Aldosterone upregulates Ca(2+) current in adult rat cardiomyocytes.
Aldosterone is associated with the pathogenesis and progression of left ventricular hypertrophy and heart failure, independent of its relation with arterial blood pressure. However, little information exists about the possible influence of this mineralocorticoisteroid on cardiomyocyte electrical activity. The present study was designed to determine the role of aldosterone on whole-cell Ca(2+) current (I(Ca)) in isolated adult rat ventricular myocytes using the patch-clamp technique. We found that incubation of cells with 1 micromol/L aldosterone for 24 hours increases the density of I(Ca) significantly. This "long-term" aldosterone treatment had no significant effects on the kinetics and voltage dependence of I(Ca) inactivation. Moreover, no demonstrable influence of aldosterone on I(Ca) could be detected during short-term exposure (up to 6 hours), under our experimental conditions. The classical aldosterone intracellular receptor antagonist spironolactone (250-fold excess) was able to blunt the aldosterone-induced increase in I(Ca) density. These effects were also observed with lower concentrations of aldosterone (10 and 100 nmol/L). Moreover, inhibitors of transcription (actinomycin D, 5 microg/mL) and protein synthesis (cycloheximide, 20 microg/mL) prevented the aldosterone-dependent increase in I(Ca). Therefore, the long latency I(Ca) stimulation effect of aldosterone might result from an increased channel expression. We suggest that this genomic action contributes to the increased I(Ca) observed during cardiac remodeling.
Bénitah
J P
JP
Laboratoire de Physiopathologie Cardiovasculaire, INSERM U-390, IFR3, Montpellier, France. benitah@welchlink.welch.jhu.edu
Vassort
G
G
D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology; D008297:Male; D018408:Patch-Clamp Techniques; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation / Q000187:drug effects; D016276:Ventricular Function
D011500:Protein Synthesis Inhibitors; D003609:Dactinomycin; D000450:Aldosterone; D003513:Cycloheximide; D002118:Calcium