| First Author | Al-Qusairi L | Year | 2023 |
| Journal | Am J Physiol Renal Physiol | Volume | 325 |
| Issue | 3 | Pages | F377-F393 |
| PubMed ID | 37498547 | Mgi Jnum | J:358383 |
| Mgi Id | MGI:7780222 | Doi | 10.1152/ajprenal.00193.2023 |
| Citation | Al-Qusairi L, et al. (2023) Dietary anions control potassium excretion: it is more than a poorly absorbable anion effect. Am J Physiol Renal Physiol 325(3):F377-F393 |
| abstractText | The urinary potassium (K(+)) excretion machinery is upregulated with increasing dietary K(+), but the role of accompanying dietary anions remains inadequately characterized. Poorly absorbable anions, including [Formula: see text], are thought to increase K(+) secretion through a transepithelial voltage effect. Here, we tested if they also influence the K(+) secretion machinery. Wild-type mice, aldosterone synthase (AS) knockout (KO) mice, or pendrin KO mice were randomized to control, high-KCl, or high-KHCO(3) diets. The K(+) secretory capacity was assessed in balance experiments. Protein abundance, modification, and localization of K(+)-secretory transporters were evaluated by Western blot analysis and confocal microscopy. Feeding the high-KHCO(3) diet increased urinary K(+) excretion and the transtubular K(+) gradient significantly more than the high-KCl diet, coincident with more pronounced upregulation of epithelial Na+ channels (ENaC) and renal outer medullary K(+) (ROMK) channels and apical localization in the distal nephron. Experiments in AS KO mice revealed that the enhanced effects of [Formula: see text] were aldosterone independent. The high-KHCO(3) diet also uniquely increased the large-conductance Ca(2+)-activated K(+) (BK) channel beta(4)-subunit, stabilizing BKalpha on the apical membrane, the Cl(-)/[Formula: see text] exchanger, pendrin, and the apical KCl cotransporter (KCC3a), all of which are expressed specifically in pendrin-positive intercalated cells. Experiments in pendrin KO mice revealed that pendrin was required to increase K(+) excretion with the high-KHCO(3) diet. In summary, [Formula: see text] stimulates K(+) excretion beyond a poorly absorbable anion effect, upregulating ENaC and ROMK in principal cells and BK, pendrin, and KCC3a in pendrin-positive intercalated cells. The adaptive mechanism prevents hyperkalemia and alkalosis with the consumption of alkaline ash-rich diets but may drive K(+) wasting and hypokalemia in alkalosis.NEW & NOTEWORTHY Dietary anions profoundly impact K(+) homeostasis. Here, we found that a K(+)-rich diet, containing [Formula: see text] as the counteranion, enhances the electrogenic K(+) excretory machinery, epithelial Na(+) channels, and renal outer medullary K(+) channels, much more than a high-KCl diet. It also uniquely induces KCC3a and pendrin, in B-intercalated cells, providing an electroneutral KHCO(3) secretion pathway. These findings reveal new K(+) balance mechanisms that drive adaption to alkaline and K(+)-rich foods, which should guide new treatment strategies for K(+) disorders. |
