K+ Channel Mutations in Adrenal Aldosterone-Producing Adenomas and Hereditary Hypertension
By Murim Choi, U. Scholl, Peng Yue, P. Björklund, Bixiao Zhao, C. Nelson-Williams, W. Ji, Yoonsang Cho, A. Patel, C. Men and 10 more. Science, 2011
959 citations recorded by the source corpus.
Potassium channel mutations drive both cell growth and hormone production in an adrenal tumor that causes severe hypertension. 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.
Subfields: Endocrinology, Diabetes and Metabolism, Molecular Biology, Surgery
View Paper: https://www.semanticscholar.org/paper/c645ff58c98f07589d07eca23c5c81c27d62d0e4
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Citations in the corpus
- Co-occurring genomic alterations define major subsets of KRAS - mutant lung adenocarcinoma with distinct biology, immune profiles, and therapeutic vulnerabilities (2015, neutral): “Sample preparation, basic alignment and downstream analyses were performed according to previously described methods (53-55).”
- Plant- and Seaweed-Based Extracts Increase Yield but Differentially Modulate Nutritional Quality of Greenhouse Spinach through Biostimulant Action (2018, background): “The lowest ratio observed in treated spinach is important from a nutritional point of view, as diets with low Na/K ratio are correlated with lower incidence of heart attacks and hypertension [46].”
- Hypertension Renin–Angiotensin–Aldosterone System Alterations (2015, background): “4.(112) This mutation results in the loss of K-selectivity and increased Na conductance, leading to”
- The Physiology, Pathology, and Pharmacology of Voltage-Gated Calcium Channels and Their Future Therapeutic Potential (2015, background): “This also includesmutations in GIRK4K+ channels (KCNJ5) (Choi et al., 2011) and in the Na+/K+-ATPase (ATP1A1) (Azizan et al., 2013; Beuschlein et al., 2013).”