| First Author | Osis G | Year | 2019 |
| Journal | Am J Physiol Renal Physiol | PubMed ID | 31188034 |
| Mgi Jnum | J:284380 | Mgi Id | MGI:6380982 |
| Doi | 10.1152/ajprenal.00015.2019 | Citation | Osis G, et al. (2019) Regulation of Renal NaDC1 Expression and Citrate Excretion by NBCe1-A. Am J Physiol Renal Physiol |
| abstractText | Citrate is critical for acid-base homeostasis and to prevent calcium-nephrolithiasis. Both metabolic acidosis and hypokalemia decrease citrate excretion and increase expression of NaDC1 (SLC13A2), the primary protein involved in citrate reabsorption,. However, the mechanisms transducing extracellular signals and mediating these responses are incompletely understood. This study's purpose was to determine the role of the NBCe1 A variant (NBCe1-A) in citrate metabolism under basal conditions and in response to acid-loading and hypokalemia. NBCe1-A deletion increased citrate excretion and decreased NaDC1 expression in proximal convoluted tubule (PCT) and proximal straight tubule (PST) in medullary ray (PST-MR), but not in PST in outer medulla (PST-OM). Acid-loading wild-type (WT) mice decreased citrate excretion. NaDC1 expression increased only in PCT and PST-MR, and not in PST-MR. In NBCe1-A KO mice, the acid-loading change in citrate excretion was unaffected, changes in PCT NaDC1 expression were blocked, and there was an adaptive increase in PST-MR. Hypokalemia in WT mice decreased citrate excretion; NaDC1 expression increased only in PCT and PST-MR. NBCe1-A KO blocked both the citrate and NaDC1 changes. We conclude: (a) adaptive changes in NaDC1 expression in response to metabolic acidosis and hypokalemia occur specifically in PCT and PST-MR, i.e., in cortical proximal tubule segments; (b) NBCe1-A is necessary for normal basal, metabolic acidosis and hypokalemia-stimulated citrate metabolism, and does so by regulating NaDC1 expression in cortical proximal tubule segments; and, (c) adaptive increases in PST-OM NaDC1 expression occur in NBCe1-A KO mice in response to acid-loading that do not occur in WT mice. |
