Pflügers Archiv

, Volume 427, Issue 1–2, pp 143–150 | Cite as

An electrophysiological study of angiotensin II regulation of Na-HCO3 cotransport and K conductance in renal proximal tubules

I. Effect of picomolar concentrations
  • Salvatore Coppola
  • Eberhard Frömter
Transport Processes, Metabolism and Endocrinology; Kidney, Gastrointestinal Tract, and Exocrine Glands


The effect of picomolar concentrations of angiotensin II (AII) was investigated in isolated perfused rabbit renal proximal tubules using conventional or pH-sensitive intracellular microelectrodes. Under control conditions cell membrane potential (Vb) and cell pH (pHi) averaged −53.8±1.9 mV (mean±SEM,n=49) and 7.24±0.01 (n=10), respectively. AII (at 10−11 mol/l), when applied from the bath (but not when applied from the lumen perfusate), produced the following effects: approximately 85% of the viable tubules responded with a small depolarization (+ 5.5±0.4 mV,n=43) which was accompanied in half of the pHi measurements by a slow acidification (ΔpHi=−0.03±0.01,n=5). The remaining 15% responded with a small hyperpolarization (ΔVb=−3.1±0.4 mV,n=6). All changes were fully reversible and repeatable. Experiments with fast changes in bath HCO3 or K concentrations, as well as measurements of the basolateral voltage divider fraction in response to transepithelial current flow, explain these observations as stimulation of a basolateral Na-HCO3 cotransporter and of a basolateral K conductance. Both counteract in their effect onVb, but can be individuated by blocker experiments with 4,4′-diisothiocyanatostilbene-2,2′-disulphonic acid (DIDS) and barium. Both the stimulation of Na-HCO3 cotransport and the stimulation of the K conductance may result from down-regulation of the level of cyclic adenosine monophosphate in the cell.

Key words

Rabbit renal proximal tubule Angiotensin II Cell potential Cell pH Na-HCO3 cotransport K conductance 


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  1. 1.
    Biagi BA, Sothell M (1986) pH sensitivity of the basolateral membrane of the rabbit proximal tubule. Am J Physiol 250:F 261-F 266Google Scholar
  2. 2.
    Burg G, Grantham J, Abramow M, Orloff J (1966) Preparation and study of fragments of single rabbit nephrons. Am J Physiol 210:1293–1298Google Scholar
  3. 3.
    Cook DI, Frömter E (1985) Is the voltage divider ratio a reliable estimate of the resistance ratio of the cell membranes in tubular epithelia. Pflügers Arch 403:388–395Google Scholar
  4. 4.
    Coppola S, Frömter E (1994) An electrophysiological study of angiotensin II regulation of Na-HCO3 cotransport and K conductance in renal proximal tubules. II. Effect of micromolar concentrations. Pflügers Arch 427:151–156Google Scholar
  5. 5.
    Douglas JG (1987) Angiotensin receptor subtypes of the kidney cortex. Am J Physiol 253:F 1-F 7Google Scholar
  6. 6.
    Endou H, Jung KY, Ota R, Tojo A (1991) Angiotensin II receptor subtypes in rat early proximal tubule. Contrib Nephrol 95:190–196Google Scholar
  7. 7.
    Geibel J, Giebisch G, Boron WF (1990) Angiotensin II stimulates both Na-H exchange and Na-HCO3 cotransport in the rabbit proximal tubule. Proc Natl Acad Sci USA 87:7917–7920Google Scholar
  8. 8.
    Gögelein H (1990) Ion channels in mammalian proximal renal tubules. Renal Physiol Biochem 13:8–25Google Scholar
  9. 9.
    Harris PJ, Young JA (1977) Dose-dependent stimulation and inhibition of proximal tubular sodium reabsorption by angiotensin II in the rat kidney. Pflügers Arch 367:295–297Google Scholar
  10. 10.
    Kondo Y, Frömter E (1987) Axial heterogeneity of sodium-bicarbonate cotransport in proximal straight tubule of rabbit kidney. Pflügers Arch 410:481–486Google Scholar
  11. 11.
    Kondo Y, Bührer T, Seiler K, Frömter E, Simon W (1989) A new double-barelled ionophore-based microelectrode for chloride ions. Pflügers Arch 414:663–668Google Scholar
  12. 12.
    Lang F, Rehwald W (1992) Potassium channels in renal epithelial transport regulation. Physiol Rev 72:1–72Google Scholar
  13. 13.
    Liu FY, Cogan MG (1987) Angiotensin II: a potent regulator of acidification in the rat early proximal convoluted tubule. J Clin Invest 80:272–275Google Scholar
  14. 14.
    Liu FY, Cogan MG (1988) Angiotensin II stimulation of hydrogen ion secretion in the rat early proximal tubules. Modes of action, mechanism and kinetics. J Clin Invest 82:601–607Google Scholar
  15. 15.
    Liu FY, Cogan MG (1989) Angiotensin II stimulates early proximal bicarbonate absorption in the rat by decreasing cyclic adenosine monophosphate. J Clin Invest 84:83–91Google Scholar
  16. 16.
    Payett DM, Dupuis G (1992) Dual regulation of the n type K channel in Jurkat T lymphocytes by protein kinase A and C. J Biol Chem 267:18 270–18 273Google Scholar
  17. 17.
    Romero AM, Hopfer U, Madhun ZT, Zhan W, Douglas JG (1991) Angiotensin II actions in the rabbit proximal tubule. Renal Physiol Biochem 14:199–207Google Scholar
  18. 18.
    Ruiz OS, Arruda JAL (1992) Regulation of the renal NaHCO3 cotransporter by cAMP and Ca-dependent protein kinases. Am J Physiol 262:F 560-F 565Google Scholar
  19. 19.
    Schuster VL, Kokko JP, Jacobson HR (1984) Angiotensin II directly stimulates transport in rabbit proximal convoluted tubules. J Clin Invest 73:507–515Google Scholar
  20. 20.
    Seki G, Frömter E (1992) Acetazolamide inhibition of basolateral base exit in rabbit renal proximal tubule S2 segment. Pflügers Arch 422:60–65Google Scholar
  21. 21.
    Seki G, Coppola S, Frömter E (1993) The Na-HCO3 cotransporter operates with a coupling ratio of 2 HCO3 to 1 Na in isolated rabbit renal proximal tubule. Pflügers Arch 425:409–416Google Scholar
  22. 22.
    Tsuchiya K, Wang W, Giebisch G, Welling PA (1992) ATP is a coupling modulator of parallel, Na,K-ATPase-K-channel activity in the renal proximal tubule. Proc Natl Acad Sci USA 89:6418–6422Google Scholar
  23. 23.
    Wang W, Giebisch G (1991) Dual modulation of renal ATP-sensitive K channel by protein kinases A and C. Proc Natl Acad Sci USA 88:9722–9725Google Scholar
  24. 24.
    Wang W, Sackin H, Giebisch G (1992) Renal potassium channels and their regulation. Annu Rev Physiol 54:81–96Google Scholar
  25. 25.
    Woodcock EA, Johnston CI (1982) Inhibition of adenylate cyclase by angiotensin II in rat renal cortex. Endocrinology 111:1687–1691Google Scholar
  26. 26.
    Yatani A, Codina J, Brown AM, Birnbaumer L (1987) Direct activation of mammalian atrial muscarinic potassium channels by GTP regulatory protein Gk. Science 235:207–211Google Scholar

Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • Salvatore Coppola
    • 1
  • Eberhard Frömter
    • 1
  1. 1.Zentrum der PhysiologieKlinikum der Johann Wolfgang Goethe-UniversitätFrankfurt/MainGermany

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