Developmental regulation of chloride/formate exchange in guinea pig proximal tubules

Abstract

There is a marked decrease in renal NaCl excretion immediately following birth. To test the hypothesis that parallel upregulation of the proximal tubule apical membrane Na+/H+ and Cl-/formate exchangers contributes to this postnatal adaptation, we measured exchanger activities in brush-border membrane vesicles from near-term fetal, 3- to 5-day-old, and adult guinea pigs. Uptake of 36Cl- was measured in the presence of an outwardly directed formate gradient and an inwardly directed proton gradient. In other experiments, 22Na+ uptake was measured in the presence of an outwardly directed proton gradient. 36Cl- uptake was inhibitable by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and furosemide, and 22Na+ uptake was inhibitable by amiloride. Maximal uptakes of both 36Cl- and 22Na+ exceeded 2-h equilibration values in vesicles from newborn and adult guinea pigs, suggesting transporter-mediated uptake. Such overshoots were not seen with the vesicles from fetuses. Compared with vesicles from fetuses, the initial velocity of formate-driven 36Cl- uptake was 73% greater in vesicles from newborns and 65% greater in vesicles from adults. These results demonstrate parallel upregulation of proximal tubule Na+/H+ and Cl-/formate exchanger activities immediately after birth. This parallel upregulation may be important in mediating the postnatal decrease in renal NaCl excretion.