Regulation of Renal NaDC1 Expression and Citrate Excretion by NBCe1-A.

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. PMID: 31188034 [PubMed - as supplied by publisher]
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research