Fig. 1: Basolateral AE4 of β-intercalated cells is not required for systemic sodium balance but for acid-base homeostasis.
a Representative confocal images of AE4 (light blue), AQP2 (red), and pendrin (green) in murine, porcine and human kidney demonstrating basal and lateral localization of AE4 in cortical pendrin-positive cells. b–d Ae4−/− and wild-type littermates (Ae4+/+) were challenged for 10 days with a salt-depleted diet. b Plasma volume measured by Evans blue dilution method, plasma renin activity and aldosterone concentration measured by ELISA (n = 8-11 animals per genotype, two-tailed Student’s t-test). c Representative immunoblots of total renal sodium chloride cotransporter NCC and phosphorylated (p)NCC protein levels, ponceau red staining indicates equal loading. Graphs exhibit densitometric quantification of protein levels normalized to ponceau red staining, relative levels to Ae4+/+ are plotted (n = 7 animals per genotype, two-tailed Student’s t-test). The effect of the NCC blocker hydrochlorothiazide (HCTZ, 10 mg/kg) on urinary Na+ was not different between both genotypes (n = 7–10 animals per genotype, ns: not significant p > 0.05, two-way ANOVA followed by Bonferroni’s multiple comparisons test). d AE4 deletion induces hypochloremic alkalosis during salt-depletion. Graphs exhibit blood pH, blood pCO2, plasma [HCO3−], and plasma [Cl−] (n = 18–26 animals per parameter and genotype, two-tailed Student’s t-test). e, f Ae4+/+ and Ae4−/− mice were alkali-loaded for 7 days under salt-depletion (low salt diet with 230 mM NaHCO3 added to the drinking water). Before the alkali-loading (day 0) mice received normal diet. Graphs show e blood pH, plasma [HCO3−], blood pCO2, and plasma [Cl−] and f plasma [K+] and [aldosterone] of Ae4+/+ and Ae4−/− littermates without and after 1, 2, and 7 days of alkali-loading (n = 6–17 animals per genotype and day of alkali-loading, two-way ANOVA followed by Bonferroni’s multiple comparisons test for Ae4+/+ vs Ae4−/−). All data are presented as mean ± SEM. In b–d each point or square denotes one animal. Source data are provided as a Source Data file.
