Skip to main content
SpringerLink
Log in

Bicarbonate permeability of the outwardly rectifying anion channel

  • Articles
  • Published:
The Journal of Membrane Biology Aims and scope Submit manuscript

Summary

Single anion-selective channels have been studied in cultured human epithelial cells using the patch-clamp technique. Three cell types were used as models for different anion transport systems: (i) PANC-1, a cell line derived from the pancreatic duct, (ii) T84, a Cl-secreting colonic cell line, and (iii) primary cultures of sweat duct epithelium. Outwardly rectifying anion-selective channels were observed in all three preparations and were indistinguishable with respect to conductance, selectivity and gating. Striking similarities between HCO3- and Cl-secreting epithelia, and the high density of outward rectifiers in pancreatic cells prompted us to study HCO3 permeation through this channels. HCO3 permeability was significant when channels were bathed in symmetrical 150mm HCO3 solutions, Cl−HCO3 mixtures, and under bi-ionic conditions with outwardly and inwardly directed HCO3 gradients. Permeability ratios (P HCO3/P Cl) estimated from bi-ionic reversal potentials ranged from 0.50 to 0.64, although conductance ratios greater than 1.2 were observed with high extracellular pH. Chloride did not inhibit HCO3 permeation noticeably but rather had a small stimulatory effect when present on the opposite side of the membrane. The prevalence of outward rectifiers in PANC-1 and their permeability to bicarbonate suggests the channel may have a dual role in HCO3 secretion; to allow Cl recycling at the apical membrane and to mediate some of the HCO3 flux. Defective modulation of this channel in cystic fibrosis might provide a common basis for dysfunction in epithelia having very different anion transport properties (e.g., HCO3 secretion, Cl secretion and Cl absorption).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Almers, W., McClesky, E.W. 1984. The nonselective conductance in calcium channels of frog muscle: Calcium selectivity in a single-file pore.J. Physiol. (London) 353:585–608

    Google Scholar 

  2. Ashford, M.L.J. 1986. Single channel currents in cultured rat epididymal cells.J. Physiol. (London) 371:142P

    Google Scholar 

  3. Barry, P.H., Diamond, J.M. 1970. Junction potentials, electrode standard potentials, and other problems in interpreting electrical properties of membranes.J. Membrane Biol. 3:93–122

    Google Scholar 

  4. Bear, C.E. 1988. Phosphorylation-activated chloride channels in human skin fibroblasts.FEBS Lett. 237:145–149

    PubMed  Google Scholar 

  5. Bijman, J., Scholte, B., De Jonge, H.R. Hoogeveen, A.T., Kansen, M., Sinaasappel, M., Kamp, A.W.M. van der. 1988. Chloride transport in cystic fibrosis: Chloride channel regulation in cultured sweat duct and cultured nasal polyp epithelium.In: Cellular and Molecular Basis of Cystic Fibrosis. pp. 133–140. G. Mastella and P.M. Quinton, editors. San Francisco Press

  6. Booth, N.P., Brown, P.D., Donohue, M., Elliott, A.C., Lau, K.R., Pearce, R.J. 1988. The effects of DIDS and chloride-free solutions on the acidosis induced by acetylcholine in isolated acini from rabbit mandibular salivary gland.J. Physiol. (London) 403:44P

    Google Scholar 

  7. Bormann, J., Hamill, O.P., Sakmann, B. 1987. Mechanism of anion permeation through channels gated by glycine and γ-aminobutyric acid in mouse cultured spinal neurones.J. Physiol. (London) 385:243–286

    Google Scholar 

  8. Brodsky, W.A., Ehrenspeck, G., Durham, J. 1977. Some new aspects of anion pumping by the turtle bladder.Acta Physiol. Scand. (Suppl.):341–351

  9. Brown, P.D., Dho, S., Elliott, A.C., Lau, K.R. 1988. Acetylcholine causes a transient intracellular acidosis in isolated acini from rabbit mandibular gland.J. Physiol. (London) 396:171P

    Google Scholar 

  10. Butt, A.G., Worrell, R.T., Frizzell, R.A. 1988. A volume-sensitive epithelial chloride conductance.FASEB J. 2:A1284

    Google Scholar 

  11. Case, R.M., Holz, J., Hutson, D., Scratcherd, T., Wynne, R.D.A. 1979. Electrolyte secretion by the isolated cat pancreas during replacement of extracellular bicarbonate by organic anions and chloride by inorganic anions.J. Physiol. (London) 286:563–576

    Google Scholar 

  12. Case, R.M., Hunter, M., Novak, I., Young, J.A. 1984. The anionic basis of fluid secretion by the rabbit mandibular salivary gland.J. Physiol. (London) 349:619–630

    Google Scholar 

  13. Case, R.M., Scratcherd, T. 1970. On the permeability of the pancreatic duct membrane.Biochim. Biophys. Acta 219:493–495

    PubMed  Google Scholar 

  14. Collie, G., Buchwald, M., Harper, P., Riordan, J.R. 1985. Culture of sweat gland epithelial cells from normal individuals and patients with cystic fibrosis.In Vitro 21:597–602

    Google Scholar 

  15. Davis, B., Fisher, S., Krouse, M., Wine, J. 1988. Chloride channels in cultured human placental trophoblasts.Pediatr. Pulmonol. S2:99–100

    Google Scholar 

  16. Degnan, K.J., Karnaky, K.J., Zadunaisky, J.A. 1977. Active chloride transport in the in vitro opercular skin of a teleost (Fundulus heteroclitus), a gill-like epithelium rich in chloride cells.J. Physiol. (London) 271:155–191

    Google Scholar 

  17. Ehrenspeck, G. 1982. Effect of 3-isobutyl-1-methylxanthine on HCO −3 transport in turtle bladder. Evidence for electrogenic HCO −3 secretion.Biochim. Biophys. Acta 684:219–227

    PubMed  Google Scholar 

  18. Flemstrom, G. 1987. Gastric and duodenal mucosal bicarbonate secretion.In: Physiology of the Gastrointestinal Tract. (2nd ed.) L.R. Johnson, editor. Raven, New York

    Google Scholar 

  19. Flemstrom, G., Heylings, J.R., Garner, A. 1982. Gastric and duodenal HCO −3 transport in vitro: Effects of hormones and proposed local transmitters.Am. J. Physiol. 242:G100-G110

    PubMed  Google Scholar 

  20. Frizzell, R.A. 1987. Cystic fibrosis: A disease of ion channels?Trends Neurosci 10:190–193

    Google Scholar 

  21. Frizzell, R.A., Halm, D.R., Rechkemmer, G., Shoemaker, R.L. 1986. Chloride channel regulation in secretory epithelia.Fed. Proc. 45:2727–2731

    PubMed  Google Scholar 

  22. Frizzell, R.A., Rechkemmer, G., Shoemaker, R.L. 1986. Altered regulation of airway epithelial cell chloride channels in cystic fibrosis.Science 233:558–560

    PubMed  Google Scholar 

  23. Frizzell, R.A., Schultz, S.G. 1979. Sodium-coupled chloride transport by epithelial tissues.Am. J. Physiol. 236:F1-F8

    Google Scholar 

  24. Giraldez, F., Sepúlveda, F.V., Sheppard, D.N. 1988. An outward rectifying Cl−-selective channel in isolatedNecturus enterocytes.J. Physiol. (London) 407:102P

    Google Scholar 

  25. Gray, M.A., Greenwell, J.R., Argent, B.E. 1988. Ion channels in pancreatic duct cells: Characterization and role in bicarbonate secretion.In: Cellular and Molecular Basis of Cystic Fibrosis. G. Mastella and P.M. Quinton, editors. San Francisco Press

  26. Gray, M.A., Greenwell, J.R., Argent, B.E. 1988. Secretin-regulated chloride channel on the apical plasma membrane of pancreatic duct cells.J. Membrane Biol. 105:131–142

    Google Scholar 

  27. Greenwell, J.R. 1977. The selective permeability of the pacreatic duct of the cat to monovalent ions.Pfluegers Arch. 367:265–270

    Google Scholar 

  28. Gutknecht, J., Bisson, M.A., Tosteson, F.C. 1977. Diffusion of carbon dioxide through lipid bilayer membranes. Effects of carbonic anhydrase, bicarbonate, and unstirred layers.J. Gen. Physiol. 69:779–794

    PubMed  Google Scholar 

  29. Halm, D.R., Frizzell, R.A. 1988. Ion permeation through the apical membrane chloride channel in a secretory epithelial cell.FASEB J. 2:A1283

    Google Scholar 

  30. Halm, D.R., Rechkemmer, G., Shoumacher, R.A., Frizzell, R.A. 1987. Biophysical properties of an apical membrane chloride channel in a secretory epithelial cell line.Fed. Proc. 46:636

    Google Scholar 

  31. Halm, D.R., Rechkemmer, G., Shoumacher, R.A., Frizzell, R.A. 1988. Apical membrane chloride channels in a colonic cell line activated by secretory agonists.Am. J. Physiol. 254:C505-C511

    Google Scholar 

  32. Hamill, O.P., Marty, A., Neher, E., Sakmann, B., Sigworth, F.J. 1981. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches.Pfluegers Arch. 391:85–100

    Article  Google Scholar 

  33. Hanrahan, J.W., Alles, W., Lewis, S.A. 1985. Single anion-selective channels in basolateral membrane of a mammalian tight epithelium.Proc. Natl. Acad. Sci. USA 82:7791–7795

    PubMed  Google Scholar 

  34. Hayslett, J.P., Gögelein, H., Kunzelmann, K., Greger, R. 1987. Characteristics of apical chloride channels in human colon cells (HT29).Pfluegers Arch. 410:487–494

    Google Scholar 

  35. Hess, P., Tsien, R.W. 1984. Mechanism of ion permeation through calcium channels.Nature (London) 309:453–456

    Google Scholar 

  36. Hille, B. 1973. Potassium channels in myelinated nerve: Selective permeability to small cations.J. Gen. Physiol. 61:669–686

    Google Scholar 

  37. Kaila, K., Voipio, J. 1987. Postsynaptic fall in intracellular pH induced by GABA-activated bicarbonate conductance.Nature (London) 330:163–165

    Google Scholar 

  38. Klyce, S.D., Wong, R.K.S. 1977. Site and mode of adrenalin action on chloride transport across the rabbit corneal epithelium.J. Physiol. (London) 266:777–799

    Google Scholar 

  39. Kopelman, H., Corey, M., Gaskin, K., Durie, P., Weizman, Z., Forstner, G. 1988. Impaired chloride secretion, as well as bicarbonate secretion, underlies the fluid secretory defect in the cystic fibrosis pancreas.Gastroenterology 95:349–355

    PubMed  Google Scholar 

  40. Krnjević, K., Mitchell, J.F., Szerb, J.C. 1963. Determination of iontophoretic release of acetylcholine from micropipettes.J. Physiol. (London) 165:421–436

    Google Scholar 

  41. Li, M., McCann, J.D., Liedtke, C.M., Nairn, A.C., Greengard, P., Welsh, M.J. 1988. Cyclic AMP-dependent protein kinase opens chloride channels in normal but not cystic fibrosis airway epithelium.Nature (London) 331:358–360

    Google Scholar 

  42. Lieber, M., Mazzetta, J., Nelson-Rees, W., Kaplan, M., Todaro, G. 1975. Establishment of a continuous tumor-cell line (PANC-1) from a human carcinoma of the exocrine pancreas.Int. J. Cancer. 15:741–747

    PubMed  Google Scholar 

  43. Madden, M.E., Sarras, M.P., Jr. 1988. Morphological and biochemical characterization of a human pancreatic ductal cell line (PANC-1).Pancreas 3:512–528

    PubMed  Google Scholar 

  44. McCann, J.D., Welsh, M.J., Liedtke, C.M. 1987. Chloride channel currents in normal and cystic fibrosis airway epithelial cells.Fed. Proc. 46:1272 (abstr.).

    Google Scholar 

  45. Melvin, J.E., Moran, A., Turner, R.J. 1988. The role of HCO −3 and Na+/H+ exchange in the response of rat parotid acinar cells to muscarinic stimulation.J. Biol. Chem. 263:19564–19569

    PubMed  Google Scholar 

  46. Novak, I., Greger, R. 1988. Properties of the luminal membrane of isolated perfused rat pancreatic ducts. Effects of cyclic AMP and blockers of chloride transport.Pfluegers Arch. 411:546–553

    Google Scholar 

  47. Quinton, P.M. 1987. Physiology of sweat secretion.Kidney Int. 32:S102-S108

    Google Scholar 

  48. Reinhardt, R., Bridges, R.J., Rummel, W., Lindemann, B. 1987. Properties of an anion-selective channel from rat colonic enterocyte plasma membranes reconstituted into planar phospholipid bilayers.J. Membrane Biol. 95:47–54

    Google Scholar 

  49. Robinson, R.A., Stokes, R.H. 1965. Electrolyte Solutions. (2nd Ed.). Butterworths, London

    Google Scholar 

  50. Rothman, S.S., Brooks, F.P. 1965. Pancreatic secretion in vitro in “Cl-free”, “CO2-free”, and low Na+ environment.Am. J. Physiol. 209:790–796

    PubMed  Google Scholar 

  51. Saito, Y., Wright, E.M. 1983. Bicarbonate transport across the frog choroid plexus and its control by cyclic nucleotides.J. Physiol. (London) 336:635–648

    Google Scholar 

  52. Sataki, N., Durham, J.H., Ehrenspeck, G., Brodsky, W.A. 1983. Active electrogenic mechanisms for alkali and acid transport in turtle bladders.Am. J. Physiol. 244:C259-C269

    Google Scholar 

  53. Schoppa, N., Shorofsky, S.R., Jow, F., Fozzard, H., Nelson, D.J. 1988. Whole cell currents in cultured canine tracheal epithelial cells.Pediatr. Pulmonol. S2:101–102

    Google Scholar 

  54. Seow, F., Young, J.A. 1984. Anionic dependency of secretin-stimulated secretion by the isolated perfused rat pancreas.In: Secretion: Mechanism and Control. R.M. Case, J.M. Lingard, and J.A. Young, editors. pp. 97–102. Manchester University Press, Manchester

    Google Scholar 

  55. Shorofsky, S.R., Field, M., Fozzard, H.A. 1982. The cellular mechanism of active chloride secretion in vertebrate epithelia: Studies in intestine and trachea.Philos. Trans. R. Soc. London B299:597–607

    Google Scholar 

  56. Shoumacher, R.A., Shoemaker, R.L., Halm, D.R., Tallant, E.A., Wallace, R.W., Frizzell, R.A. 1987. Phosphorylation fails to activate chloride channels from cystic fibrosis airway cells.Nature (London) 330:752–754

    Google Scholar 

  57. Silva, P., Stoff, J., Field, M., Fine, L., Forrest, J., Epstein, F.H. 1977. Mechanisms of active chloride secretion by shark rectal gland: Role of Na-K-ATPase in chloride transport.Am. J. Physiol. 233:F298-F306

    Google Scholar 

  58. Simson, J.N.L., Merhav, A., Silen, W. 1981. Alkaline secretion by amphibian duodenum. III. Effects of dBcAMP, theophylline, and prostaglandins.Am. J. Physiol. 241:G529–536

    Google Scholar 

  59. Smith, P.L. 1985. Electrolyte transport by alkaline gland of little skateRaja erinacea.Am. J. Physiol. 248:R346-R352

    PubMed  Google Scholar 

  60. Stetson, D.L., Beauwens, R., Palmisano, J., Mitchell, P.P., Steinmetz, P.R. 1985. A double-membrane model for urinary bicarbonate secretion.Am. J. Physiol. 249:F546-F552

    Google Scholar 

  61. Stuenkel, E.L., Machen, T.E., Williams, J.A. 1988. pH regulatory mechanisms in rat pancreatic ductal cells.Am. J. Physiol. 254:G925-G930

    Google Scholar 

  62. Swanson, C.H., Solomon, A.K. 1973. A micropuncture investigation of the whole tissue mechanism of electrolyte secretion by the in vitro rabbit pancreas.J. Gen. Physiol. 62:407–429

    PubMed  Google Scholar 

  63. Swanson, C.H., Solomon, A.K. 1975. Micropuncture analysis of the cellular mechanisms of electrolyte secretion by the in vitro rabbit pancreas.J. Gen. Physiol. 65:22–45

    PubMed  Google Scholar 

  64. Weast, R.C. (editor) 1985. CRC Handbook of Chemistry and Physics. (66th Ed.) pp. D167-D168. CRC Press, Boca Raton (FL)

    Google Scholar 

  65. Welsh, M.J., Leidtke, C. 1986. Chioride and potassium channels in cystic fibrosis airway epithelia.Nature (London) 322:467–470

    Google Scholar 

  66. Welsh, M.J., Smith, P.L., Frizzell, R.A. 1983. Chloride secretion by canine tracheal epithelium: III. Membrane resistances and electromotive forces.J. Membrane Biol. 71:209–218

    Google Scholar 

  67. Yamamoto, D., Suzuki, N. 1987. Blockage of chloride channels by HEPES buffer.Proc. R. Soc. Lond. B230:93–100

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology, McGill University, H3G 1Y6, Montreal, Quebec, Canada

    J. A. Tabcharani & J. W. Hanrahan

  2. Department of Biochemistry, Hospital for Sick Children Research Institute and University of Toronto, M5G 1X8, Toronto, Ontario, Canada

    T. J. Jensen & J. R. Riordan

Authors
  1. J. A. Tabcharani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. J. Jensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. R. Riordan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. W. Hanrahan
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tabcharani, J.A., Jensen, T.J., Riordan, J.R. et al. Bicarbonate permeability of the outwardly rectifying anion channel. J. Membrain Biol. 112, 109–122 (1989). https://doi.org/10.1007/BF01871272

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01871272

Key Words

Search

Navigation