Referenced in: none

Automatically associated channels: Kir3.4

Title: K+ channel mutations in adrenal aldosterone-producing adenomas and hereditary hypertension.

Authors: Murim Choi, Ute I Scholl, Peng Yue, Peyman Bjorklund, Bixiao Zhao, Carol Nelson-Williams, Weizhen Ji, Yoonsang Cho, Aniruddh Patel, Clara J Men, Elias Lolis, Max V Wisgerhof, David S Geller, Shrikant Mane, Per Hellman, Gunnar Westin, Göran Åkerström, Wenhui Wang, Tobias Carling, Richard P Lifton

Journal, date & volume: Science, 2011 Feb 11 , 331, 768-72

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/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.