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Article

MST3 Involvement in Na+ and K+ Homeostasis with Increasing Dietary Potassium Intake

1
Department of Nephrology, Chang Bing Show Chwan Memorial Hospital, Lukang, Changhua 505, Taiwan
2
Department of Physiology, National Cheng Kung University Medical College, Tainan 70101, Taiwan
3
School of Pharmacy, China Medical University, Taichung 406040, Taiwan
4
Department of Nursing, Asia University, Taichung 41354, Taiwan
5
Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 406040, Taiwan
*
Author to whom correspondence should be addressed.
Academic Editor: Pasquale Strazzullo
Int. J. Mol. Sci. 2021, 22(3), 999; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22030999
Received: 15 December 2020 / Revised: 14 January 2021 / Accepted: 15 January 2021 / Published: 20 January 2021
(This article belongs to the Special Issue Sodium Intake and Related Diseases)
K+ loading inhibits NKCC2 (Na-K-Cl cotransporter) and NCC (Na-Cl cotransporter) in the early distal tubules, resulting in Na+ delivery to the late distal convoluted tubules (DCTs). In the DCTs, Na+ entry through ENaC (epithelial Na channel) drives K+ secretion through ROMK (renal outer medullary potassium channel). WNK4 (with-no-lysine 4) regulates the NCC/NKCC2 through SAPK (Ste20-related proline-alanine-rich kinase)/OSR1 (oxidative stress responsive). K+ loading increases intracellular Cl, which binds to the WNK4, thereby inhibiting autophosphorylation and downstream signals. Acute K+ loading-deactivated NCC was not observed in Cl-insensitive WNK4 mice, indicating that WNK4 was involved in K+ loading-inhibited NCC activity. However, chronic K+ loading deactivated NCC in Cl-insensitive WNK4 mice, indicating that other mechanisms may be involved. We previously reported that mammalian Ste20-like protein kinase 3 (MST3/STK24) was expressed mainly in the medullary TAL (thick ascending tubule) and at lower levels in the DCTs. MST3−/− mice exhibited higher ENaC activity, causing hypernatremia and hypertension. To investigate MST3 function in maintaining Na+/K+ homeostasis in kidneys, mice were fed diets containing various concentrations of Na+ and K+. The 2% KCl diets induced less MST3 expression in MST3−/− mice than that in wild-type (WT) mice. The MST3−/− mice had higher WNK4, NKCC2-S130 phosphorylation, and ENaC expression, resulting in lower urinary Na+ and K+ excretion than those of WT mice. Lower urinary Na+ excretion was associated with elevated plasma [Na+] and hypertension. These results suggest that MST3 maintains Na+/K+ homeostasis in response to K+ loading by regulation of WNK4 expression and NKCC2 and ENaC activity. View Full-Text
Keywords: MST3; STK24; high potassium; ENaC; NKCC2; SPAK; OSR1; WNK4 MST3; STK24; high potassium; ENaC; NKCC2; SPAK; OSR1; WNK4
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MDPI and ACS Style

Chan, C.-H.; Wu, S.-N.; Bao, B.-Y.; Li, H.-W.; Lu, T.-L. MST3 Involvement in Na+ and K+ Homeostasis with Increasing Dietary Potassium Intake. Int. J. Mol. Sci. 2021, 22, 999. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22030999

AMA Style

Chan C-H, Wu S-N, Bao B-Y, Li H-W, Lu T-L. MST3 Involvement in Na+ and K+ Homeostasis with Increasing Dietary Potassium Intake. International Journal of Molecular Sciences. 2021; 22(3):999. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22030999

Chicago/Turabian Style

Chan, Chee-Hong, Sheng-Nan Wu, Bo-Ying Bao, Houng-Wei Li, and Te-Ling Lu. 2021. "MST3 Involvement in Na+ and K+ Homeostasis with Increasing Dietary Potassium Intake" International Journal of Molecular Sciences 22, no. 3: 999. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22030999

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