TASK1 and TASK3 Potassium Channels: Determinants of Aldosterone Secretion and Adrenocortical Zonation

被引:40
作者
Bandulik, S. [1 ]
Penton, D. [1 ]
Barhanin, J. [2 ,3 ]
Warth, R. [1 ]
机构
[1] Univ Regensburg, Regensburg, Germany
[2] CNRS, Transport Ionique Aspects Normaux & Pathol, F-06034 Nice, France
[3] Univ Nice Sophia Antipolis, Nice, France
关键词
K2P; KCNK2; KCNK3; KCNK9; adrenocortical zonation; aldosterone; angiotensin II; adrenal cortex; BACKGROUND K+ CHANNEL; ANGIOTENSIN-II; GLOMERULOSA CELLS; MEMBRANE DEPOLARIZATION; SUBUNIT COMPOSITION; IONIC CURRENTS; ADRENAL-CORTEX; MESSENGER-RNA; CONDUCTANCE; EXPRESSION;
D O I
10.1055/s-0029-1243601
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Potassium channels control the membrane voltage of aldosterone-producing zona glomerulosa cells. They are responsible for the unique K+ sensitivity of these cells and are important molecular targets of angiotensin II signaling. Among the 78 pore-forming K+ channels in human genome only a few are found in adrenal glands. The 2P-domain K+ channels TASK1 and TASK3 are strongly expressed in the adrenal cortex and produce a background K+ conductance, which is pivotal for the regulation of the aldosterone secretion in zona glomerulosa cells. Disruption of the TASK1 gene in mice resulted in an autonomous aldosterone production and caused a remarkable aberrant expression of aldosterone synthase in zona fasciculata cells that normally produce glucocorticoids. After puberty, only in male mice aldosterone production was switched off in the zona fasciculata and regular zonation of aldosterone synthase occurred. In double mutant TASK1(-/-)/TASK3(-/-) mice, also adult male mice displayed primary hyperaldosteronism. Therefore, these knockout mice are interesting models to study mechanisms of autonomous aldosterone production and adrenocortical zonation. These data suggest that modifications of the adrenocortical K+ conductances could also contribute to autonomic aldosterone production and primary hyperaldosteronism in humans.
引用
收藏
页码:450 / 457
页数:8
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