Developmental changes in proximal tubule NaCl transport

The proximal tubule reabsorbs two thirds of the filtered NaCl in an isoosmotic fashion. In the adult proximal tubule, active NaCl transport is mediated by the parallel operation of Na⁺/H⁺ and Cl⁻/base exchangers, and a substantive amount of chloride transport occurs passively across the paracellular pathway. Studies in the neonatal proximal tubule have resulted in unexpected results. The isoform of the Na⁺/H⁺ exchanger mediating proximal tubule sodium absorption, NHE3, is virtually absent in the neonatal rat kidney. NHE8, an isoform of the Na⁺/H⁺ exchange, in low abundance on the apical membrane of the adult proximal tubule, is present in high abundance in the neonatal segment. Whereas chloride permeability is high in the adult, favoring passive paracellular chloride flux, the neonatal proximal tubule is virtually impermeable to chloride ions. This is again due to a developmental change in isoforms of proteins forming the tight junction. The permeability properties of epithelia are due to a family of tight junction proteins called claudins. Claudins 6 and 9 are expressed in the neonatal proximal tubule at a time when chloride permeability is low, but these claudin isoforms are virtually absent in the adult segment. The causes for these postnatal changes in proximal tubular transport and developmental isoform changes are also discussed in this review.