title: Regulation of aldosterone biosynthesis by the Kir3.4 (KCNJ5) potassium channel.
abstract: 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 KCNJ5, 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 KCNJ5 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 KCNJ5 induces cell proliferation and adenoma formation remains unclear.
authors.affiliation: Research and Endocrine Service, GV (Sonny) Montgomery VA Medical Center, University of Mississippi Medical Center, Jackson, MS, USA; Division of Endocrinology, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Carolina
authors.initials: C
authors.lastname: Velarde-Miranda
authors.forename: Elise P
authors.initials: EP
authors.lastname: Gomez-Sanchez
authors.forename: Celso E
authors.initials: CE
authors.lastname: Gomez-Sanchez
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000235:genetics / Q000378:metabolism; D018246:Adrenocortical Adenoma / Q000235:genetics / Q000378:metabolism; D000450:Aldosterone / Q000096:biosynthesis* / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D006973:Hypertension / Q000378:metabolism; D009154:Mutation; D011188:Potassium / Q000378:metabolism; D015384:Zona Glomerulosa / Q000187:drug effects / Q000378:metabolism*
chemical_list: D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C484274:KCNJ5 protein, human; D000804:Angiotensin II; D000450:Aldosterone; D011188:Potassium
keywords: KCNJ5; Kir3.4; alsdosterone; angiotensin II; intracellular calcium; potassium channel