Comprehensive Physiology Wiley Online Library
For Librarians For Authors Editors About

Renal Acidification: Cellular Mechanisms of Tubular Transport and Regulation

Robert J. Alpern, Floyd C. Rector

10.1002/cphy.cp080118

Source: Supplement 25: Handbook of Physiology, Renal Physiology

Originally published: 1992

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Newer Techniques
2 Carbonic Anhydrase
3 Mechanisms of Proximal Tubular Acidification
3.1 Apical Membrane
3.2 Basolateral Membrane
3.3 Leak Pathways
3.4 Carbonic Anhydrase
3.5 Summary
4 Mechanisms of Loop of Henle Acidification
5 Mechanisms of Distal Nephron Acidification
5.1 Mechanism of Proton Secretion (Bicarbonate Absorption)
5.2 Mechanism of Bicarbonate Secretion
5.3 Leak Pathways
5.4 Cells Mediating H+/ Transport
5.5 Carbonic Anhydrase
6 Mechanisms of Regulation of Acidification
6.1 Proximal Tubule
6.2 Distal Tubule
Figure 1. Figure 1.

Mechanisms of luminal fluid acidification: proton secretion (a), and direct bicarbonate absorption (b).

From 18
Figure 2. Figure 2.

Effect of rapidly lowering bicarbonate concentration in extracellular fluid on cell PD. (a) Changing peritubular bicarbonate concentration leads to rapid depolarization of the cell followed by slow recovery. (b) Changing luminal bicarbonate concentration has only a small effect on cell potential.

From 55
Figure 3. Figure 3.

Mechanism of proton secretion in proximal tubule.
Figure 4. Figure 4.

Mechanism of proton secretion (bicarbonate absorption) in distal nephron.

From 18
Figure 5. Figure 5.

Mechanisms of bicarbonate secretion in cortical collecting tubule and turtle urinary bladder. (a) Electroneutral bicarbonate secretion. (b) Electrogenic bicarbonate secretion.
Figure 6. Figure 6.

Transmission electron micrographs of cortical collecting tubule cells from normal rat. (a) Type A cell. Numerous tubulovesicular structures are present in the apical region. Magnification × 12,000. (b) Type B cell. Tubulovesicular structures are present throughout the cell, and the basal plasma membrane exhibits numerous infoldings. A band of cytoplasm free of organelles is present under the apical membrane. Magnification × 10,000.

Courtesy of Dr. Kirsten M. Madsen
Figure 7. Figure 7.

Scanning electron micrograph from rat cortical collecting duct illustrating surface configuration of type A (solid arrows) and type B (open arrows) intercalated cell. Magnification × 12,500.

Courtesy of Dr. Jill W. Verlander
Figure 8. Figure 8.

Dependence of proximal tubular bicarbonate absorption on luminal bicarbonate concentration. Net bicarbonate absorption (solid line) increases as luminal bicarbonate concentration increases. Corrected for the calculated rate of passive bicarbonate diffusion (shaded area), the rate of active proton secretion (dashed line) increases with increasing luminal bicarbonate concentrations below 45 mEq/liter and then plateaus.

From 14
Figure 9. Figure 9.

Effect of stimulation or inhibition of proton secretion on net bicarbonate absorption along the entire proximal tubule in a computer simulation of proximal tubular acidification. When rate of proton secretion is stimulated or inhibited (abscissa), the effect on net bicarbonate absorption along the entire proximal tubule (ordinate) is smaller than the percentage stimulation or inhibition of proton secretion. This attenuating effect is greatest at low plasma bicarbonate concentrations (A), and low glomerular filtration rates (B).

From 17
Figure 10. Figure 10.

Effect of luminal flow rate on net bicarbonate absorption expressed as a function of mean luminal bicarbonate concentration. Closed circles and solid line represent tubules perfused at 15 nl/min. Open circle and triangle represent tubules perfused with 25 mEq/liter bicarbonate at 33 nl/min and at 49 nl/min.

From 16
Figure 11. Figure 11.

Rate of proton secretion plotted as function of mean luminal bicarbonate concentration. (a) Solid line represents tubules perfused at 15 nl/min; dashed line, tubules perfused at 49 nl/min. (b) Solid line represents tubules with peritubular bicarbonate concentration equal to 24 mEq/liter; dashed line, those with peritubular bicarbonate concentration equal to 37 mEq/liter. (c) Solid line represents tubules with a rate of volume absorption of 2 nl/mm·min; dashed line, tubules with no volume absorption.

From 9
Figure 12. Figure 12.

Transmission electron micrographs depicting apical region of intercalated cells from outer medullary collecting duct. (a) Normal rat. Tubulovesicular structures are present in the cytoplasm. Magnification × 48,000. (b) Rat with acute respiratory acidosis. Note absence of tubulovesicular structures in the cytoplasm. Magnification × 48,000.

Courtesy of Dr. Kirsten M. Madsen


Figure 1.

Mechanisms of luminal fluid acidification: proton secretion (a), and direct bicarbonate absorption (b).

From 18


Figure 2.

Effect of rapidly lowering bicarbonate concentration in extracellular fluid on cell PD. (a) Changing peritubular bicarbonate concentration leads to rapid depolarization of the cell followed by slow recovery. (b) Changing luminal bicarbonate concentration has only a small effect on cell potential.

From 55


Figure 3.

Mechanism of proton secretion in proximal tubule.



Figure 4.

Mechanism of proton secretion (bicarbonate absorption) in distal nephron.

From 18


Figure 5.

Mechanisms of bicarbonate secretion in cortical collecting tubule and turtle urinary bladder. (a) Electroneutral bicarbonate secretion. (b) Electrogenic bicarbonate secretion.



Figure 6.

Transmission electron micrographs of cortical collecting tubule cells from normal rat. (a) Type A cell. Numerous tubulovesicular structures are present in the apical region. Magnification × 12,000. (b) Type B cell. Tubulovesicular structures are present throughout the cell, and the basal plasma membrane exhibits numerous infoldings. A band of cytoplasm free of organelles is present under the apical membrane. Magnification × 10,000.

Courtesy of Dr. Kirsten M. Madsen


Figure 7.

Scanning electron micrograph from rat cortical collecting duct illustrating surface configuration of type A (solid arrows) and type B (open arrows) intercalated cell. Magnification × 12,500.

Courtesy of Dr. Jill W. Verlander


Figure 8.

Dependence of proximal tubular bicarbonate absorption on luminal bicarbonate concentration. Net bicarbonate absorption (solid line) increases as luminal bicarbonate concentration increases. Corrected for the calculated rate of passive bicarbonate diffusion (shaded area), the rate of active proton secretion (dashed line) increases with increasing luminal bicarbonate concentrations below 45 mEq/liter and then plateaus.

From 14


Figure 9.

Effect of stimulation or inhibition of proton secretion on net bicarbonate absorption along the entire proximal tubule in a computer simulation of proximal tubular acidification. When rate of proton secretion is stimulated or inhibited (abscissa), the effect on net bicarbonate absorption along the entire proximal tubule (ordinate) is smaller than the percentage stimulation or inhibition of proton secretion. This attenuating effect is greatest at low plasma bicarbonate concentrations (A), and low glomerular filtration rates (B).

From 17


Figure 10.

Effect of luminal flow rate on net bicarbonate absorption expressed as a function of mean luminal bicarbonate concentration. Closed circles and solid line represent tubules perfused at 15 nl/min. Open circle and triangle represent tubules perfused with 25 mEq/liter bicarbonate at 33 nl/min and at 49 nl/min.

From 16


Figure 11.

Rate of proton secretion plotted as function of mean luminal bicarbonate concentration. (a) Solid line represents tubules perfused at 15 nl/min; dashed line, tubules perfused at 49 nl/min. (b) Solid line represents tubules with peritubular bicarbonate concentration equal to 24 mEq/liter; dashed line, those with peritubular bicarbonate concentration equal to 37 mEq/liter. (c) Solid line represents tubules with a rate of volume absorption of 2 nl/mm·min; dashed line, tubules with no volume absorption.

From 9


Figure 12.

Transmission electron micrographs depicting apical region of intercalated cells from outer medullary collecting duct. (a) Normal rat. Tubulovesicular structures are present in the cytoplasm. Magnification × 48,000. (b) Rat with acute respiratory acidosis. Note absence of tubulovesicular structures in the cytoplasm. Magnification × 48,000.

Courtesy of Dr. Kirsten M. Madsen
References
 1. Adam, W. R., A. P. Koretsky, and M. W. Weiner. 31P‐NMR in vivo measurement of renal intracellular pH: effects of acidosis and K+ depletion in rats. Am. J. Physiol. 251 (Renal Fluid Electrolyte Physiol. 20): F904–F910, 1986.
 2. Adler, S., A. Roy, and A. S. Relman. Intracellular acid‐base regulation. I. The response of muscle cells to changes in CO2 tension or extracellular bicarbonate concentration. J. Clin. Invest. 44: 8–20, 1965.
 3. Adler, S., E. Shoubridge, and G. K. Radda. Estimation of cellular pH gradients with 31P‐NMR in intact rabbit renal tubular cells. Am. J. Physiol. 247 (Cell Physiol. 16): Cl88–Cl96, 1984.
 4. Akiba, T., R. J. Alpern, J. Eveloff, J. Calamina, and D. G. Warnock. Electrogenic sodium/bicarbonate cotransport in rabbit renal cortical basolateral membrane vesicles. J. Clin. Invest. 78: 1472–1478, 1986.
 5. Akiba, T., V. Rocco, and D. G. Warnock. Parallel adaptation of the rabbit renal cortical Na/H antiporter and Na/HCO3 cotransporter in subacute metabolic acidosis and alkalosis. Kidney Int. 31: 404, 1987 (abstr.).
 6. Al‐Awqati, Q. Effect of aldosterone on the coupling between H+ transport and glucose oxidation. J. Clin. Invest. 60: 1240–1247, 1977.
 7. Al‐Awqati, Q., A. Mueller, and P. R. Steinmetz. Transport of H+ against electrochemical gradients in turtle urinary bladder. Am. J. Physiol. 233 (Renal Fluid Electrolyte Physiol. 2): F502–F508, 1977.
 8. Al‐Awqati, Q., L. H. Norby, A. Mueller, and P. R. Steinmetz. Characteristics of stimulation of H+ transport by aldosterone in turtle urinary bladder. J. Clin. Invest. 58: 351–358, 1976.
 9. Alpern, R. J. Bicarbonate‐water interactions in the rat proximal convoluted tubule: an effect of volume flux on active proton secretion. J. Gen. Physiol. 84: 753–770, 1984.
 10. Alpern, R. J. Mechanism of basolateral membrane H+/OH−/ transport in the rat proximal convoluted tubule: a sodium‐coupled electrogenic process. J. Gen. Physiol. 86: 613–637, 1985.
 11. Alpern, R. J. Apical membrane Cl/base exchange in the rat proximal convoluted tubule. J. Clin. Invest. 79: 1026–1030, 1987.
 12. Alpern, R. J., and M. Chambers. Cell pH in the rat proximal convoluted tubule: regulation by luminal and peritubular pH and sodium concentration. J. Clin. Invest. 78: 502–510, 1986.
 13. Alpern, R. M., and M. Chambers. Basolateral membrane Cl/HCO3 exchange in the rat proximal convoluted tubule: Na‐dependent and independent modes. J. Gen. Physiol. 89: 581–598, 1987.
 14. Alpern, R. J., M. G. Cogan, and F. C. Rector, Jr. Effect of luminal bicarbonate concentration on proximal acidification in the rat. Am. J. Physiol. 243 (Renal Fluid Electrolyte Physiol. 12): F53–F59, 1982.
 15. Alpern, R. J., M. G. Cogan, and F. C. Rector, Jr. Effects of extracellular fluid volume and plasma bicarbonate concentration on proximal acidification in the rat. J. Clin. Invest. 71: 736–746, 1983.
 16. Alpern, R. J., M. G. Cogan, and F. C. Rector, Jr. Flow dependence of proximal tubular bicarbonate absorption. Am. J. Physiol. 245 (Renal Fluid Electrolyte Physiol. 14): F478–F484, 1983.
 17. Alpern, R. J., and F. C. Rector, Jr. A model of proximal tubular bicarbonate absorption. Am. J. Physiol. 248 (Renal Fluid Electrolyte Physiol. 17): F272–F281, 1985.
 18. Alpern, R. J., D. G. Warnock, and F. C. Rector, Jr. Acidification mechanisms. In: The Kidney (3rd ed.), edited by B. M. Brenner and F. C. Rector, Jr. Philadelphia: Saunders, 1986, p. 206–249.
 19. Ammann, D., F. Lanter, R. A. Steiner, P. Schulthess, Y. Shijo, and W. Simon. Neutral carrier based hydrogen ion selective microelectrode for extra‐ and intracellular studies. Anal. Chem. 53: 2267–2269, 1981.
 20. Aronson, P. S. Mechanisms of active H+ secretion in the proximal tubule. Am. J. Physiol. 245 (Renal Fluid Electrolyte Physiol. 14): F647–F659, 1983.
 21. Aronson, P. S., J. Nee, and M. A. Suhm. Modifier role of internal H+ in activating the Na+‐H+ exchanger in renal microvillus membrane vesicles. Nature 299: 161–163, 1982.
 22. Aronson, P. S., M. A. Suhm, and J. Nee. Interaction of external H+ with the Na+‐H+ exchanger in renal microvillus membrane vesicles. J. Biol. Chem. 258: 6767–6771, 1983.
 23. Atkins, J. L. and M. B. Burg. Bicarbonate transport by isolated perfused rat collecting ducts. Am. J. Physiol. 249 (Renal Fluid Electrolyte Physiol. 18): F485–F489, 1985.
 24. Bank, N., and H. S. Aynedjian. A micropuncture study of the effect of parathyroid hormone on renal bicarbonate reabsorption. J. Clin. Invest. 58: 336–344, 1976.
 25. Bank, N., H. S. Aynedjian, and B. F. Mutz. Evidence for a DCCD‐sensitive component of proximal bicarbonate reabsorption. Am. J. Physiol. 249 (Renal Fluid Electrolyte Physiol. 18): F636–F644, 1985.
 26. Bank, N., and W. B. Schwartz. The influence of anion penetrating ability on urinary acidification and the excretion of titratable acid. J. Clin. Invest. 39: 1516–1525, 1960.
 27. Barfuss, D. W., and J. A. Schafer. Flow dependence of nonelectrolyte absorption in the nephron. Am. J. Physiol. 236 (Renal Fluid Electrolyte Physiol. 5): F163–F174, 1982.
 28. Baum, M. Evidence that parallel Na+/H+ and Cl−/(OH−) antiporters transport NaCl in the rabbit proximal convoluted tubule. Am. J. Physiol. 252 (Renal Fluid Electrolyte Physiol. 21): F338–F345, 1987.
 29. Baylis, C., and B. M. Brenner. Mechanism of the glucocorticoid‐induced increase in glomerular filtration rate. Am. J. Physiol. 234 (Renal Fluid Electrolyte Physiol. 3): F166–F170, 1978.
 30. Becker, B. F., and J. Duhm. Evidence for anionic cation transport of lithium, sodium and potassium across the human erythrocyte membrane induced by divalent anions. J. Physiol. 282: 149–168, 1978.
 31. Bengele, H. H., L. Graber, and E. A. Alexander. Effect of respiratory acidosis on acidification by the medullary collecting duct. Am. J. Physiol. 244 (Renal Fluid Electrolyte Physiol. 13): F89–F94, 1983.
 32. Bengele, H. H., E. R. McNamara, and E. A. Alexander. Effect of acute thyroparathyroidectomy on nephron acidification. Am. J. Physiol. 246 (Renal Fluid Electrolyte Physiol. 15): F569–F574, 1984.
 33. Bengele, H. H., J. H. Schwartz, E. R. McNamara, and E. A. Alexander. Effect of buffer infusion during acute respiratory acidosis. Am. J. Physiol. 250 (Renal Fluid Electrolyte Physiol. 19): F115–F119, 1986.
 34. Berry, C. A. Electrical effects of acidification in the rabbit proximal convoluted tubule. Am. J. Physiol. 240 (Renal Fluid Electrolyte Physiol. 9): F459–F470, 1981.
 35. Berry, C. A. Lack of effect of peritubular protein on passive NaC1 transport in the rabbit proximal tubule. J. Clin. Invest. 71: 268–281, 1983.
 36. Berry, C. A., and M. G. Cogan. Influence of peritubular protein on solute absorption in the rabbit proximal tubule: a specific effect on NaCl transport. J. Clin. Invest. 68: 506–516, 1981.
 37. Berry, C. A., D. G. Warnock, and F. C. Rector, Jr. Ion selectivity and proximal salt reabsorption. Am. J. Physiol. 235 (Renal Fluid Electrolyte Physiol. 4): F234–F245, 1978.
 38. Biagi, B. A. Effects of the anion transport inhibitor, SITS, on the proximal straight tubule of the rabbit perfused in vitro. J. Membr. Biol. 88: 25–31, 1985.
 39. Biagi, B., T. Kubota, M. Sohtell, and G. Giebisch. Intracellular potentials in rabbit proximal tubules perfused in vitro. Am. J. Physiol. 240 (Renal Fluid Electrolyte Physiol. 9); F200–F210, 1981.
 40. Biagi, B. A., and M. Sohtell. pH sensitivity of the basolateral membrane of the rabbit proximal tubule. Am. J. Physiol. 250 (Renal Fluid Electrolyte Physiol. 19): F261–F266, 1986.
 41. Biagi, B. A., and M. Sohtell. Electrophysiology of basolateral bicarbonate transport in the rabbit proximal tubule. Am. J. Physiol. 250 (Renal Fluid Electrolyte Physiol. 19): F267–F272, 1986.
 42. Bichara, M., O. Mercier, M. Paillard, and F. Leviel. Effects of parathyroid hormone on urinary acidification. Am. J. Physiol. 251 (Renal Fluid Electrolyte Physiol. 20): F444–F453, 1986.
 43. Bichara, M., M. Paillard, B. Corman, C. deRouffingnac, and F. Leviel. Volume expansion modulates NaHCO3 and NaCl transport in the proximal tubule and Henle's loop. Am. J. Physiol. 247 (Renal Fluid Electrolyte Physiol. 16): F140–F150, 1984.
 44. Boron, W. F., and E. L. Boulpaep. Intracellular pH regulation in the renal proximal tubule of the salamander: Na‐H exchange. J. Gen. Physiol. 81: 29–52, 1983.
 45. Boron, W. F., and E. L. Boulpaep. Intracellular pH regulation in the renal proximal tubule of the salamander: basolateral transport. J. Gen. Physiol. 81: 53–94, 1983.
 46. Boulpape, E. L. Permeability changes of the proximal tubule of Necturus during saline loading. Am. J. Physiol. 222: 517–531, 1972.
 47. Brazy, P. C., and R. B. Gunn. Furosemide inhibition of chloride transport in human red blood cells. J. Gen. Physiol. 68: 583–599, 1976.
 48. Breyer, M. D., J. P. Kokko, and H. R. Jacobson. Regulation of net bicarbonate transport in rabbit cortical collecting tubule by peritubular pH, carbon dioxide tension, and bicarbonate concentration. J. Clin. Invest. 77: 1650–1660, 1986.
 49. Breyer, M. D., H. R. Jacobson. Regulation of rabbit medullary collecting duct cell pH by basolateral Na+/H+ and Cl−/base exchange. J. Clin. Invest. 84: 996–1004, 1989.
 50. Brown, D., S. Gluck, and J. Hartwig. The studded “coat” of mitochondria‐rich (MR) cell plasma and tubulovesicle membranes is an H+ATPase. Kidney Int. 31: 162, 1987 (abstr.)
 51. Brown, D., and L. Orci. The coat of kidney intercalated cell tubulovesicles does not contain clathrin. Am. J. Physiol. 250 (Cell Physiol. 19): C605–C608, 1986.
 52. Brown, D., J. Roth, T. Kumpulainen, and L. Orci. Ultrastructural immunocytochemical localization of carbonic anhydrase: presence in intercalated cells of the rat collecting tubule. Histochemistry 75: 209–213, 1982.
 53. Buerkert, J., D. Martin, and D. Trigg. Segmental analysis of the renal tubule in buffer production and net acid formation. Am. J. Physiol. 244 (Renal Fluid Electrolyte Physiol. 13): F442–F454, 1983.
 54. Burckhardt, B.‐Ch., A. C. Cassola, and E. Fromter. Electrophysiological analysis of bicarbonate permeation across the peritubular cell membrane of rat kidney proximal tubule. II. Exclusion of ‐effects on other ion permeabilities and of coupled electroneutral HCO3 ‐transport. Pflugers Arch. 401: 43–51, 1984.
 55. Burckhardt, B.‐Ch., K. Sato, and E. Fromter. Electrophysiological analysis of bicarbonate permeation across the peritubular cell membrane of rat kidney proximal tubule. I. Basic observations. Pflugers Arch. 401: 34–42, 1984.
 56. Burg, M. B. Introduction: background and development of microperfusion technique. Kidney Int. 22: 417–424, 1982.
 57. Burg, M., and N. Green. Bicarbonate transport by isolated perfused rabbit proximal convoluted tubules. Am. J. Physiol. 233 (Renal Fluid Electrolyte Physiol. 2): F307–F314, 1977.
 58. Burnham, C., C. Munzesheimer, E. Rabon, and G. Sachs. Ion pathways in renal brush border membranes. Biochim. Biophys. Acta 685: 260–272, 1982.
 59. Cabantchik, Z. I., P. A. Knauf, and A. Rothstein. The anion transport system of the red blood cell: the role of membrane protein evaluated by the use of probes. Biochim. Biophys. Acta 515: 239–302, 1978.
 60. Cabantchik, Z. I., and A. Rothstein. The nature of the membrane sites controlling anion permeatiliby of human red blood cells as determined by studies with disulfonic stilbene derivatives. J. Membr. Biol. 10: 311–330, 1972.
 61. Cannon, C., J. van Adelsberg, S. Kelly, and Q. Al‐Awqati. Carbon‐dioxide‐induced exocytotic insertion of H+ pumps in turtle bladder luminal membrane: role of cell pH and calcium. Nature 314: 443–446, 1985.
 62. Capasso, G., R. Kinne, G. Malnic, and G. Giebisch. Renal bicarbonate reabsorption in the rat. I. Effects of hypokalemia and carbonic anhydrase. J. Clin. Invest. 78: 1558–1567, 1986.
 63. Cassola, A. C., M. Mollenhauer, and E. Fromter. The intracellular chloride activity of rat kidney proximal tubular cells. Pflugers Arch. 399: 259–265, 1983.
 64. Chabardes, D., M. Imbert, A. Clique, M. Montegut, and F. Morel. PTH sensitive adenyl cyclase activity in different segments of the rabbit nephron. Pflugers Arch. 354: 229–239, 1975.
 65. Chaillet, J. R., and W. F. Boron. Intracellular pH regulation in rabbit proximal tubules studied with a pH‐sensitive dye. Kidney Int. 25: 273, 1984 (abstr.).
 66. Chaillet, J. R., and W. F. Boron. Intracellular calibration of a pH‐sensitive dye in isolated, perfused salamander proximal tubules. J. Gen. Physiol. 86: 765–794, 1985.
 67. Chaillet, J. R., A. G. Lopes, and W. F. Boron. Basolateral Na‐H exchange in the rabbit cortical collecting tubule. J. Gen. Physiol. 86: 795–812, 1985.
 68. Chan, Y. L., B. Biagi, and G. Giebisch. Control mechanisms of bicarbonate transport across the rat proximal convoluted tubule. Am. J. Physiol. 242 (Renal Fluid Electrolyte Physiol. 11): F532–F543, 1982.
 69. Chan, Y. L., and G. Giebisch. Relationship between sodium and bicarbonate transport in the rat proximal convoluted tubule. Am. J. Physiol. 240 (Renal Fluid Electrolyte Physiol. 9): F222–F230, 1981.
 70. Chan, Y. L., G. Malnic, and G. Giebisch. Passive driving forces of proximal tubular fluid and bicarbonate transport: gradient‐dependence of H+ secretion. Am. J. Physiol. 245 (Renal Fluid Electrolyte Physiol. 14): F622–F633, 1983.
 71. Chantrelle, B., M. B. Cogan, and F. C. Rector, Jr. Evidence for coupled sodium/hydrogen exchange in the rat superficial proximal convoluted tubule. Pflugers Arch. 395: 186–189, 1982.
 72. Chase, H. S., and Q. Al‐Awqati. Calcium reduces the sodium permeability of luminal membrane vesicles from toad bladder: studies using a fast‐reaction apparatus. J. Gen. Physiol. 81: 643–665, 1983.
 73. Cogan, M. G. Volume expansion predominantly inhibits proximal reabsorption of NaCl rather than NaHCO3. Am. J. Physiol. 245 (Renal Fluid Electrolyte Physiol. 14): F272–F275, 1983.
 74. Cocan, M. G. Effects of acute alterations in PCO2 on proximal , Cl−, and H2O reabsorption. Am. J. Physiol. 246 (Renal Fluid Electrolyte Physiol. 15): F21–F26, 1984.
 75. Cogan, M. G. Chronic hypercapnia stimulates proximal bicarbonate reabsorption in the rat. J. Clin. Invest. 74: 1942–1947, 1984.
 76. Cogan, M. G., and R. J. Alpern. Regulation of proximal bicarbonate reabsorption. Am. J. Physiol. 247 (Renal Fluid Electrolyte Physiol. 16): F387–F395, 1984.
 77. Cogan, M. G., D. A. Maddox, M. S. Lucci, and F. C. Rector, Jr. Control of proximal bicarbonate reabsorption in normal and acidotic rats. J. Clin. Invest. 64: 1168–1180, 1979.
 78. Cogan, M. G., D. A. Maddox, D. G. Warnock, E. T. Lin, and F. C. Rector, Jr. Effect of acetazolamide on bicarbonate reabsorption in the proximal tubule of the rat. Am. J. Physiol. 237 (Renal Fluid Electrolyte Physiol. 6): F447–F454, 1979.
 79. Cohen, L. H., A. Mueller, and P. R. Steinmetz. Inhibition of the bicarbonate exit step in urinary acidification by a disulfonic stilbene. J. Clin. Invest. 61: 981–986, 1978.
 80. Cohn, D. E., K. A. Hruska, S. Klahr, and M. R. Hammerman. Increased Na+‐H+ exchange in brush border vesicles from dogs with renal failure. Am. J. Physiol. 243 (Renal Fluid Electrolyte Physiol. 12): F293–F299, 1982.
 81. Cohn, D. E., S. Klahr, and M. R. Hammerman. Metabolic acidosis and parathyroidectomy increase Na+/H+ exchange in brush border vesicles. Am. J. Physiol. 245 (Renal Fluid Electrolyte Physiol. 14): F217–F222, 1983.
 82. Corman, B. Streaming potentials and diffusion potentials across rabbit proximal convoluted tubule. Pflugers Arch. 403: 156–163, 1985.
 83. Corman, B., and A. diStefano. Does water drag solutes through kidney proximal tubule? Pflugers Arch. 397: 35–41, 1983.
 84. Cousin, J. L., and R. Motais. The role of carbonic anhydrase inhibitors on anion permeability into ox red blood cell. J. Physiol. (Lond.) 256: 61–80, 1976.
 85. Diaz, F. D., E. F. LaBelle, D. C. Eaton, and T. D. DuBose, Jr. ATP‐dependent proton transport in human renal medulla. Am. J. Physiol. 251 (Renal Fluid Electrolyte Physiol. 20): F297–F302, 1986.
 86. Dobyan, D. C., and R. E. Bulger. Renal carbonic anhydrase. Am. J. Physiol. 243 (Renal Fluid Electrolyte Physiol. 12): F311–F324, 1982.
 87. Dobyan, D. C., L. S. Magill, P. A. Friedman, S. C. Hebert, and R. E. Bulger. Carbonic anhydrase histochemistry in rabbit and mouse kidneys. Anat. Rec. 204: 185–197, 1982.
 88. DuBose, T. D., Jr. Hydrogen ion secretion by the collecting duct as a determinant of the urine to blood PCO2 gradient in alkaline urine. J. Clin. Invest. 69: 145–156, 1982.
 89. DuBose, T. D., L. R. Pucacco, and N. W. Carter. Determination of disequilibrium pH in the rat kidney in vivo: evidence for hydrogen secretion. Am. J. Physiol. 240 (Renal Fluid Electrolyte Physiol. 9): F138–F146, 1981.
 90. DuBose, T. D., Jr., L. R. Pucacco, M. S. Lucci, and N. W. Carter. Micropuncture determination of pH, PCO2, and total CO2 concentration in accessible structures of the rat renal tubule. J. Clin. Invest. 64: 476–482, 1979.
 91. DuBose, T. D., Jr., L. R. Pucacco, D. W. Seldin, N. W. Carter, and J. P. Kokko. Direct determination of PCO2 in the rat renal cortex. J. Clin. Invest. 62: 338–348, 1978.
 92. Edelman, A., M. Bouthier, and T. Anagnostopoulos. Chloride distribution in the proximal convoluted tubule of Necturus kidney. J. Membr. Biol. 62: 7–17, 1981.
 93. Ehrenspeck, G. Effect of 3‐isobutyl‐1‐methylxanthine on transport in turtle bladder: evidence for electrogenic secretion. Biochim. Biophys. Acta 684: 219–227, 1982.
 94. Eveloff, J., E. R. Swenson, and T. H. Maren. Carbonic anhydrase activity of brush border and plasma membranes prepared from rat kidney cortex. Biochem. Pharmacol. 28: 1434–1437, 1979.
 95. Farman, N., A. Vandewalle, and J. P. Bonvalet. Autoradiographic determination of dexamethasone binding sites along the rabbit nephron. Am. J. Physiol. 244 (Renal Fluid Electrolyte Physiol. 13): F325–F334, 1983.
 96. Fischer, J. L., R. F. Husted, and P. R. Steinmetz. Chloride dependence of the HCO3 exit step in urinary acidification by the turtle bladder. Am. J. Physiol. 245 (Renal Fluid Electrolyte Physiol. 14): F564–F568, 1983.
 97. Frazier, L. W. Effects of parathyroid hormone on H+ and NH4+ excretion in toad urinary bladder. J. Membr. Biol. 30: 187–196, 1976.
 98. Freiberg, J. M., J. Kinsella, and B. Sacktor. Glucocorticoids increase the Na+‐H+ exchange and decrease the Na+ gradient‐dependent phosphate‐uptake systems in renal brush border membrane vesicles. Proc. Natl. Acad. Sci. USA 79: 4932–4936, 1982.
 99. Friedman, P. A., and T. A. Andreoli. CO2‐stimulated NaCl absorption in the mouse renal cortical thick ascending limb of Henle: evidence for synchronous Na+/H+ and Cl−/exchange in apical plasma membranes. J. Gen. Physiol. 80: 683–711, 1982.
 100. Friedman, P. A., J. F. Figueiredo, T. Maack, and E. E. Windhager. Sodium‐calcium interactions in the renal proximal convoluted tubule of the rabbit. Am. J. Physiol. 240 (Renal Fluid Electrolyte Physiol. 9): F558–F568, 1981.
 101. Fritsche, C., and J. H. Schwartz. Identification of the bicarbonate secretory cell of the turtle bladder. Am. J. Physiol. 249 (Renal Fluid Electrolyte Physiol. 18): F858–F862, 1985.
 102. Fromter, E. K. Magnitude and significance of the paracellular shunt path in rat kidney proximal tubule. Excerpta Medica Int. Congr. Ser. No. 391, 393–405, 1977.
 103. Fromter, E., and K. Gessner. Active transport potentials, membrane diffusion potentials, and streaming potentials across rat kidney proximal tubule. Pflugers Arch. 351: 85–98, 1974.
 104. Fromter, E., and K. Gessner. Effect of inhibitors and diuretics on electrical potential differences in rat kidney proximal tubule. Pflugers Arch. 357: 209–224, 1975.
 105. Fromter, E., C. W. Muller, and T. Wick. Permeability properties of the proximal tubular epithelium of the rat kidney studied with electrophysiological methods. In: Electrophysiology of Epithelial Cells, edited by G. Giebisch. Stuttgart: Schattauer, 1971, p. 119–146. (Symp. Med. Hoechst.)
 106. Funder, J., D. C. Tosteson, and J. O. Wieth. Effects of bicarbonate on lithium transport in human red cells. J. Gen. Physiol. 71: 721–746, 1978.
 107. Garcia, M. L., J. Benavides, G. Gimenez‐Gallego, and F. Valdivieso. Coupling between reduced nicotinamide adenine dinucleotide oxidation and metabolic transport in renal brush border membrane vesicles. Biochemistry 19: 4840–4843, 1980.
 108. Garcia‐Austt, J., D. W. Good, M. B. Burg, and M. A. Knepper. Deoxycorticosterone‐stimulated bicarbonate secretion in rabbit cortical collecting ducts: effects of luminal chloride removal and in vivo acid loading. Am. J. Physiol. 249 (Renal Fluid Electrolyte Physiol. 18): F205–F212, 1985.
 109. Geibel, J., G. Giebisch, W. F. Boron. Basolateral sodium‐coupled acid‐base transport mechanisms of the rabbit proximal tubule. Am. J. Physiol. 257 (Renal Fluid Electrolyte Physiol. 26): F790–F797, 1989.
 110. Gennari, F. J., C. R. Caflisch, C. Johns, D. A. Maddox, and J. J. Cohen. PCO2 measurements in surface proximal tubules and peritubular capillaries of the rat kidney. Am. J. Physiol. 242 (Renal Fluid Electrolyte Physiol. 11): F78–F85, 1982.
 111. Giebisch, G., G. Malnic, G. B. DeMello, and M. DeMello. Aires. Kinetics of luminal acidification in cortical tubules of the rat kidney. J. Physiol. 267: 571–599, 1977.
 112. Gimenez‐Gallego, G., J. Benavides, M. L. Garcia, and F. Valdivieso. Occurrence of a reduced nicotinamide adenine dinucleotide oxidase activity linked to a cytochrome system in renal brush border membranes. Biochemistry 19: 4834–4839, 1980.
 113. Glickman, J., K. Croen, S. Kelly, and Q. Al‐Awqati. Golgi membranes contain an electrogenic H+ pump in parallel to a chloride conductance. J. Cell Biol. 97: 1303–1308, 1983.
 114. Gluck, S., and Q. Al‐Awqati. An electrogenic proton‐translocating adenosine triphosphatase from bovine kidney medulla. J. Clin. Invest. 73: 1704–1710, 1984.
 115. Gluck, S., C. Cannon, and Q. Al‐Awqati. Exocytosis regulates urinary acidification in turtle bladder by rapid insertion of H+ pumps into the luminal membrane. Proc. Natl. Acad. Sci. USA 79: 4327–4331, 1982.
 116. Gluck, S., S. Hirsch, and D. Brown. Immunocytochemical localization of H+ATPase in rat kidney. Kidney Int. 31: 167, 1987 (abstr.).
 117. Good, D. W. Sodium‐dependent bicarbonate absorption by cortical thick ascending limb of rat kidney. Am. J. Physiol. 248 (Renal Fluid Electrolyte Physiol. 17): F821–F829, 1985.
 118. Good, D. W., M. A. Knepper, and M. B. Burg. Ammonia and bicarbonate transport by thick ascending limb of rat kidney. Am. J. Physiol. 247 (Renal Fluid Electrolyte Physiol. 16): F35–F44, 1984.
 119. Gottschalk, C. W., W. E. Lassiter, and M. Mylle. Localization of urine acidification in the mammalian kidney. Am. J. Physiol. 198: 581, 1960.
 120. Graber, M. L., H. H. Bengele, E. Mroz, C. Lechene, and E. A. Alexander. Acute metabolic acidosis augments collecting duct acidification rate in the rat. Am. J. Physiol. 241 (Renal Fluid Electrolyte Physiol. 10): F669–F676, 1981.
 121. Graber, M. L., H. H. Bengele, J. H. Schwartz, and E. A. Alexander. pH and PCO2 profiles of the rat inner medullary collecting duct. Am. J. Physiol. 241 (Renal Fluid Electrolyte Physiol. 10): F659–F668, 1981.
 122. Graber, M. L., T. E. Dixon, D. Coachman, K. Herring, A. Ruenes, T. Gardner, and E. Pastoriza‐Munoz. Fluorescence identifies an alkaline cell in turtle urinary bladder. Am. J. Physiol. 250 (Renal Fluid Electrolyte Physiol. 19): F159–F168, 1986.
 123. Grandchamp, A., and E. L. Boulpaep. Pressure control of sodium reabsorption and intercellular backflux across proximal kidney tubule. J. Clin. Invest. 54: 69–82, 1974.
 124. Grassl, S. M., and P. S. Aronson. Na+/ co‐transport in basolateral membrane vesicles isolated from rabbit renal cortex. J. Biol. Chem. 261: 8778–8783, 1986.
 125. Grassl, S. M., L. P. Karniski, and P. S. Aronson. Cl‐HCO3 exchange in rabbit renal cortical basolateral membrane vesicles (BLMV). Kidney Int. 27: 282, 1985 (abstr.).
 126. Guggino, W. B., E. L. Boulpaep, and G. Giebisch. Electrical properties of chloride transport across the Necturus proximal tubule. J. Membr. Biol. 65: 185–196, 1982.
 127. Guggino, W. B., R. London, E. L. Boulpaep, and G. Giebisch. Chloride transport across the basolateral cell membrane of the Necturus proximal tubule: dependence on bicarbonate and sodium. J. Membr. Biol. 71: 227–240, 1983.
 128. Gurich, R. W., and D. G. Warnock. Electrically neutral Na+‐H+ exchange in endosomes obtained from rabbit renal cortex. Am. J. Physiol. 251 (Renal Fluid Electrolyte Physiol. 20): F702–F709, 1986.
 129. Gutknecht, J. Proton/hydroxide conductance through lipid bilayer membranes. J. Membr. Biol. 82: 105–112, 1984.
 130. Hamm, L. L., L. R. Pucacco, J. P. Kokko, and H. R. Jacobson. Hydrogen ion (H+) permeability of isolated perfused tubules. Kidney Int. 21: 234, 1982 (abstr.).
 131. Hamm, L. L., L. R. Pucacco, J. P. Kokko, and H. R. Jacobson. Hydrogen ion permeability of the rabbit proximal convoluted tubule. Am. J. Physiol. 246 (Renal Fluid Electrolyte Physiol. 15): F3–F11, 1984.
 132. Harris, R. C., J. L. Seifter, and B. M. Brenner. Adaptation of Na+‐H+ exchange in renal microvillus membrane vesicles: role of dietary protein and uninephrectomy. J. Clin. Invest. 74: 1979–1987, 1984.
 133. Hays, S. R., R. J. Alpern. Basolateral membrane Na+‐independent Cl−/ exchange in the inner stripe of the rabbit outer medullary collecting tubule. J. Gen. Physiol. 95: 347–367, 1990.
 134. Hays, S. R., R. J. Alpern. Apical and basolateral membrane H+ extrusion mechanisms in the inner stripe of the rabbit outer medullary collecting tubule. Am. J. Physiol. 259 (Renal Fluid Electrolyte Physiol. 28): F628–F635, 1990.
 135. Hays, S., J. P. Kokko, and H. R. Jacobson. Hormonal regulation of proton secretion in rabbit medullary collecting duct. J. Clin. Invest. 78: 1279–1286, 1986.
 136. Hays, S. R., D. W. Seldin, J. P. Kokko, and H. R. Jacobson. Effect of K depletion on HCO3 transport across rabbit collecting duct segments. Kidney Int. 368, 1986 (abstr.).
 137. Hinke, J. A. M. Cation selective microelectrodes for intracellular use. In: Glass Electrodes for Hydrogen and Other Cations, edited by G. Eisenman. New York: Dekker. 1967, p. 464–477.
 138. Holmberg, C., J. P. Kokko, and H. R. Jacobson. Determination of chloride and bicarbonate permeabilities in proximal convoluted tubules. Am. J. Physiol. 241 (Renal Fluid Electrolyte Physiol. 10): F386–F394, 1981.
 139. Howlin, K. J., R. J. Alpern, and F. C. Rector, Jr. Amiloride inhibition of proximal tubular acidification. Am. J. Physiol. 248 (Renal Fluid Electrolyte Physiol. 17): F773–F778, 1985.
 140. Hulter, H. N. Effects and interrelationships of PTH, Ca2+, vitamin D, and P, in acid‐base homeostasis. Am. J. Physiol. 248 (Renal Fluid Electrolyte Physiol. 17): F739–F752, 1985.
 141. Hulter, H. N., L. P. Ilnicki, J. A. Harbottle, and A. Sebastian. Impaired renal H+ secretion and NH3 production in mineralocorticoid‐deficient glucocorticoid‐replete dogs. Am. J. Physiol. 232 (Renal Fluid Electrolyte Physiol. 1): F136–F146, 1977.
 142. Hulter, H. N., J. H. Licht, R. D. Glynn, and A. Sebastian. Renal acidosis in mineralocorticoid deficiency is not dependent on NaCl depletion or hyperkalemia. Am. J. Physiol. 236 (Renal Fluid Electrolyte Physiol. 5): F283–F294, 1979.
 143. Hulter, H. N., A. Sebastian, J. F. Sigala, J. H. Licht R. D. Glynn, M. Schambelan, and E. G. Biglieri. Pathogenesis of renal hyperchloremic acidosis resulting from dietary potassium restriction in the dog: role of aldosterone. Am. J. Physiol. 238 (Renal Fluid Electrolyte Physiol. 7): F79–F91, 1980.
 144. Husted, R. F., and E. Eyman. Chloride‐bicarbonate exchange in the urinary bladder of the turtle: independence from sodium ion. Biochim. Biophys. Acta 595: 305–308, 1980.
 145. Husted, R. F., A. L. Mueller, R. G. Kessel, and P. R. Steinmetz. Surface characteristics of carbonic‐anhydrase‐rich cells in turtle urinary bladder. Kidney Int. 19: 491–502, 1981.
 146. Iacovitti, M., L. Nash, L. N. Peterson, J. Rochon, and D. Z. Levine. Distal tubule bicarbonate accumulation in vivo. Effect of flow and transtubular bicarbonate gradients. J. Clin. Invest. 78: 1658–1665, 1986.
 147. Igarashi, P., C. W. Slayman, and P. S. Aronson. Covalent modification of the renal Na/H exchanger by dicyclohexyl‐carbodiimide (DCCD). Kidney Int. 29: 369, 1986 (abstr.).
 148. Iino, Y., and M. B. Burg. Effect of parathyroid hormone on bicarbonate absorption by proximal tubules in vitro. Am. J. Physiol. 236 (Renal Fluid Electrolyte Physiol. 5): F387–F391, 1979.
 149. Iino, Y., and M. B. Burg. Effect of acid‐base status in vivo on bicarbonate transport by rabbit renal tubules in vitro. Jpn. J. Physiol. 31: 99–107, 1981.
 150. Ives, H. E. Proton/hydroxyl permeability of proximal tubule brush border vesicles. Am. J. Physiol. 248 (Renal Fluid Electrolyte Physiol. 17): F78–F86, 1985.
 151. Ives, H. E., P.‐Y. Chen, and A. S. Verkman. Mechanism of coupling between Cl− and OH− transport in renal brush‐border membranes. Biochim. Biophys. Acta 863: 91–100, 1986.
 152. Ives, H. E., V. J. Yee, and D. G. Warnock. Mixed‐type inhibition of the renal Na+/H+ antiporter by Li+ and amiloride: evidence for a modifier site. J. Biol. Chem. 258: 9710–9716, 1983.
 153. Ives, H. E., V. J. Yee, and D. G. Warnock. Asymmetric distribution of the Na+/H+ antiporter in the renal proximal tubule epithelial cell. J. Biol. Chem. 258: 13513–13516, 1983.
 154. Jacobson, H. R. Effects of CO2 and acetazolamide on bicarbonate and fluid transport in rabbit proximal tubules. Am. J. Physiol. 240 (Renal Fluid Electrolyte Physiol. 9): F54–F62, 1981.
 155. Jacobson, H. R. Medullary collecting duct acidification: effects of potassium, HCO3 concentration, and PCO2. J. Clin. Invest. 74: 2107–2114, 1984.
 156. Jacobson, H. R., J. Cardinal, C. A. Berry, B. Corman, D. W. Barfuss, J. Lapointe, E. Bello‐Reuss, S. Sasaki, K. A. Hruska, and J. Seifter. Proximal tubule transport. In: Nephrology, edited by R. R. Robinson. New York: Springer Verlag, 1984, p. 178–185.
 157. Jacobson, H. R., J. P. Kokko, D. W. Seldin, and C. Holmberg. Lack of solvent drag of NaCl and NaHCO3 in rabbit proximal tubules. Am. J. Physiol. 243 (Renal Fluid Electrolyte Physiol. 12): F342–F348, 1982.
 158. Jayakumar, A., L. Cheng, C. T. Liang, and B. Sacktor. Sodium gradient‐dependent calcium uptake in renal basolateral membrane vesicles: effect of parathyroid hormone. J. Biol. Chem. 259: 10827–10833, 1984.
 159. Jentsch, T. J., B. S. Schill, P. Schwartz, H. Matthes, S. K. Keller, and M. Wiederholt. Kidney epithelial cells of monkey origin (BSC‐1) express a sodium bicarbonate cotransport: characterization by 22Na+ flux measurements. J. Biol. Chem. 260: 15554–15560, 1985.
 160. Kannen, K. K., M. Petef, K. Fridborg, H. Cid‐Dresdner, and S. Lovgren. Structure and function of carbonic anhydrases: imidazole binding to human carbonic anhydrase B and the mechanism of action of carbonic anhydrases. FEBS Lett. 73: 115–119, 1977.
 161. Karniski, L. P., and P. S. Aronson. Chloride/formate exchange with formic acid recycling: a mechanism of active chloride transport across epithelial membranes. Proc. Natl. Acad. Sci. USA 82: 6362–6365, 1985.
 162. Kaunitz, J. D., R. D. Gunther, and G. Sachs. Characterization of an electrogenic ATP and chloride‐dependent proton translocating pump from rat renal medulla. J. Biol. Chem. 260: 11567–11573, 1985.
 163. Kinne‐Saffran, E., R. Beauwens, and R. Kinne. An ATP‐driven proton pump in brush‐border membranes from rat renal cortex. J. Membr. Biol. 64: 67–76, 1982.
 164. Kinne‐Saffran, E., and R. Kinne. Presence of a bicarbonate stimulated ATPase in the brush border membranes of the proximal tubule. Proc. Soc. Exp. Biol. Med. 146: 751–753, 1974.
 165. Kinne‐Saffran, E., and R. Kinne. Further evidence for the existence of an intrinsic bicarbonate‐stimulated Mg2+‐ATPase in brush border membranes isolated from rat kidney cortex. J. Membr. Biol. 49: 235–251, 1979.
 166. Kinsella, J. L., and P. S. Aronson. Properties of the Na+‐H+ exchanger in renal microvillus membrane vesicles. Am. J. Physiol. 238 (Renal Fluid Electrolyte Physiol. 7): F461–F469, 1980.
 167. Kinsella, J. L., and P. S. Aronson. Amiloride inhibition of the Na+‐H+ exchanger in renal microvillus membrane vesicles. Am. J. Physiol. 241 (Renal Fluid Electrolyte Physiol. 10): F374–F379, 1981.
 168. Kinsella, J. L., and P. S. Aronson. Interaction of NH4+ and Li+ with the renal microvillus membrane Na+‐H+ exchanger. Am. J. Physiol. 241 (Cell Physiol. 10): C220–C226, 1981.
 169. Kinsella, J. L., T. Cujkid, and B. Sacktor. Na+‐H+ exchange activity in renal brush border membrane vesicles in response to metabolic acidosis: the role of glucocorticoids. Proc. Natl. Acad. Sci. USA 81: 630–634, 1984.
 170. Kinsella, J. L., J. M. Freiberg, and B. Sacktor. Glucocorticoid activation of Na+/H+ exchange in renal brush border vesicles: kinetic effects. Am. J. Physiol. 248 (Renal Fluid Electrolyte Physiol. 17): F233–F239, 1985.
 171. Kinsella, J. L., and B. Sacktor. Na+‐H+ exchange in isolated renal brush border membrane vesicles: regulation by metabolic acidosis and glucocorticoids. In: Hydrogen Ion Transport in Epithelia, edited by J. G. Forte, D. G. Warnock, and F. C. Rector, Jr. New York: John Wiley and Sons, 1984, p. 127–137.
 172. Kinsella, J. L., and B. Sacktor. Thyroid hormones increase Na+‐H+ exchange activity in renal brush border membranes. Proc. Natl. Acad. Sci. USA 82: 3606–3610, 1985.
 173. Knauf, P. A., and A. Rothstein. Chemical modification of membranes. I. Effects of sulfhydryl and amino reactive reagents on anion and cation permeability of the human red blood cell. J. Gen. Physiol. 58: 190–210, 1971.
 174. Knauf, H., M. Sellinger, K. Haag, and U. Wais. Evidence for mitochondrial origin of the ‐ATPase in brush border membranes of rat proximal tubules. Am. J. Physiol. 248 (Renal Fluid Electrolyte Physiol. 17): F389–F395, 1985.
 175. Knepper, M. A., D. W. Good, and M. B. Burg. Mechanism of ammonia secretion by cortical collecting ducts of rabbits. Am. J. Physiol. 247 (Renal Fluid Electrolyte Physiol. 16): F729–F738, 1984.
 176. Knepper, M. A., D. W. Good, and M. B. Burg. Ammonia and bicarbonate transport by rat cortical collecting ducts perfused in vitro. Am. J. Physiol. 249 (Renal Fluid Electrolyte Physiol. 18): F870–F877, 1985.
 177. Koeppen, B. M. Conductive properties of the rabbit outer medullary collecting duct: inner stripe. Am. J. Physiol. 248 (Renal Fluid Electrolyte Physiol. 17): F500–F506, 1985.
 178. Koeppen, B. M. Conductive properties of rabbit outer medullary collecting duct: outer stripe. Am. J. Physiol. 250 (Renal Fluid Electrolyte Physiol. 19): F70–F76, 1986.
 179. Koeppen, B. M., and S. I. Helman. Acidification of luminal fluid by the rabbit cortical collecting tubule perfused in vitro. Am. J. Physiol. 242 (Renal Fluid Electrolyte Physiol. 11): F521–F531, 1982.
 180. Krapf, R. Basolateral membrane H/OH/HCO3 transport in the rat cortical thick ascending limb. Evidence for an electrogenic Na/HCO3 cotransporter in parallel with a Na/H antiporter. J. Clin. Invest. 82: 234–241, 1988.
 181. Krapf, R. Mechanisms of adaptation to chronic respiratory acidosis in the rabbit proximal tubule. J. Clin. Invest. 83: 890–896, 1989.
 182. Krapf, R., R. J. Alpern, F. C. Rector, Jr., and C. A. Berry. Basolateral membrane Na/base cotransport is dependent on CO2/HCO3 in the proximal convoluted tubule. J. Gen. Physiol. 90: 833–853, 1987.
 183. Kunau, R. T., Jr., J. I. Hart, and K. A. Walker. Effect of metabolic acidosis on proximal tubular tCO2 absorption. Am. J. Physiol. 249 (Renal Fluid Electrolyte Physiol. 18): F62–F68, 1985.
 184. Kurtz, I. Basolateral membrane Na+/H+ antiport, Na+/base cotransport, and Na+‐independent Cl−/base exchange in the rabbit S3 proximal tubule. J. Clin. Invest. 83: 616–622, 1989.
 185. Kurtz, I., and R. S. Balaban. Fluorescence emission spectroscopy of 1,4‐dihydroxyphthalonitrile: method for determining intracellular pH in cultured cells. Biophys. J. 48: 499–508, 1985.
 186. Laski, M. E., and N. A. Kurtzman. Characterization of acidification in the cortical and medullary collecting tubule of the rabbit. J. Clin. Invest. 72: 2050–2059, 1983.
 187. Laski, M. E., D. G. Warnock, and F. C. Rector, Jr. Effects of chloride gradients on total CO2 flux in the rabbit cortical collecting tubule. Am. J. Physiol. 244 (Renal Fluid Electrolyte Physiol. 13): F112–F121, 1983.
 188. Lee, C. O., A. Taylor, and E. E. Windhager. Cytosolic calcium ion activity in epithelial cells of Necturus kidney. Nature 287: 859–861, 1980.
 189. Leslie, B. R., J. H. Schwartz, and P. R. Steinmetz. Coupling between Cl− absorption and secretion in turtle urinary bladder. Am. J. Physiol. 225: 610–617, 1973.
 190. Levine, D. Z. Effect of acute hypercapnia on proximal tubular water and bicarbonate absorption. Am. J. Physiol. 221: 1164–1170, 1971.
 191. Levine, D. A. An in vivo microperfusion study of distal tubule bicarbonate reabsorption in normal and ammonium chloride rats. J. Clin. Invest. 75: 588–595, 1985.
 192. Lin, J.‐T., L.‐Y. Chiu, E. Heinz, and E. E. Windhager. Effects of Ca on transport process in rat renal brush border membranes. Kidney Int. 27: 315, 1985 (abstr.).
 193. Lombard, W. E., J. P. Kokko, and H. R. Jacobson. Bicarbonate transport in cortical and outer medullary collecting tubules. Am. J. Physiol. 244 (Renal Fluid Electrolyte Physiol. 13): F289–F296, 1983.
 194. Lonnerholm, G. Histochemical determination of carbonic anhydrase activity in the rat kidney. Acta Physiol. Scand. 81: 433, 1974.
 195. Lonnerholm, G. Histochemical demonstration of carbonic anhydrase in the human kidney. Acta Physiol. Scand. 88: 455, 1973.
 196. Lonnerholm, G. Carbonic anhydrase in the monkey kidney. Histochemistry 78: 195–208, 1983.
 197. Lonnerholm, G., and Y. Ridderstrale. Distribution of carbonic anhydrase in the frog nephron. Acta Physiol. Scand. 88: 455, 1974.
 198. Lonnerholm, G., and Y. Ridderstrale. Intracellular distribution of carbonic anhydrase in the rat kidney. Kidney Int. 17: 162, 1980.
 199. Lonnerholm, G., and P. J. Wistrand. Carbonic anhydrase in the human kidney: a histochemical and immunocytochemical study. Kidney Int. 25: 886–898, 1984.
 200. Lorenzen, M., C. O. Lee, and E. E. Windhager. Cytosolic Ca2+ and Na+ activities in perfused proximal tubules of Necturus kidney. Am. J. Physiol. 247 (Renal Fluid Electrolyte Physiol. 16): F93–F102, 1984.
 201. Low, I., T. Friedrich, and G. Burckhardt. Properties of an anion exchanger in rat renal basolateral membrane vesicles. Am. J. Physiol. 246 (Renal Fluid Electrolyte Physiol. 15): F334–F342, 1984.
 202. Lucci, M. S., and T. D. DuBose, Jr. The role of pH gradients in regulation of proximal bicarbonate reabsorption. Kidney Int. 25: 279, 1984 (abstr.).
 203. Lucci, M. S., L. R. Pucacco, N. W. Carter, and T. D. DuBose, Jr. Direct evaluation of the permeability of the rat proximal convoluted tubule to CO2. Am. J. Physiol. 242 (Renal Fluid Electrolyte Physiol. 11): F470–F476, 1982.
 204. Lucci, M. S., L. R. Pucacco, N. W. Carter, and T. D. DuBose, Jr. Evaluation of bicarbonate transport in the rat distal tubule: effects of acid‐base status. Am. J. Physiol. 243 (Renal Fluid Electrolyte Physiol. 12): F335–F341, 1982.
 205. Lucci, M. S., L. R. Pucacco, T. D. DuBose, Jr., J. P. Kokko, and N. W. Carter. Direct evaluation of acidification by rat proximal tubule: role of carbonic anhydrase. Am. J. Physiol. 238 (Renal Fluid Electrolyte Physiol. 7): F372–F379, 1980.
 206. Lucci, M. S., J. P. Tinker, I. M. Weiner, and T. D. DuBose, Jr. Function of proximal tubular carbonic anhydrase defined by selective inhibition. Am. J. Physiol. 245 (Renal Fluid Electrolyte Physiol. 14): F443–F449, 1983.
 207. Lucci, M. S., and D. G. Warnock. Effects of anion‐transport inhibitors on NaCl reabsorption in the rat superficial proximal convoluted tubule. J. Clin. Invest. 64: 570–579, 1979.
 208. Lucci, M. S., D. G. Warnock, and F. C. Rector, Jr. Carbonic anhydrase‐dependent bicarbonate reabsorption in the rat proximal tubule. Am. J. Physiol. 236 (Renal Fluid Electrolyte Physiol. 5): F58–F65, 1979.
 209. Maddox, D. A., and F. J. Gennari. Load dependence of HCO3 and H2O reabsorption in the early proximal tubule of the Munich‐Wistar rat. Am. J. Physiol. 248 (Renal Fluid Electrolyte Physiol. 17): F113–F121, 1985.
 210. Madsen, K. M., and C. C. Tisher. Cellular response to acute respiratory acidosis in rat medullary collecting duct. Am. J. Physiol. 245 (Renal Fluid Electrolyte Physiol. 14): F670–F679, 1983.
 211. Madsen, K. M., and C. C. Tisher. Response of intercalated cells of rat outer medullary collecting duct to chronic metabolic acidosis. Lab. Invest. 51: 268–276, 1984.
 212. Madsen, K. M., and C. C. Tisher. Structural‐functional relationships along the distal nephron. Am. J. Physiol. 250 (Renal Fluid Electrolyte Physiol. 19): F1–F15, 1986.
 213. Malnic, G., and M. DeMello‐Aires. Kinetic study of bicarbonate reabsorption in proximal tubule of the rat. Am. J. Physiol. 220: 1759–1767, 1971.
 214. Malnic, G., M. DeMello‐Aires, and G. Giebisch. Micropuncture study of renal tubular hydrogen ion transport in the rat. Am. J. Physiol. 222: 147–158, 1972.
 215. Maren, T. H. Carbonic anhydrase: chemistry, physiology, and inhibition. Physiol. Rev. 47: 595–781, 1967.
 216. Maren, T. H. Current status of membrane‐bound carbonic anhydrase. Ann. N.Y. Acad. Sci. 341: 246–258, 1980.
 217. Maren, T. H., and A. C. Ellison. A study of renal carbonic anhydrase. Mol. Pharmacol. 3: 503–508, 1967.
 218. Maren, T. H., C. S. Rayburn, and N. E. Liddell. Inhibition by anions of human red cell carbonic anhydrase B: physiological and biochemical implications. Science 191: 469–472, 1976.
 219. McKinley, D. N., and P. L. Whitney. Particulate carbonic anhydrase in homogenates of human kidney. Biochim. Biophys. Acta 445: 780–790, 1976.
 220. McKinney, T. D., and M. B. Burg. Bicarbonate transport by rabbit cortical collecting tubules: effect of acid and alkali loads in vivo on transport in vitro. J. Clin. Invest. 60: 766–768, 1977.
 221. McKinney, T. D., and M. B. Burg. Bicarbonate and fluid absorption by renal proximal straight tubules. Kidney Int. 12: 1–8, 1977.
 222. McKinney, T. D., and M. B. Burg. Bicarbonate absorption by rabbit cortical collecting tubules in vitro. Am. J. Physiol. 234 (Renal Fluid Electrolyte Physiol. 3): F141–F145, 1978.
 223. McKinney, T. D., and M. B. Burg. Bicarbonate secretion by rabbit cortical collecting tubules in vitro. J. Clin. Invest. 61: 1421–1427, 1978.
 224. McKinney, T. D., and K. K. Davidson. Effects of potassium depletion (KD) on renal tubular water (Jv), bicarbonate (JtCO2) and chloride (JCl) absorption in rabbits. Clin. Res. 33: 587A, 1985 (abstr.).
 225. McKinney, T. D., and P. Myers. PTH inhibition of bicarbonate transport by proximal convoluted tubules. Am. J. Physiol. 239 (Renal Fluid Electrolyte Physiol. 8): F127–F134, 1980.
 226. McKinney, T. D., and P. Myers. Bicarbonate transport by proximal tubules: effect of parathyroid hormone and dibutyryl cyclic AMP. Am. J. Physiol. 238 (Renal Fluid Electrolyte Physiol. 7): F166–F174, 1980.
 227. McKinney, T. D., and P. Myers. Effect of calcium and phosphate on bicarbonate and fluid transport by proximal tubules in vitro. Kidney Int. 21: 433–438, 1982.
 228. DeMello‐Aires, M., and G. Malnic. Peritubular pH and Pco2 in renal tubular acidification. Am. J. Physiol. 228: 1766–1774, 1975.
 229. Mercier, O., M. Bichara, M. Paillard, and A. Prigent. Effects of parathyroid hormone and urinary phosphate on collecting duct hydrogen secretion. Am. J. Physiol. 251 (Renal Fluid Electrolyte Physiol. 20): F802–F809, 1986.
 230. Mercier, O., M. Bichara, M. Paillard, J. P. Gardin, and F. Leviel. Parathyroid hormone contributes to volume expansion‐induced inhibition of proximal reabsorption. Am. J. Physiol. 248 (Renal Fluid Electrolyte Physiol. 17): F100–F103, 1985.
 231. Mercier, O., A. Prigent, M. Bichara, M. Paillard, and F. Leviel. Effects of increase in plasma calcium concentration on renal handling of NaCl and NaHCO3. Am. J. Physiol. 250 (Renal Fluid Electrolyte Physiol. 19): F441–F450, 1986.
 232. Mishina, T., D. W. Scholer, and I. S. Edelman. Glucocorticoid receptors in rat kidney cortical tubules enriched in proximal and distal segments. Am. J. Physiol. 240 (Renal Fluid Electrolyte Physiol. 9): F38–F45, 1981.
 233. Moran, A., J. Biber, and H. Murer. A sodium‐hydrogen exchange system in isolated apical membrane from LLC‐PK1 epithelia. Am. J. Physiol. 251 (Renal Fluid Electrolyte Physiol. 20): F1003–F1008, 1986.
 234. Morel, F., D. Chabardes, and M. Imbert. Functional segmentation of the rabbit distal tubule by microdetermination of hormone‐dependent adenylate cyclase activity. Kidney Int. 9: 264–277, 1976.
 235. Murer, H., U. Hopfer, and R. Kinne. Sodium/proton antiport in brush‐border membrane vesicles isolated from rat small intestine and kidney. Biochem. J. 154: 597–604, 1976.
 236. Nakhoul, N. L., and W. F. Boron. Intracellular pH regulation in rabbit proximal straight tubules: basolateral transport. Kidney Int. 27: 286, 1985.
 237. Nakhoul, N. L., and W. F. Boron. Intracellular‐pH regulation in rabbit proximal straight tubules: dependence on external sodium. Federation Proc. 44: 1898, 1985 (abstr.).
 238. Nord, E. P., A. Hafezi, J. D. Kaunitz, W. Trizna, and L. G. Fine. pH gradient‐dependent increased Na+‐H+ antiport capacity of the rabbit remnant kidney. Am. J. Physiol. 249 (Renal Fluid Electrolyte Physiol. 18): F90–F98, 1985.
 239. Oberleithner, H. Intracellular pH in diluting segment of frog kidney. Pflugers Arch. 404: 244–251, 1985.
 240. Oliver, J. A., S. Himmelstein, and P. R. Steinmetz. Energy dependence of urinary bicarbonate secretion in turtle bladder. J. Clin. Invest. 55: 1003–1008, 1975.
 241. O'Neil, R. G., and S. I. Helman. Transport characteristics of renal collecting tubules: influences of DOCA and diet. Am. J. Physiol. 233 (Renal Fluid Electrolyte Physiol. 2): F544–F558, 1977.
 242. O'Regan, M. G., G. Malnic, and G. Giebisch. Cell pH and luminal acidification in Necturus proximal tubule. J. Membr. Biol. 69: 99–106, 1982.
 243. Pitts, R. F., and W. D. Lotspeich. Bicarbonate and the renal regulation of acid‐base balance. Am. J. Physiol. 147: 138–154, 1946.
 244. Pollack, A. S., D. G. Warnock, and G. J. Strewler. Parathyroid hormone inhibition of Na+‐H+ antiporter activity in a cultured renal cell line. Am. J. Physiol. 250 (Renal Fluid Electrolyte Physiol. 19): F217–F225, 1986.
 245. Preisig, P. A., H. E. Ives, E. J. Cragoe, Jr., R. J. Alpern, and F. C. Rector, Jr. The role of the sodium‐proton anti‐porter in rat proximal tubule bicarbonate absorption. J. Clin. Invest. 80: 970–978, 1987.
 246. Preisig, P. A., and R. J. Alpern. Chronic metabolic acidosis causes an adaptation in the apical membrane Na/H antiporter and basolateral membrane Na(HCO3)3 symporter in the rat proximal convoluted tubule. J. Clin. Invest. 82: 1445–1453, 1988.
 247. Preisig, P. A., and R. J. Alpern. Contributions of cellular leak pathways to net NaHCO3 and NaCl absorption. J. Clin. Invest. 83: 1859–1867, 1989.
 248. Preisig, P. A., and R. J. Alpern. Increased Na/H antiporter and Na/3HCO3 symporter activities in chronic hyperfiltration: a model of cell hypertrophy. J. Gen. Physiol. 97: 195–217, 1991.
 249. Pritchard, J. B., and J. L. Renfro. Renal sulfate transport at the basolateral membrane is mediated by anion exchange. Proc. Natl. Acad. Sci. USA 80: 2603–2607, 1983.
 250. Puschett, J. B., and P. Zurbach. Acute effects of parathyroid hormone on proximal bicarbonate transport in the dog. Kidney Int. 9: 501–510, 1976.
 251. Rector, F. C., Jr., N. W. Carter, and D. W. Seldin. The mechanism of bicarbonate reabsorption in the proximal and distal tubules of the kidney. J. Clin. Invest. 44: 278–290, 1965.
 252. Reenstra, W. W., D. G. Warnock, V. J. Yee, and J. G. Forte. Proton gradients in renal cortex brush border membrane vesicles: demonstration of a rheogenic proton flux with acridine orange. J. Biol. Chem. 256: 11663–11666, 1981.
 253. Rees‐Jones, R., and Q. Al‐Awqati. Proton‐translocating adenosinetriphosphatase in rough and smooth microsomes from rat liver. Biochemistry 23: 2236–2240, 1984.
 254. Richardson, R. M. A. Effect of acute hypercalcemia (HC) on renal HCO3 handling in the rat. Kidney Int. 23: 238, 1983 (abstr.).
 255. Richardson, R. M. A., and R. T. Kunau, Jr. Bicarbonate reabsorption in the papillary collecting duct: effect of acetazolamide. Am. J. Physiol. 243 (Renal Fluid Electrolyte Physiol. 12): F74–F80, 1982.
 256. Rodman, J. S., D. Kerjaschki, E. Merisko, and M. G. Farquahar. Presence of an extensive clathrin coat on the apical plasmalemma of the rat kidney proximal tubule cell. J. Cell Biol. 98: 1630–1636, 1984.
 257. Roos, A., and W. F. Boron. Intracellular pH. Physiol. Rev. 61: 296–434, 1981.
 258. Rosen, S. Localization of carbonic anhydrase activity in the vertebrate nephron. Histochem. J. 4: 35, 1972.
 259. Rubio, C. R., O. C. Mangili, G. B. DeMello, and G. Malnic. Effect of temperature on proximal tubular acidification. Pflugers Arch. 393: 71–76, 1982.
 260. Ruiz, O. S., J. A. L. Arruda, Z. Talor. Na‐HCO3 cotransport and Na‐H antiporter in chronic respiratory acidosis and alkalosis. Am. J. Physiol. 256 (Renal Fluid Electrolyte Physiol. 25): F414–F420, 1989.
 261. Sabolic, I., and G. Burckhardt. Proton pathways in rat renal brush‐border and basolateral membranes. Biochim. Biophys. Acta 734: 210–220, 1983.
 262. Sabolic, I., and G. Burckhardt. Effect of the preparation method on Na+‐H+ exchange and ion permeabilities in rat renal brush‐border membranes. Biochim. Biophys. Acta 772: 140–148, 1984.
 263. Sabolic, I., W. Haase, and G. Burckhardt. ATP‐dependent H+ pump in membrane vesicles from rat kidney cortex. Am. J. Physiol. 248 (Renal Fluid Electrolyte Physiol. 17): F835–F844, 1985.
 264. Sanyal, G., N. J. Pessah, and T. H. Maren. Kinetics and inhibition of membrane‐bound carbonic anhydrase from canine renal cortex. Biochim. Biophys. Acta 657: 128–137, 1981.
 265. Sasaki, S., and C. A. Berry. Mechanism of bicarbonate exit across basolateral membrane of the rabbit proximal convoluted tubule. Am. J. Physiol. 246 (Renal Fluid Electrolyte Physiol. 15): F889–F896, 1984.
 266. Sasaki, S., C. A. Berry, and F. C. Rector, Jr. Effect of luminal and peritubular concentrations and PCO2 on reabsorption in rabbit proximal convoluted tubules perfused in vitro. J. Clin. Invest. 70: 639–649, 1982.
 267. Sasaki, S., C. A. Berry, and F. C. Rector, Jr. Effect of potassium concentration on bicarbonate reabsorption in the rabbit proximal convoluted tubule. Am. J. Physiol. 224 (Renal Fluid Electrolyte Physiol. 13): F122–F128, 1983.
 268. Sasaki, S., Y. Iino, T. Shiigai, and J. Takeuchi. Intracellular pH of isolated perfused rabbit proximal tubule: effects of luminal Na and Cl. Kidney Int. 25: 282, 1984 (abstr.).
 269. Sasaki, S., T. Shiigai, and J. Takeuchi. Intracellular pH in the isolated perfused rabbit proximal straight tubule. Am. J. Physiol. 249 (Renal Fluid Electrolyte Physiol. 18): F417–F423, 1985.
 270. Sasaki, S., T. Shiigai, N. Yoshiyama, and J. Takeuchi. Mechanism of bicarbonate exit across basolateral membrane of rabbit proximal straight tubule. Am. J. Physiol. 252 (Renal Fluid Electrolyte Physiol. 21): F11–F18, 1987.
 271. Sasaki, S., and N. Yoshiyama. Interaction of chloride and bicarbonate transport across the basolateral membrane of rabbit proximal straight tubule. Evidence for sodium coupled chloride/bicarbonate exchange. J. Clin. Invest. 81: 1004–1011, 1988.
 272. Schild, L., L. P. Karniski, P. S. Aronson, and G. Giebisch. Formate stimulates active NaCl transport in the rabbit proximal tubule. Kidney Int. 29: 407, 1986 (abstr.).
 273. Schneider, D. L. ATP dependent acidification in intact and disrupted lysosomes: evidence for an ATP driven proton pump. J. Biol. Chem. 256: 3858–3864, 1981.
 274. Schultz, S. G. Homocellular regulatory mechanisms in sodium‐transporting epithelia: avoidance of extinction by “flush‐through.” Am. J. Physiol. 241 (Renal Fluid Electrolyte Physiol. 10): F579–F590, 1981.
 275. Schuster, V. L. Cyclic adenosine monophosphate‐stimulated bicarbonate secretion in rabbit cortical collecting tubules. J. Clin. Invest. 75: 2056–2064, 1985.
 276. Schuster, V. L., S. M. Bonsib, and M. L. Jennings. Two types of collecting duct mitochondria‐rich (intercalated) cells: lectin and band 3 cytochemistry. Am. J. Physiol. 251 (Cell Physiol. 20): C347–C355, 1986.
 277. Schwartz, G. J. Na +‐dependent H+ efflux from proximal tubule: evidence for reversible Na + ‐H+ exchange. Am. J. Physiol. 241 (Renal Fluid Electrolyte Physiol. 10): F380–F385, 1981.
 278. Schwartz, G. J. Absence of Cl−‐OH‐ or Cl−‐ exchange in the rabbit renal proximal tubule. Am. J. Physiol. 245 (Renal Fluid Electrolyte Physiol. 14): F462–F469, 1983.
 279. Schwartz, G. J., and Q. Al‐Awqati. Carbon dioxide causes exocytosis of vesicles containing H+ pumps in isolated perfused proximal and collecting tubules. J. Clin. Invest. 75: 1638–1644, 1985.
 280. Schwartz, G. J., J. Barasch, and Q. Al‐Awqati. Plasticity of functional epithelial polarity. Nature 318: 368–371, 1985.
 281. Schwartz, G. J., and M. B. Burg. Mineralocorticoid effects on cation transport by cortical collecting tubules in vitro. Am. J. Physiol. 235 (Renal Fluid Electrolyte Physiol. 4): F576–F585, 1978.
 282. Schwartz, G. J., A. M. Weinstein, R. E. Steele, J. L. Stephenson, and M. B. Burg. Carbon dioxide permeability of rabbit proximal convoluted tubules. Am. J. Physiol. 240 (Renal Fluid Electrolyte Physiol. 9): F231–F244, 1981.
 283. Schwartz, J. H., D. Bethencourt, and S. Rosen. Specialized function of carbonic anhydrase‐rich and granular cells of turtle bladder. Am. J. Physiol. 242 (Renal Fluid Electrolyte Physiol. 11): F627–F633, 1982.
 284. Schwartz, W. B., R. L. Jenson, and A. S. Relman. Acidification of the urine and increased ammonium excretion without change in acid‐base equilibrium: sodium reabsorption as a stimulus to the acidifying process. J. Clin. Invest. 34: 673680, 1955.
 285. Scoble, J. E., S. Mills, and K. A. Hruska. Calcium transport in canine renal basolateral membrane vesicles: effects of parathyroid hormones. J. Clin. Invest. 75: 1096–1105, 1985.
 286. Seely, J. F. Effects of peritubular oncotic pressure on rat proximal tubule electrical resistance. Kidney Int. 4: 28–35, 1973.
 287. Seifter, J. L., R. Knickelbein, and P. S. Aronson. Absence of Cl‐OH exchange and NaCl cotransport in rabbit renal microvillus membrane vesicles. Am. J. Physiol. 247 (Renal Fluid Electrolyte Physiol. 16): F753–F759, 1984.
 288. Shindo, T., and K. R. Spring. Chloride movement across the basolateral membrane of proximal tubule cells. J. Membr. Biol. 58: 35–42, 1981.
 289. Shiuan, D., and S. W. Weinstein. Evidence for electroneu‐tral chloride transport in rabbit renal cortical brush border membrane vesicles. Am. J. Physiol. 247 (Renal Fluid Electrolyte Physiol. 16): F837–F847, 1984.
 290. Silva, F., W. Schulz, L. Davis, X.‐S. Xie, and D. K. Stone. Immunocytochemical localization of the clathrin‐coated vesicle proton pump (CCV‐PP). Kidney Int. 31: 416, 1987 (abstr.).
 291. Silverman, D. N., and S. H. Vincent. Proton transfer in the catalytic mechanism of carbonic anhydrase. CRC Crit. Rev. Biochem. 14: 207–255, 1983.
 292. Soleimani, M., and P. S. Aronson. Effect of acetazolamide (ACTZ) on Na/HCO3 cotransport in renal basolateral membrane vesicles (BLMV). Kidney Int. 31: 416, 1987 (abstr.).
 293. Soleimani, M., and P. S. Aronson. Ionic mechanism of Na + ‐HCO3 cotransport in rabbit renal basolateral membrane vesicles. J. Biol. Chem. 264: 18302–18308, 1989.
 294. Soleimani, M., S. M. Grassl, and P. S. Aronson. Stoichiometry of Na+‐ cotransport in basolateral membrane vesicles isolated from rabbit renal cortex. Submitted.
 295. Soleimani, M., T. D. McKinney. Potassium depletion increases Na/H exchange and Na:CO3:HCO3 cotransport in rat renal cortex. Clin. Res. 37: 585a, 1989.
 296. Sonnenberg, H., and P. Deetjen. Methode zur Durchstromung einzelner Nephronabschnitte. Arch. Ges. Physiol. 279: 669–674, 1964.
 297. Spicer, S.S., M.A. Sens, and R. E. Tashian. Immunocytochemical determination of carbonic anhydrase in human epithelial cells. J. Histochem. Cytochem. 30: 864–873, 1982.
 298. Spicer, S. S., P. J. Stoward, and R. E. Tashian. The immunohistolocalization of carbonic anhydrase in rodent tissues. Histochem. Cytochem. 27: 820, 1979.
 299. Star, R. A. Quantitation of total carbon dioxide in nanoliter samples by flow‐through fluorometry. Am. J. Physiol. 258 (Renal Fluid Electrolyte Physiol. 27): F429–F432, 1990.
 300. Star, R. A., M. B. Burg, and M. A. Knepper. Bicarbonate secretion and chloride absorption by rabbit cortical collecting ducts: role of chloride/bicarbonate exchange. J. Clin. Invest. 76: 1123–1130, 1985.
 301. Star, R. A., M. B. Burg, and M. A. Knepper. Luminal disequilibrium pH and ammonia transport in outer medullary collecting duct. Am. J. Physiol. 252 (Renal Fluid Electrolyte Physiol. 21): F1148–F1157, 1987.
 302. Star, R. A., I. Kurtz, R. Mejia, M. B. Burg, and M. A. Knepper. Disequilibrium pH and ammonia transport in isolated perfused conical collecting ducts. Am. J. Physiol. 253 (Renal Fluid Electrolyte Physiol. 22): F1232–F1242, 1987.
 303. Steinmetz, P. R. Cellular mechanisms of urinary acidification. Physiol. Rev. 54: 890–956, 1974.
 304. Steinmetz, P. R., and L. R. Lawson. Effect of luminal pH on ion permeability and flows of Na+ and H+ in turtle bladder. Am. J. Physiol. 220: 1573–1580, 1971.
 305. Stetson, D. L., R. Beauwens, J. Palmisano, P. P. Mitchell, and P. R. Steinmetz. A double‐membrane model for urinary bicarbonate secretion. Am. J. Physiol. 249 (Renal Fluid Electrolyte Physiol. 18): F546–F552, 1985.
 306. Stetson, D. L., and P. R. Steinmetz. Role of membrane fusion in CO2 stimulation of proton secretion by turtle bladder. Am. J. Physiol. 245 (Cell Physiol. 14): Cl13–Cl20, 1983.
 307. Stetson, D. L., and P. R. Steinmetz. Alpha and beta types of carbonic anhydrase‐rich cells in turtle bladder. Am. J. Physiol. 249 (Renal Fluid Electrolyte Physiol. 18): F553–F565, 1985.
 308. Stetson, D. L., J. B. Wade, and G. Giebisch. Morphologic alterations in the rat medullary collecting duct following potassium depletion. Kidney Int. 17: 45–56, 1980.
 309. Stokes, J. B. Na and K transport across the cortical and outer medullary collecting tubule of the rabbit: evidence for diffusion across the outer medullary portion. Am. J. Physiol. 242 (Renal Fluid Electrolyte Physiol. 11): F514–F520, 1982.
 310. Stone, D. K., D. W. Seldin, J. P. Kokko, and H. R. Jacobson. Mineralocorticoid modulation of rabbit medullary collecting duct acidification: a sodium independent effect. J. Clin. Invest. 72: 77–83, 1983.
 311. Stone, D. K., D. W. Seldin, J. P. Kokko, and H. R. Jacobson. Anion dependence of rabbit medullary collecting duct acidification. J. Clin. Invest. 71: 1505–1508, 1983.
 312. Stone, D. K., X. S. Xie, and E. Racker. An ATP driven proton pump in clathrin‐coated vesicles. J. Biol. Chem. 258: 4059–4062, 1983.
 313. Stone, D. K., X. S. Xie, and E. Racker. Comparison of the proton ATPase and chloride transporter from bovine clathrin‐coated vesicles and renal medullary vesicles. Kidney Int. 25: 283, 1984 (abstr.).
 314. Struyvenberg, A., R. B. Morrison, and A. S. Relman. Acid‐base behavior of separated canine renal tubule cells. Am. J. Physiol. 214: 1155–1162, 1968.
 315. Talor, Z., J. Shuffield, G. Dytko, and J. A. L. Arruda. Chronic hypercapnia enhances the V‐max of Na‐H antiporter. Kidney Int. 27: 289, 1985 (abstr.).
 316. Tam, S. C., M. B. Goldstein, B. J. Stinebaugh, C. B. Chen, A. Gougoux, and M. L. Halperin. Studies on the regulation of hydrogen ion secretion in the collecting duct in vivo: evaluation of factors that influence the urine minus blood PCO2 difference. Kidney Int. 20: 636–642, 1981.
 317. Thomas, R. C. Intracellular pH of snail neurones measured with a new pH‐sensitive glass microelectrode. J. Physiol. (Lond.) 238: 159–180, 1974.
 318. Thomas, J. A., R. N. Buchsbaum, A. Zimniak, and E. Racker. Intracellular pH measurements in Ehrlich ascites tumor cells utilizing spectroscopic probes generated in situ. Biochemistry 18: 2210–2218, 1979.
 319. Thomas, J. A., P. C. Kolbeck, and T. A. Langworthy. Spectrophotometric determination of cytoplasmic and mitochondrial pH transients using trapped pH indicators. In: Intracellular pH: Its Measurement, Regulation, and Utilization in Cellular Functions, edited by R. Nuccitelli and D. W. Deamer. New York: Alan R. Liss, Inc., 1982, p. 105–123.
 320. Tsai, C.‐J., H. E. Ives, R. J. Alpern, V. J. Yee, D. G. Warnock, and F. C. Rector, Jr. Increased Vmax for Na+/H+ antiporter activity in proximal tubule brush border vesicles from rabbits with metabolic acidosis. Am. J. Physiol. 247 (Renal Fluid Electrolyte Physiol. 16): F339–F343, 1984.
 321. Ullrich, K. J., and F. Papavassiliou. Bicarbonate reabsorption in the papillary collecting duct of rats. Pflugers Arch. 389: 271–275, 1981.
 322. Ullrich, K. J., G. Rumrich, and K. Baumann. Renal proximal tubular buffer‐(glycodiazine) transport. Pflugers Arch. 357: 149–163, 1975.
 323. Verkman, A. S., and R. J. Alpern. Kinetic transport model for cellular regulation of pH and solute concentration in the renal proximal tubule. Biophys. J. 51: 533–546, 1987.
 324. Verkman, A. S., and H. E. Ives. Anomolous driving force for renal brush border H+/OH− transport characterized using 6‐carboxyfluorescein. Biochemistry 25: 2876–2882, 1986.
 325. Vieira, F. L., and G. Malnic. Hydrogen ion secretion by rat renal cortical tubules as studied by an antimony microelectrode. Am. J. Physiol. 214: 710–718, 1968.
 326. Vurek, G. G., D. G. Warnock, and R. Corsey. Measurement of picomole amounts of carbon dioxide by calorimetry. Anal. Chem. 47: 765–767, 1975.
 327. Wahlstrand, T., and P. J. Wistrand. Carbonic anhydrase C in the human renal medulla. Uppsala J. Med. Sci. 85: 7–17, 1980.
 328. Wang, W., G. Messner, H. Oberleithner, F. Lang, and P. Deetjen. The effect of ouabain on intracellular activities of K+, Na+, Cl−, H+, and Ca2+ in proximal tubules of frog kidneys. Pflugers Arch. 401: 6–13, 1984.
 329. Warnock, D. G., W. W. Reenstra, and V. J. Yee. Na+/H+ antiporter of brush border vesicles: studies with acridine orange uptake. Am. J. Physiol. 242 (Renal Fluid Electrolyte Physiol. 11): F733–F739, 1982.
 330. Warnock, D. G., and V. J. Yee. Chloride uptake by brush border membrane vesicles isolated from rabbit renal cortex: coupling to proton gradients and K+ diffusion potentials. J. Clin. Invest. 67: 103–115, 1981.
 331. Warnock, D. G., and V. J. Yee. Anion permeabilities of the isolated perfused rabbit proximal tubule. Am. J. Physiol. 242 (Renal Fluid Electrolyte Physiol. 11): F395–F405, 1982.
 332. Weiner, I. D., and L. L. Hamm. Regulation of intracellular pH in the rabbit cortical collecting tubule. J. Clin. Invest. 85: 274–281, 1990.
 333. Weinman, E. J., and M. Hise. cAMP‐protein kinase and Na+/H+ exchange in rabbit apical membrane vesicles. Kidney Int. 29: 378, 1986 (abstr.).
 334. Weinstein, A. M. Osmotic diuresis in a mathematical model of the rat proximal tubule. Am. J. Physiol. 250 (Renal Fluid Electrolyte Physiol. 19): F874–F884, 1986.
 335. Winne, D. Unstirred layer, source of biased Michaelis constant in membrane transport. Biochim. Biophys. Acta 298: 27–31, 1973.
 336. Wistrand, P. J. Renal membrane‐bound carbonic anhydrase: purification and properties. Uppsala J. Med. Sci. (Suppl.) 26: 75, 1979.
 337. Wistrand, P. J. Human renal cytoplasmic carbonic anhydrase: tissue levels and kinetic properties under near physiologic conditions. Acta Physiol. Scand. 109: 239–248, 1980.
 338. Wistrand, P. J., and R. Kinne. Carbonic anhydrase activity of isolated brush borders and basal‐lateral membranes of renal tubular cells. Pflugers Arch. 370: 121–126, 1977.
 339. Wistrand, P. J., and T. Walhstrand. Human renal carbonic anhydrases: purification and properties. Eur. J. Biochem. 57: 189–195, 1975.
 340. Wistrand, P. J., and T. Walhstrand. Rat renal and erythrocyte carbonic anhydrases: Purification and properties. Biochim. Biophys. Acta 481: 712–721, 1977.
 341. Wright, E. M., R. E. Schell, and R. D. Gunther. Proton and bicarbonate permeability of plasma membrane vesicles. In: Hydrogen Ion Transport in Epithelia, edited by J. G. Forte, D. G. Warnock, and F. C. Rector, Jr. New York: John Wiley and Sons, p. 21–33.
 342. Wright, F. S. Flow‐dependent transport processes: filtration, absorption, secretion. Am. J. Physiol. 243 (Renal Fluid Electrolyte Physiol. 12): F1–F11, 1982.
 343. Xie, X.‐S., and D. K. Stone. Isolation and reconstitution of the clathrin‐coated vesicle proton translocating complex. J. Biol. Chem. 261: 2492–2495, 1986.
 344. Yang, W. C., J. A. L. Arruda, and Z. Talor. Post‐hypercapnic metabolic alkalosis is mediated by increased Vmax of Na‐H antiporter. Clin. Res. 34: 703A, 1986 (abstr.).
 345. Yoshitomi, K., B.‐Ch. Burckhardt, and E. Fromter. Rheogenic sodium‐bicarbonate cotransport in the peritubular cell membrane of rat renal proximal tubule. Pflugers Arch. 405: 360–366, 1985.
 346. Yoshitomi, K., and E. Fromter. Cell pH of rat renal proximal tubule in vivo and the conductive nature of peritubular (OH−) exit. Pflugers Arch. 402: 300–305, 1984.
 347. Zeidel, M. L., P. Silva, and J. L. Seifter. Intracellular pH regulation in rabbit renal medullary collecting duct cells. Role of chloride‐bicarbonate exchange. J. Clin. Invest. 77: 1682–1688, 1986.
 348. Ziegler, T. W., D. D. Fanestil, and J. H. Ludens. Influence of transepithelial potential difference on acidification in the toad urinary bladder. Kidney Int. 10: 279–286, 1976.

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Renal Acidification: Cellular Mechanisms of Tubular Transport and Regulation
 

How to Cite

Robert J. Alpern, Floyd C. Rector. Renal Acidification: Cellular Mechanisms of Tubular Transport and Regulation. Compr Physiol 2011, Supplement 25: Handbook of Physiology, Renal Physiology: 767-812. First published in print 1992. doi: 10.1002/cphy.cp080118