Format

Send to

Choose Destination
Cell Metab. 2015 Jan 6;21(1):39-50. doi: 10.1016/j.cmet.2014.12.006.

Potassium modulates electrolyte balance and blood pressure through effects on distal cell voltage and chloride.

Author information

1
Division of Nephrology & Hypertension, Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
2
Division of Nephrology & Hypertension, Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA; Department of Nephrology, Xinhua Hostpital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.
3
Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA.
4
Department of Neurological Surgery, Oregon Health & Science University, Portland, OR 97239, USA.
5
Division of Nephrology & Hypertension, Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA; VA Portland Health Care System, Portland, OR 97239, USA.
6
Department of Physiology and Biophysics, Weil Medical College, New York, NY 10065, USA.
7
Division of Nephrology & Hypertension, Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA; VA Portland Health Care System, Portland, OR 97239, USA. Electronic address: ellisond@ohsu.edu.

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.

PMID:
25565204
PMCID:
PMC4332769
DOI:
10.1016/j.cmet.2014.12.006
[Indexed for MEDLINE]
Free PMC Article

Publication type, MeSH terms, Substances, Grant support

Publication type

MeSH terms

Substances

Grant support

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center