© 1999 American Heart Association, Inc.
Cellular Biology |
Aldosterone Upregulates Ca2+ Current in Adult Rat Cardiomyocytes
From the Laboratoire de Physiopathologie Cardiovasculaire, INSERM U-390, IFR3, Montpellier, France.
Correspondence to Jean-Pierre Bénitah, INSERM U-390, CHU Arnaud de Villeneuve, 34295 Montpellier, Cedex 05, France. E-mail benitah{at}welchlink.welch.jhu.edu
Abstract—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 Ca2+ current (ICa) in isolated adult rat ventricular myocytes using the patch-clamp technique. We found that incubation of cells with 1 µmol/L aldosterone for 24 hours increases the density of ICa significantly. This "long-term" aldosterone treatment had no significant effects on the kinetics and voltage dependence of ICa inactivation. Moreover, no demonstrable influence of aldosterone on ICa 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 ICa density. These effects were also observed with lower concentrations of aldosterone (10 and 100 nmol/L). Moreover, inhibitors of transcription (actinomycin D, 5 µg/mL) and protein synthesis (cycloheximide, 20 µg/mL) prevented the aldosterone-dependent increase in ICa. Therefore, the long latency ICa stimulation effect of aldosterone might result from an increased channel expression. We suggest that this genomic action contributes to the increased ICa observed during cardiac remodeling.
Key Words: aldosterone • Ca2+current • heart
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