Rapid, nongenomic effects of aldosterone in the heart mediated by epsilon protein kinase C
| Autor: | Anastasia S. Mihailidou, Mahidi Mardini, John W. Funder |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Male
medicine.medical_specialty Patch-Clamp Techniques medicine.drug_class Sodium-Potassium-Chloride Symporters medicine.medical_treatment Heart Ventricles Protein Kinase C-epsilon Biology chemistry.chemical_compound Endocrinology Mineralocorticoid receptor Internal medicine medicine Animals Ventricular Function Patch clamp Enzyme Inhibitors Aldosterone Protein kinase C Protein Kinase C Muscle Cells Activator (genetics) Electric Conductivity Heart Steroid hormone chemistry Mineralocorticoid Rabbits Sodium-Potassium-Exchanging ATPase Intracellular |
| Zdroj: | Endocrinology. 145(2) |
| ISSN: | 0013-7227 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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