase in I (CaL). In conclusion, an increase in serum aldosterone concentration in response to LSD is not sufficient for an increase in I (CaL) density in cardiomyocytes in vivo. This is supported in vitro by the absence of an effect of aldosterone on I (CaL) in the presence of a physiological concentration of corticosterone. Moreover, the cellular redox state may modulate MR activation.