Rapid, Nongenomic Effects of Aldosterone in the Heart Mediated by ε Protein Kinase C

Anastasia S. Mihailidou*, Mahidi Mardini, John W. Funder

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

102 Citations (Scopus)


Aldosterone elevates Na+/K+/2Cl- cotransporter activity in rabbit cardiomyocytes within 15 min, an effect blocked by K-canrenoate and thus putatively mineralocorticoid receptor mediated. Increased cotransporter activity raises intracellular [Na+] sufficient to produce a secondary increase in Na+-K+ pump activity; when this increase in intracellular [Na+] is prevented, a rapid effect of aldosterone to lower pump activity is seen. Addition of transcription inhibitor actinomycin D did not change basal or aldosterone-induced lowered pump activity, indicating a direct, nongenomic action of aldosterone. We examined a possible role for protein kinase C (PKC) in the rapid nongenomic effects of aldosterone. Single ventricular myocytes and pipette solutions containing 10 mM intracellular [Na+] were used in patch clamp studies to measure Na+-K+ pump activity. Aldosterone lowered pump current, an effect abolished by ε PKC (εPKC) inhibition but neither αPKC nor scrambled εPKC; addition of εPKC activator peptide mimicked the rapid aldosterone effect. In rabbits chronically infused with aldosterone, the lowered pump current in cardiomyocytes was acutely (≥15 min) restored by εPKC inhibition. These studies show that rapid effects of aldosterone on Na+-K+ pump activity are nongenomic and specifically εPKC mediated; in addition, such effects may be prolonged (7 d) and long-lived (∼4 h isolated cardiomyocyte preparation time). The rapid, prolonged, long-lived effects can be rapidly (≥15 min) reversed by εPKC blockade, suggesting a hitherto unrecognized complexity of aldosterone action in the heart and perhaps by extension other tissues.

Original languageEnglish
Pages (from-to)773-780
Number of pages8
Issue number2
Publication statusPublished - Feb 2004
Externally publishedYes


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