Fig 17. Model of ion transport in hRPTCs with HNF4A binding to SCL4A5 promoter.

In a hRPTC containing the SNP rs7571842 in SCL4A5 the model changes to what is depicted in Fig 17. Increasing intracellular Na⁺ concentration with high extracellular Na⁺ concentration or monensin (9 o’clock) increases NBCe2 mRNA, protein, and activity, while only marginally attenuating the protein and activity of NBCe1 (2 o’clock) in hRPTCs with SNPs in NBCe2. This results in a net increase in Na⁺ transport into the basolateral space. PAT1 (7 o’clock) activity increases because of an increase in intracellular bicarbonate (7 o’clock). NHE3 (9 o’clock) activity also increases because the increase in NBCe2 activity increases intracellular H⁺ following the conversion of transported HCO₃^- to H₂CO₃ and its dissociation to H⁺ and HCO₃^- resulting in a further increase in sodium reabsorption. An increase in HNF4A binding to the rs7571842 SLC4A5 increases its expression.