The potassium channel, Kir3. 4 participates in angiotensin II-stimulated aldosterone production by a human adrenocortical cell line

K Oki, MW Plonczynski, ML Lam… - …, 2012 - academic.oup.com
K Oki, MW Plonczynski, ML Lam, EP Gomez-Sanchez, CE Gomez-Sanchez
Endocrinology, 2012academic.oup.com
Angiotensin II (A-II) regulation of aldosterone secretion is initiated by inducing cell
membrane depolarization, thereby increasing intracellular calcium and activating the
calcium calmodulin/calmodulin kinase cascade. Mutations in the selectivity filter of the
KCNJ5 gene coding for inward rectifying potassium channel (Kir) 3.4 has been found in
about one third of aldosterone-producing adenomas. These mutations result in loss of
selectivity of the inward rectifying current for potassium, which causes membrane …
Angiotensin II (A-II) regulation of aldosterone secretion is initiated by inducing cell membrane depolarization, thereby increasing intracellular calcium and activating the calcium calmodulin/calmodulin kinase cascade. Mutations in the selectivity filter of the KCNJ5 gene coding for inward rectifying potassium channel (Kir)3.4 has been found in about one third of aldosterone-producing adenomas. These mutations result in loss of selectivity of the inward rectifying current for potassium, which causes membrane depolarization and opening of calcium channels and activation of the calcium calmodulin/calmodulin kinase cascade and results in an increase in aldosterone secretion. In this study we show that A-II and a calcium ionophore down-regulate the expression of KCNJ5 mRNA and protein. Activation of Kir3.4 by naringin inhibits A-II-stimulated membrane voltage and aldosterone secretion. Overexpression of KCNJ5 in the HAC15 cells using a lentivirus resulted in a decrease in membrane voltage, intracellular calcium, expression of steroidogenic acute regulatory protein, 3-β-hydroxysteroid dehydrogenase 3B2, cytochrome P450 11B1 and cytochrome P450 11B2 mRNA, and aldosterone synthesis. In conclusion, A-II appears to stimulate aldosterone secretion by depolarizing the membrane acting in part through the regulation of the expression and activity of Kir3.4.
Oxford University Press