K+ channel mutations in adrenal aldosterone-producing adenomas and hereditary hypertension.
Science
; 331(6018): 768-72, 2011 Feb 11.
Article
em En
| MEDLINE
| ID: mdl-21311022
ABSTRACT
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 (Ca(2+)) 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias do Córtex Suprarrenal
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Adenoma Adrenocortical
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Aldosterona
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Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G
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Hiperaldosteronismo
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Hipertensão
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Mutação
Tipo de estudo:
Prognostic_studies
Limite:
Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article