@article{21cab674fc3b4024a9e4285c4d7a0ddb,
title = "Potassium modulates electrolyte balance and blood pressure through effects on distal cell voltage and chloride",
abstract = "Dietary potassium deficiency, common in modern diets, raises blood pressure and enhances salt sensitivity. Potassium homeostasis requires a molecular switch in the distal convoluted tubule (DCT), which fails in familial hyperkalemic hypertension (pseudohypoaldosteronism type 2), activating the thiazide-sensitive NaCl cotransporter, NCC. Here, we show that dietary potassium deficiency activates NCC, even in the setting of high salt intake, thereby causing sodium retention and a rise in blood pressure. The effect is dependent on plasma potassium, which modulates DCT cell membrane voltage and, in turn, intracellular chloride. Low intracellular chloride stimulates WNK kinases to activate NCC, limiting potassium losses, even at the expense of increased blood pressure. These data show that DCT cells, like adrenal cells, sense potassium via membrane voltage. In the DCT, hyperpolarization activates NCC via WNK kinases, whereas in the adrenal gland, it inhibits aldosterone secretion. These effects work in concert to maintain potassium homeostasis.",
author = "Terker, {Andrew S.} and Chong Zhang and McCormick, {James A.} and Lazelle, {Rebecca A.} and Chengbiao Zhang and Meermeier, {Nicholas P.} and Siler, {Dominic A.} and Park, {Hae J.} and Yi Fu and Cohen, {David M.} and Weinstein, {Alan M.} and Wang, {Wen Hui} and Yang, {Chao Ling} and Ellison, {David H.}",
note = "Funding Information: This work was funded in part by grants from the NIH (DK51496 to D.H.E., DK54983 to W.-H.W., NIH DK-29857 to A.M.W., and DK098141 to J.A.M.) and the Department of Veterans Affairs (1I0BX002228-01A1 to D.H.E.). A.S.T. (3PRE14090030) and R.A.L. (14PRE18330021) were recipients of American Heart Association predoctoral fellowship awards. Chong Zhang was supported by the Shanghai Municipal Education Commission and a Shanghai Jiao Tong University K.C. Wong Medical Fellowship fund. This work was performed by A.S.T. in partial fulfillment for a PhD in Cell & Developmental Biology from Oregon Health and Science University. It was also supported by Shared Instrumentation Grant Number S10-RR023432 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. We wish to acknowledge Aurelie Snyder and the Advanced Light Microscopy Core at The Jungers Center, OHSU, for technical assistance. ",
year = "2015",
month = jan,
day = "6",
doi = "10.1016/j.cmet.2014.12.006",
language = "English (US)",
volume = "21",
pages = "39--50",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "1",
}