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Aldosterone upregulates Ca(2+) current in adult rat cardiomyocytes
1Laboratoire de Physiopathologie Cardiovasculaire, INSERM U-390, IFR3, Montpellier, France. benitah@welchlink.welch.jhu.edu
Insights
Aldosterone significantly increases cardiomyocyte calcium current (I(Ca)) density over 24 hours, suggesting a genomic mechanism. This finding offers insights into aldosterone
Area of Science:
- Cardiovascular Physiology
- Molecular Endocrinology
- Cardiac Electrophysiology
Background:
- Aldosterone contributes to left ventricular hypertrophy and heart failure, independent of blood pressure.
- Limited data exists on aldosterone's direct effects on cardiomyocyte electrical activity.
Purpose of the Study:
- To investigate the role of aldosterone in modulating whole-cell calcium current (I(Ca)) in adult rat ventricular myocytes.
- To elucidate the mechanisms underlying aldosterone's influence on cardiac electrophysiology.
Main Methods:
- Patch-clamp technique was employed to measure I(Ca) in isolated adult rat ventricular myocytes.
- Cells were treated with aldosterone (1 µmol/L) for varying durations (up to 24 hours).
- Effects were assessed in the presence of spironolactone, actinomycin D, and cycloheximide.
Main Results:
- Long-term (24 hours) aldosterone exposure significantly increased I(Ca) density.
- Short-term (≤6 hours) aldosterone exposure showed no significant effect on I(Ca).
- Spironolactone, actinomycin D, and cycloheximide blocked the aldosterone-induced increase in I(Ca) density.
Conclusions:
- Aldosterone exerts a long-latency, genomic effect on cardiomyocyte I(Ca) density, likely via increased channel expression.
- This aldosterone-mediated genomic action may contribute to the elevated I(Ca) observed during cardiac remodeling.
- Findings highlight a novel mechanism linking mineralocorticoid signaling to cardiac electrical remodeling.
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 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.