Role of Na+-H+ antiport in rat proximal tubule NaCl absorption.

We recently showed that, in the presence of physiological sodium concentrations, 4.3 mM luminal amiloride inhibits 90% of apical membrane Na+-H+ antiporter activity in the in vivo microperfused rat proximal convoluted tubule. In the present studies we examined the effect of 4.3 mM luminal amiloride on transepithelial NaCl absorption from a high-chloride, low-bicarbonate perfusate, simulating the tubular fluid of the late proximal tubule. Both chloride and volume absorption were inhibited approximately 44%, consistent with inhibition of most of transcellular NaCl absorption, and suggestive of parallel Na+-H+ and Cl(-)-base exchange as the mechanism of NaCl uptake across the apical membrane. Methazolamide (10(-4) M), a potent inhibitor of renal carbonic anhydrase, had no significant effect on either volume or chloride absorption, suggesting that a carbonic anhydrase-independent mechanism is at least partially involved in chloride absorption. Hydrochlorothiazide (1 mM), an inhibitor of electroneutral NaCl cotransport in tight epithelia, did not significantly affect either volume or chloride absorption. Thus these studies suggest that, in the rat, the mechanism of apical membrane electroneutral NaCl uptake is Na+-H+ and Cl- -base exchange.