Control of active proton transport in turtle urinary bladder by cell pH.

103

A B S T R A C T The effects of systemic bicarbonate concentration and extracellular fluid volume status on proximal tubular bicarbonate absorption, independent of changes in luminal composition and flow rate, were examined with in vivo luminal microperfusion of rat superficial proximal convoluted tubules. Net bicarbonate absorption and bicarbonate permeability were measured using microcalorimetry. From these data, net bicarbonate absorption was divided into two parallel components: proton secretion and passive bicarbonate diffusion.The rate of net bicarbonate absorption was similar in hydropenic and volume-expanded rats when tubules were perfused with 24 mM bicarbonate, but was inhibited in volume-expanded rats when tubules were perfused with 5 mM bicarbonate. Volume expansion caused a 50% increase in bicarbonate permeability, which totally accounted for the above inhibition. The rate of proton secretion was unaffected by volume expansion in both studies.The rate of net bicarbonate absorption was markedly inhibited in alkalotic expansion as compared with isohydric expansion. Bicarbonate permeabilities were not different in these two conditions, and the calculated rates of proton secretion were decreased by >50% in alkalosis. Net bicarbonate absorption was stimulated in acidotic rats compared to hydropenic rats. This stimulation was attributable to a 25% increase in the rate of proton secretion.We conclude that (a) proton secretion is stimulatedPortions of this study were presented at the 13th, 14th, and 15th Annual Meetings of the American Society of Nephrology and were published in abstract

Section: Resultssupporting

confidence: 82%

Section: Resultsmentioning

confidence: 99%

Effects of extracellular fluid volume and plasma bicarbonate concentration on proximal acidification in the rat.

Alpern¹,

Cogan²,

Rector³

1983

103

“…This thesis, that peritubular alkalinity suppressed proximal hydrogen ion secretion, is consonant with observations of split droplet studies in the proximal tubule (4,21), of in vivo microperfusion studies (20) and in vitro microperfusion studies (22) using proximal tubules, as well as of studies using the turtle bladder (23). Thus, suppression of acidification by peritubular alkalinity may explain why reabsorptive saturation was observed in the proximal tubule as filtered bicarbonate concentration was simultaneously increased, and similarly why a reabsorptive plateau (a "Tm") has been observed in the whole kidney during bicarbonate titration studies (2).…”

Section: Resultssupporting

confidence: 71%

Metabolic alkalosis in the rat. Evidence that reduced glomerular filtration rather than enhanced tubular bicarbonate reabsorption is responsible for maintaining the alkalotic state.

Cogan¹,

Liu²

1983

A B S T R A C T Maintenance of chronic metabolic alkalosis might occur by a reduction in glomerular filtration rate (GFR) without increased bicarbonate reabsorption or, alternatively, by augmentation of bicarbonate reabsorption with a normal GFR. To differentiate these possibilities, free-flow micropuncture was performed in alkalotic Munich-Wistar rats with a glomerular ultrafiltrate total CO2 concentration of 46.5±0.9 mM (vs. 27.7±0.9 mM in controls). Alkalotic animals had a markedly reduced single nephron GFR compared with controls (27.4±1.5 vs. 51.6±1.6 nl/min) and consequently unchanged filtered load of bicarbonate. Absolute proximal bicarbonate reabsorption in alkalotic animals was similar to controls (981±49 vs. 1,081±57 pmol/min), despite a higher luminal bicarbonate concentration, contracted extracellular volume, and potassium depletion. When single nephron GFR during alkalosis was increased toward normal by isohydric volume expansion or in another group by isotonic bicarbonate loading, absolute proximal bicarbonate reabsorption was not substantially augmented and bicarbonaturia developed. To confirm that a fall in GFR occurs during metabolic alkalosis, additional clearance studies were performed. Awake rats were studied before and after induction of metabolic alkalosis associated with varying amounts of potassium Portions of this work were presented at the National Meet-

“…Bicarbonate absorption by both the turtle bladder and the CCT is electrogenic (6,11,(32)(33)(34)(35). Most data suggest that protons are electrogenically pumped into the lumen by an apical membrane proton translocating adenosine triphosphatase leaving OH-ions in the cell (35)(36)(37)(38)(39).…”

Section: Discussionmentioning

confidence: 99%

“…Most data suggest that protons are electrogenically pumped into the lumen by an apical membrane proton translocating adenosine triphosphatase leaving OH-ions in the cell (35)(36)(37)(38)(39). Since HCO-absorption is inhibited by low CO2 tensions and acetazolamide (8,(32)(33)(34)36) it is likely that the intracellular OH-is carboxylated by C02, in a carbonic anhydrase facilitated step, to form HCO5, which then exits the cell. HCO-absorption is inhibited by the removal ofperitubular Cl-so it has been postulated that basolateral HCO-exit is mediated by a Cl-/HCO-exchanger (40, 41).…”

Section: Discussionmentioning

confidence: 99%

Regulation of net bicarbonate transport in rabbit cortical collecting tubule by peritubular pH, carbon dioxide tension, and bicarbonate concentration.

Breyer¹,

Kokko²,

Jacobson³

1986

The effects of changes in peritubular pH, carbon dioxide tension (Pco2), and HCO3 concentration on net HCO3 transport was examined in in vitro perfused cortical collecting tubules (CCTs) from unpretreated New Zealand white rabbits. Lowering peritubular HCO3 concentration and pH by reciprocal replacement of HCO3 with Cl-, significantly stimulated net HCO3 absorption. Lowering peritubular HCO3 concentration and pH, by substitution of HCO3 with gluconate, while keeping Cl-concentration constant, also stimulated net HCO3 absorption. Raising peritubular HCO3 concentration and pH, by reciprocal replacement of Cl-with HCO3, inhibited net HCO3 absorption (or stimulated net HCO3 secretion). When the tubule was cooled, raising peritubular HCO3 concentration had no effect on net HCO3 transport, suggesting these results are not due to the passive flux of HCO3 down its concentration gradient.The effect of changes in ambient Pco2 on net HCO3 transport were also studied. Increasing the ambient Pco2 from 40 mmHg to either 80 or 120 mmHg, allowing pH to fall, had no effect on net HCO3 transport. Similarly, lowering ambient Pco2 to 14 mmHg had no effect on net HCO3 transport. Simultaneously increasing peritubular HCO3 concentration and Pco2, without accompanying changes in peritubular pH, i.e., isohydric changes, stimulated net HCO3 secretion to the same degree as nonisohydric increases in peritubular HCO3 concentration. Likewise, isohydric lowering of peritubular HCO3 concentration and Pco2 stimulated net HCO3 absorption.We conclude that: (a) acute changes in peritubular HCO3 concentration regulate acidification in the CCI and these effects are mediated by a transcellular process; (b) acute changes in ambient Pco2 within the physiologic range have no effect on HCO3 transport in the in vitro perfused CCI; and (c) acute in vitro regulation of CCI acidification is independent of peritubular pH.