Electroneutral NaCl absorption in the proximal tubule: mechanisms of apical Na-coupled transport.

The proximal tubule utilizes multiple mechanisms to reabsorb filtered NaCl. In the early PCT electrogenic Na-coupled organic solute transport generates a lumen-negative PD which drives Cl- passively through the paracellular pathway. Preferential reabsorption of HCO3- and organic solutes in the early PCT elevates luminal Cl- concentration, which in the late PCT provides the driving force for passive reabsorption of both Na+ and Cl-. However, most of the NaCl reabsorbed in the PCT is mediated by an electroneutral mechanism in which equivalent amounts of Na+ and Cl- move transcellularly across apical and basolateral membranes. In the mammalian PCT the evidence overwhelmingly supports parallel Na+-H+ and Cl- -base exchangers as the mechanism by which Na+ and Cl- cross the apical membrane during electroneutral, transcellular NaCl reabsorption. OH-, HCO3-, formate and Ox- have all been suggested to be the anion exchanged for Cl-. An important physiologic contribution of formate has been shown in in vitro microperfusion studies [29]. Measurements of intracellular pH using fluorescent dyes [59, 60] support a quantitatively important role for formate and argue against a large contribution of OH- and HCO3-. The absence of a role for HCO3- is also supported by in vivo microperfusion studies using methoxazolamide [53]. The potential role of oxalate requires physiologic evaluation. To date, the experimental data suggest that Cl- -formate is probably the predominant anion exchange mechanism. One may ask why, in a process so critical as NaCl reabsorption, the tubule would choose to use a "toxin" rather than one of those ions more familiar to renal physiologists?(ABSTRACT TRUNCATED AT 250 WORDS)