Proximal bicarbonate absorption independent of Na+-H+ exchange: effect of bicarbonate load

Abstract

To study proximal tubule bicarbonate absorption that is not due to the neutral Na+-H+ antiporter, mid to late proximal convolutions of the rat kidney were microperfused in vivo with a sodium-free choline solution containing 10(-3) M amiloride. The average sodium concentration resulting from sodium influx was 12 mM. At such low intraluminal [Na+], 10(-3) M amiloride should have inhibited the Na+-H+ antiporter by greater than 95%. When 25 mM HCO3- was in the perfusion fluid, measured total CO2 absorption was 100 pmol.mm-1.min-1. When luminal [HCO3-] was raised to 50 mM, and blood [HCO3-] was also raised to approximately 50 mM to avoid a transepithelial HCO3- concentration gradient, total CO2 absorption increased to greater than 300 pmol.mm-1.min-1. Thus raising intraluminal HCO3- concentration caused a marked increase in total CO2 absorption even though intraluminal [Na+] was low and amiloride was present. Control perfusions containing 140 mM Na+ yielded total CO2 absorption that was approximately 100 pmol.mm-1.min-1 higher than with the respective sodium-free perfusion solutions. In additional experiments, either DCCD or NEM was added to sodium-free perfusion solutions to inhibit H+-ATPase. These inhibitors reduced Na+-H+ independent total CO2 absorption markedly. Our observations suggest that under physiological acid-base conditions, sodium-independent H+ secretion can account for approximately 50% of total HCO3- absorption in mid to late proximal convolutions. This mechanism is stimulated by an increase in ambient HCO(-3) concentration to a degree that might account for the load-dependency of proximal HCO(-3) absorption in these segments of the proximal tubule.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of acute changes in glomerular filtration rate on Na+/H+ exchange in rat renal cortex.

“…One must be cautious in extrapolating from membrane vesicle data to the intact nephron, but our results suggest that only part of the increase in reabsorption seen over the range of filtered loads studied can be accounted for on the basis of a change in Na+/ H+ exchange activity measured in vesicles. Bank and coworkers (14) have shown that Na+-independent H+ secretion (presumably via H+-ATPase) is stimulated as well by increasing bicarbonate delivery to the proximal tubular epithelium in the rat. It is conceivable that H+-ATPase plays a larger role in stimulating bicarbonate reabsorption at high filtered loads, but further studies are needed to answer this question.…”

“…Two epithelial transporters, the Na+/H+ exchanger and the H+-ATPase, drive proximal tubular bicarbonate reabsorption. Ofthese, the Na+/H+ exchanger is probably responsible for the majority of bicarbonate reabsorption under control conditions (14)(15)(16). Indirect evidence from nephron deletion studies suggests that this transporter is stimulated by increased delivery under conditions where single-nephron (SN)GFR is increased, but in none of these studies was bicarbonate delivery actually measured (17)(18)(19).…”

Expression and distribution of renal vacuolar proton-translocating adenosine triphosphatase in response to chronic acid and alkali loads in the rat.

“…Intercalated cells showing H' ATPase staining: A, apically stained; B, basolaterally stained; BA, basolateral and apical pole staining; D, diffusely stained; PPA, poorly polarized apically stained; PPB, poorly polarized basolaterally stained; WPA, wellpolarized apically stained; WPB, well-polarized basolaterally stained. ent in the apical membrane (2-4), contributes to up to 40% of the overall proximal H' secretion in rat (5)(6)(7). Physiologic studies have revealed increased or reduced Na+/H+ antiport activity and bicarbonate reabsorption in the proximal tubule in response, respectively, to metabolic acidosis (8)(9)(10)(11)(12)(13)(14) or metabolic alkalosis (12,13).…”

Developmental Changes in Rabbit Juxtamedullary Proximal Convoluted Tubule Acidification

“…There is evidence that proton secretion in the adult PCT may, in part, be mediated by a sodium-independent H+-ATPase on the apical membrane (16)(17)(18)(19)(20)(21). In S3 proximal straight tubules from adult rabbits, this transporter is present and is an important mechanism for the defense of cell pH from an acid load (19).…”