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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 39-50 |
| Number of pages | 12 |
| Journal | Cell Metabolism |
| Volume | 21 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 6 2015 |
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ASJC Scopus subject areas
- Cell Biology
- Molecular Biology
- Physiology
Cite this
Potassium modulates electrolyte balance and blood pressure through effects on distal cell voltage and chloride. / Terker, Andrew S.; Zhang, Chong; McCormick, James (Jim); Lazelle, Rebecca A.; Zhang, Chengbiao; Meermeier, Nicholas P.; Siler, Dominic A.; Park, Hae J.; Fu, Yi; Cohen, David; Weinstein, Alan M.; Wang, Wen Hui; Yang, Chao-Ling; Ellison, David.
In: Cell Metabolism, Vol. 21, No. 1, 06.01.2015, p. 39-50.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Potassium modulates electrolyte balance and blood pressure through effects on distal cell voltage and chloride
AU - Terker, Andrew S.
AU - Zhang, Chong
AU - McCormick, James (Jim)
AU - Lazelle, Rebecca A.
AU - Zhang, Chengbiao
AU - Meermeier, Nicholas P.
AU - Siler, Dominic A.
AU - Park, Hae J.
AU - Fu, Yi
AU - Cohen, David
AU - Weinstein, Alan M.
AU - Wang, Wen Hui
AU - Yang, Chao-Ling
AU - Ellison, David
PY - 2015/1/6
Y1 - 2015/1/6
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84920607517&partnerID=8YFLogxK
U2 - 10.1016/j.cmet.2014.12.006
DO - 10.1016/j.cmet.2014.12.006
M3 - Article
C2 - 25565204
AN - SCOPUS:84920607517
VL - 21
SP - 39
EP - 50
JO - Cell Metabolism
JF - Cell Metabolism
SN - 1550-4131
IS - 1
ER -