Objective: 

Claudin-16 is defective in familial hypomagnesemia with hypercalciuria and nephrocalcinosis. Claudin-16 knockdown mice (KD) show reduced cation selectivity in the thick ascending limb and a disturbed electrolyte homeostasis. In addition acid/base balance was affected. Although blood pH was completely compensated in half year old mice, KD blood showed significantly higher HCO₃^- concentrations compared with wild type mice (WT). Urine H⁺ concentration was sixfold higher and the urine HCO₃^- concentration was reduced by more than fivefold in KD. We now investigate the expression pattern of proteins involved in acid-base transport along the nephron of 1.5-years old KD and their respective WT litter-mates.

Methods: 

We did immunofluorescence (IF) staining of freshly isolated cortical collecting ducts for the acid-base transporters V-type H⁺-ATPase, AE1 and Pendrin as well as for AQP2 and bENaC. The expression pattern was analyzed using laser scanning microscopy and the ratio of the IF intensity representing the plasma membrane and intracellular staining was calculated as a measure of membrane expression.

Results: 

In KD type B intercalated cells 44% of H⁺-ATPase IF intensity was localized in the basolateral membrane compared to 21% in WT. In addition the luminal membrane expression of Pendrin was increased in KD with 25% compared to 14%, respectively. We did not find any difference in the distribution of the IF signal across the cells for AQP2, bENaC and AE1.

Conclusion: 

The present data suggest that the acid excretion phenotype in KD induces compensatory activation of type B intercalated cells in cortical collecting ducts.