| First Author | Chan CH | Year | 2021 |
| Journal | Int J Mol Sci | Volume | 22 |
| Issue | 3 | PubMed ID | 33498219 |
| Mgi Jnum | J:303924 | Mgi Id | MGI:6693894 |
| Doi | 10.3390/ijms22030999 | Citation | Chan CH, et al. (2021) MST3 Involvement in Na(+) and K(+) Homeostasis with Increasing Dietary Potassium Intake. Int J Mol Sci 22(3) |
| abstractText | 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. |
