TASK1 and TASK3 potassium channels: determinants of aldosterone secretion and adrenocortical zonation.
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 2-P-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.
Bandulik
S
S
Physiology, University of Regensburg, Regensburg, Germany.
Penton
D
D
Barhanin
J
J
Warth
R
R
D000302:Adrenal Cortex / Q000378:metabolism*; D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009928:Organ Specificity; D015221:Potassium Channels / Q000502:physiology; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014018:Tissue Distribution
C498655:KCNK9 protein, human; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; C420132:potassium channel subfamily K member 3; D000450:Aldosterone