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Regulation of aldosterone biosynthesis by the K ir3.4 ( KCNJ 5) potassium channel
Author(s) -
VelardeMiranda Carolina,
GomezSanchez Elise P,
GomezSanchez Celso E
Publication year - 2013
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12151
Subject(s) - aldosterone , zona glomerulosa , depolarization , medicine , endocrinology , chemistry , microbiology and biotechnology , potassium channel , biology , angiotensin ii , blood pressure
Summary The G ‐protein‐activated inwardly rectifying potassium channel Kir3.4 is expressed in the zona glomerulosa cell membrane and transports potassium out of the cell. Angiotensin II stimulation of aldosterone secretion is mediated, in part, by suppression of the transcription of KCNJ 5, the gene coding for Kir3.4, and blocking channel activity. This results in membrane depolarization, mobilization of intracellular calcium, activation of the calcium–calmodulin pathway and increasing gene transcription of steroidogenic enzymes required for aldosterone secretion. In 40–60% of aldosterone‐producing adenomas there is a somatic mutation in the region of the KCNJ 5 gene that codes for the selectivity filter that decreases potassium selectivity, allowing sodium to leak into the cells, thus depolarizing the membrane and initiating events that result in increased aldosterone synthesis. The mechanism by which mutated KCNJ 5 induces cell proliferation and adenoma formation remains unclear.