PubMed 23318698

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Kir3.4

Title: New insights into aldosterone-producing adenomas and hereditary aldosteronism: mutations in the K+ channel KCNJ5.

Authors: Ute I Scholl, Richard P Lifton

Journal, date & volume: Curr. Opin. Nephrol. Hypertens., 2013 Mar , 22, 141-7

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Primary aldosteronism is a major cause of secondary hypertension worldwide. This review describes the recent studies that have provided dramatic new insight into the pathogenesis of aldosterone-producing adenomas (APAs) and inherited primary aldosteronism, revealing the role of mutations in the potassium channel KCNJ5 in these disorders.Either of two somatic gain-of-function mutations in the inward rectifier potassium channel KCNJ5 (Kir3.4) are present in approximately 40% of APAs. These tumor-causing mutations are heterozygous and alter the channel's selectivity filter. Mutant channels gain permeability to sodium, resulting in cellular depolarization and activation of voltage-gated calcium channels. The resulting calcium influx is sufficient to produce aldosterone secretion and cell proliferation, accounting for APA development. Germline KCNJ5 mutations also result in either of two autosomal-dominant syndromes featuring early-onset primary aldosteronism. Mutations identical or similar to those found in APAs result in massive bilateral adrenal hyperplasia. A different mutation at the same position produces a less severe syndrome without adrenal hyperplasia because this mutation results in Na-dependent cell lethality caused by a drastic increase in Na conductance.These findings provide fundamental insight into the pathogenesis of APAs and primary aldosteronism, and have implications for new diagnostic and therapeutic strategies.