| First Author | Zhang Y | Year | 2024 |
| Journal | Nat Commun | Volume | 15 |
| Issue | 1 | Pages | 5144 |
| PubMed ID | 38886379 | Mgi Jnum | J:358265 |
| Mgi Id | MGI:7659984 | Doi | 10.1038/s41467-024-49562-w |
| Citation | Zhang Y, et al. (2024) Low potassium activation of proximal mTOR/AKT signaling is mediated by Kir4.2. Nat Commun 15(1):5144 |
| abstractText | The renal epithelium is sensitive to changes in blood potassium (K(+)). We identify the basolateral K(+) channel, Kir4.2, as a mediator of the proximal tubule response to K(+) deficiency. Mice lacking Kir4.2 have a compensated baseline phenotype whereby they increase their distal transport burden to maintain homeostasis. Upon dietary K(+) depletion, knockout animals decompensate as evidenced by increased urinary K(+) excretion and development of a proximal renal tubular acidosis. Potassium wasting is not proximal in origin but is caused by higher ENaC activity and depends upon increased distal sodium delivery. Three-dimensional imaging reveals Kir4.2 knockouts fail to undergo proximal tubule expansion, while the distal convoluted tubule response is exaggerated. AKT signaling mediates the dietary K(+) response, which is blunted in Kir4.2 knockouts. Lastly, we demonstrate in isolated tubules that AKT phosphorylation in response to low K(+) depends upon mTORC2 activation by secondary changes in Cl(-) transport. Data support a proximal role for cell Cl(-) which, as it does along the distal nephron, responds to K(+) changes to activate kinase signaling. |
