| First Author | Terker AS | Year | 2022 |
| Journal | Cell Rep | Volume | 41 |
| Issue | 12 | Pages | 111840 |
| PubMed ID | 36543132 | Mgi Jnum | J:358264 |
| Mgi Id | MGI:7424687 | Doi | 10.1016/j.celrep.2022.111840 |
| Citation | Terker AS, et al. (2022) Kir4.2 mediates proximal potassium effects on glutaminase activity and kidney injury. Cell Rep 41(12):111840 |
| abstractText | Inadequate potassium (K(+)) consumption correlates with increased mortality and poor cardiovascular outcomes. Potassium effects on blood pressure have been described previously; however, whether or not low K(+) independently affects kidney disease progression remains unclear. Here, we demonstrate that dietary K(+) deficiency causes direct kidney injury. Effects depend on reduced blood K(+) and are kidney specific. In response to reduced K(+), the channel Kir4.2 mediates altered proximal tubule (PT) basolateral K(+) flux, causing intracellular acidosis and activation of the enzyme glutaminase and the ammoniagenesis pathway. Deletion of either Kir4.2 or glutaminase protects from low-K(+) injury. Reduced K(+) also mediates injury and fibrosis in a model of aldosteronism. These results demonstrate that the PT epithelium, like the distal nephron, is K(+) sensitive, with reduced blood K(+) causing direct PT injury. Kir4.2 and glutaminase are essential mediators of this injury process, and we identify their potential for future targeting in the treatment of chronic kidney disease. |
