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K+ Channel Mutation...
K+ Channel Mutations in Adrenal Aldosterone-Producing Adenomas and Hereditary Hypertension
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Choi, Murim (author)
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Scholl, Ute I. (author)
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Yue, Peng (author)
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- Björklund, Peyman (author)
- Uppsala universitet,Institutionen för kirurgiska vetenskaper
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Zhao, Bixiao (author)
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Nelson-Williams, Carol (author)
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Ji, Weizhen (author)
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Cho, Yoonsang (author)
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Patel, Aniruddh (author)
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Men, Clara J. (author)
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Lolis, Elias (author)
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Wisgerhof, Max V. (author)
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Geller, David S. (author)
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Mane, Shrikant (author)
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- Hellman, Per (author)
- Uppsala universitet,Institutionen för kirurgiska vetenskaper,Endokrinkirurgi, Endocrine Surgery
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- Westin, Gunnar (author)
- Uppsala universitet,Institutionen för kirurgiska vetenskaper,Endokrinkirurgi, Endocrine Surgery
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- Åkerström, Göran (author)
- Uppsala universitet,Institutionen för kirurgiska vetenskaper,Endokrinkirurgi, Endocrine Surgery
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Wang, Wenhui (author)
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Carling, Tobias (author)
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Lifton, Richard P. (author)
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(creator_code:org_t)
- American Association for the Advancement of Science (AAAS), 2011
- 2011
- English.
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 331:6018, s. 768-772
- Related links:
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http://circres.ahajo...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- 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.
Keyword
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Choi, Murim
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Scholl, Ute I.
-
Yue, Peng
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Björklund, Peyma ...
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Zhao, Bixiao
-
Nelson-Williams, ...
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show more...
-
Ji, Weizhen
-
Cho, Yoonsang
-
Patel, Aniruddh
-
Men, Clara J.
-
Lolis, Elias
-
Wisgerhof, Max V ...
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Geller, David S.
-
Mane, Shrikant
-
Hellman, Per
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Westin, Gunnar
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Åkerström, Göran
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Wang, Wenhui
-
Carling, Tobias
-
Lifton, Richard ...
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show less...
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Science
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Uppsala University