Aldosterone upregulates Ca2+ current in adult rat cardiomyocytes

Aldosterone is associated with the pathogenesis and progression of left ven tricular hypertrophy and heart failure, independent of its relation with ar terial blood pressure. However, little information exists about the possibl e influence of this mineralocorticoisteroid on cardiomyocyte electrical act ivity. The present study was designed to determine the role of aldosterone on whole-cell Ca2+ current (I-Ca) in isolated adult rat ventricular myocyte s using the patch-clamp technique, We found that incubation of cells with 1 mu mol/L aldosterone for 24 hours increases the density of I-Ca significan tly. This "long-term" aldosterone treatment had no significant effects on t he kinetics and voltage dependence of I-Ca inactivation. Moreover, no demon strable influence of aldosterone on I-Ca could be detected during short-ter m exposure (up to 6 hours), under our experimental conditions. The classica l aldosterone intracellular receptor antagonist spironolactone (250-fold ex cess) was able to blunt the aldosterone-induced increase in I-Ca density. T hese effects were also observed with lower concentrations of aldosterone (1 0 and 100 nmol/L). Moreover, inhibitors of transcription (actinomycin D, 5 mu g/mL) and protein synthesis (cycloheximide, 20 mu g/mL) prevented the al dosterone-dependent increase in I-Ca. Therefore, the long latency I-Ca stim ulation effect of aldosterone might result from an increased channel expres sion. We suggest that this genomic action contributes to the increased I-Ca observed during cardiac remodeling.