| First Author | Ferdaus MZ | Year | 2023 |
| Journal | Am J Physiol Cell Physiol | Volume | 324 |
| Issue | 5 | Pages | C1171-C1178 |
| PubMed ID | 37036298 | Mgi Jnum | J:358275 |
| Mgi Id | MGI:7471271 | Doi | 10.1152/ajpcell.00094.2023 |
| Citation | Ferdaus M, et al. (2023) Bicarbonate is the primary inducer of KCC3a expression in renal cortical B-type intercalated cells. Am J Physiol Cell Physiol |
| abstractText | A primary function of intercalated cells in the distal tubule of the kidney is to maintain pH homeostasis. For example, type B intercalated cells secrete bicarbonate largely through the action of the apical Cl(-)/HCO(3)(-) exchanger, pendrin, which helps correct metabolic alkalosis. Since both the K-Cl cotransporter, KCC3a, and pendrin colocalize to the apical region of type B and non-A, non-B intercalated cells and since both are upregulated in models of metabolic alkalosis, such as with dietary NaHCO(3) loading, we raised the possibility that apical KCC3a facilitates pendrin-mediated bicarbonate secretion, such as through apical Cl(-) recycling. The purpose of this study was to determine if KCC3a abundance changes through intake of bicarbonate alone or through bicarbonate plus its accompanying cation, and if it requires a direct interaction with pendrin or the renin-angiotensin-aldosterone system. We observed that KCC3a protein abundance, but not mRNA, increases in a mouse model of metabolic alkalosis, achieved with dietary NaHCO(3) or KHCO(3) intake. Bicarbonate ion increases KCC3a abundance, both in vivo and in vitro, independently of the accompanying cation. Moreover, bicarbonate intake upregulates KCC3a independently of aldosterone or angiotensin II. Since NaHCO(3) intake increased KCC3a abundance in wild type as well as in pendrin knockout mice, this KCC3a upregulation by bicarbonate does not depend on a direct interaction with pendrin. We conclude that increased extracellular bicarbonate, as observed in models of metabolic alkalosis, directly raises KCC3a abundance independently of angiotensin II, aldosterone, or changes in KCC3a transcription and does not involve a direct interaction with pendrin. |
