Heterogeneity of chloride/base exchange in rabbit superficial and juxtamedullary proximal convoluted tubules

Active transcellular NaCl transport in the proximal convoluted tubule (PCT) is via apical parallel Na/H and Cl/base exchange. The mechanism of Cl/base exchange remains unclear. The present in vitro microperfusion study examined the mechanism of Cl/base exchange in superficial and juxtamedullary PCT by examining the rate of change in intracellular pH in response to luminal Cl removal. In superficial PCT the rate of Cl/base exchange was 24.0 ± 2.3 without formate, 36.4 ± 6.6 with 10 μM formate (P < 0.05), and 43.6 ± 2.8 pmol·mm^-1·min^-1 (P < 0.001) with 1 mM luminal formate. Cl/base exchange was inhibited by luminal 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS) in the presence and absence of formate. In juxtamedullary PCT, Cl/base exchange was 22.2 ± 3.8 without formate and 25.0 ± 5.4 pmol·mm^-1·min^-1 in the presence of 1 mM luminal formate [P = not significant (NS)]. Cl/base exchange was inhibited by luminal DIDS in juxtamedullary PCT. The rates of Cl/base exchange in both superficial and juxtamedullary PCT were not affected by 0.1 mM acetazolamide and 2 mM cyanide and were the same in the presence and absence of HCO₃/CO₂, consistent with Cl/OH rather than Cl/HCO₃ exchange. To examine the effect of formate on PCT transport, tubules were perfused with a high-Cl solution without organics simulating late proximal tubular fluid. In superficial PCT net volume absorption (J_V) was 0.00 ± 0.05 in the absence of formate and 0.14 ± 0.06 nl·mm^-1·min^-1 in the presence of 1 mM formate (P < 0.05). In juxtamedullary PCT J_V was 0.20 ± 0.08 in the absence of formate and 0.17 ± 0.07 nl·mm^-1·min^-1 in the presence of 1 mM formate (P = NS). In conclusion, superficial PCT have both a Cl/OH and Cl/formate exchanger. Cl/ formate exchange is present with physiological concentrations of formate. Addition of 1 mM formate stimulates Cl transport in superficial PCT. Juxtamedullary PCT have Cl/OH exchange but do not have Cl/formate exchange. Juxtamedullary PCT have Cl transport in the absence of formate, and the rate is not affected by formate.