Inhibition of Low Threshold Calcium Channels by Angiotensin II in Adrenal Glomerulosa Cells through Activation of Protein Kinase C (∗)

In adrenal glomerulosa cells, low threshold voltage-activated (T-type) calcium channels play a crucial role in coupling physiological variations of extracellular potassium to aldosterone biosynthesis. Angiotensin II markedly reduced the activity of these channels by shifting their activation curve t...

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Bibliographic Details
Published in:The Journal of biological chemistry 1995-06, Vol.270 (25), p.15137-15142
Main Authors: Rossier, Michel F., Aptel, Hervé B.C., Python, Christophe P., Burnay, Muriel M., Vallotton, Michel B., Capponi, Alessandro M.
Format: Article
Language:English
Subjects:
Aldosterone - metabolism
Angiotensin II - pharmacology
Animals
Calcium - metabolism
Calcium Channel Blockers - pharmacology
Calcium Channels - physiology
Cattle
Cells, Cultured
Cytosol - metabolism
Diglycerides - pharmacology
Drug Interactions
Enzyme Activation
Kinetics
Membrane Potentials - drug effects
Membrane Potentials - physiology
Patch-Clamp Techniques
Potassium - pharmacology
Protein Kinase C - metabolism
Tetradecanoylphorbol Acetate - pharmacology
Zona Glomerulosa - drug effects
Zona Glomerulosa - physiology
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Summary:In adrenal glomerulosa cells, low threshold voltage-activated (T-type) calcium channels play a crucial role in coupling physiological variations of extracellular potassium to aldosterone biosynthesis. Angiotensin II markedly reduced the activity of these channels by shifting their activation curve toward positive voltage values. This inhibition of the channels resulted in a marked decrease of the cytosolic free calcium concentration maintained by potassium. This effect was abolished by losartan, a specific antagonist of the angiotensin II AT1 receptor. Hormone action on T-type channels appeared to be mediated by protein kinase C because 1) it was mimicked by phorbol ester and diacylglycerol, and 2) it was significantly reduced by decreasing protein kinase C activity with specific inhibitors such as chelerythrine chloride or a pseudosubstrate of the enzyme, as well as by protein kinase C down-regulation. Similarly, protein kinase C activation reduced the cytosolic calcium response to potassium and the steroidogenic action of this agonist. Low threshold T-type calcium channels therefore appear as potential sites for the modulation of steroidogenesis by protein kinase C in adrenal glomerulosa cells.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.270.25.15137