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K+ Channel Mutations in Adrenal Aldosterone-Producing Adenomas and Hereditary Hypertension
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
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2011 (English)In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 331, no 6018, 768-772 p.Article in journal (Refereed) Published
Abstract [en]

Endocrine tumors such as aldosterone-producing adrenal adenomas (APAs), a cause of severe hypertension, feature constitutive hormone production and unrestrained cell proliferation; the mechanisms linking these events are unknown. We identify two recurrent somatic mutations in and near the selectivity filter of the potassium (K+) channel KCNJ5 that are present in 8 of 22 human APAs studied. Both produce increased sodium (Na+) conductance and cell depolarization, which in adrenal glomerulosa cells produces calcium (Ca2+) entry, the signal for aldosterone production and cell proliferation. Similarly, we identify an inherited KCNJ5 mutation that produces increased Na+ conductance in a Mendelian form of severe aldosteronism and massive bilateral adrenal hyperplasia. These findings explain pathogenesis in a subset of patients with severe hypertension and implicate loss of K+ channel selectivity in constitutive cell proliferation and hormone production.

Place, publisher, year, edition, pages
2011. Vol. 331, no 6018, 768-772 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-149566DOI: 10.1126/science.1198785ISI: 000287205700070PubMedID: 21311022OAI: oai:DiVA.org:uu-149566DiVA: diva2:405193
Available from: 2011-03-21 Created: 2011-03-21 Last updated: 2016-04-28

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Björklund, PeymanHellman, PerWestin, GunnarÅkerström, Göran
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