Skip to main content
SpringerLink
Log in

Influx mechanisms for Na+ and Cl− across the brush border membrane of leaky epithelia: A model and microelectrode study

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

Summary

This paper presents a numerical model for the movement of Na+, K+, Cl−, H+ and HCO −3 in a leaky epithelium. The model describes the active transport of Na+ and K+ at the serosal membrane and electrodiffusive permeation across the mucosal, serosal and junctional pathways. The model accounts for H+ and HCO −3 production in the cell. The influx of Na+ and Cl− is assumed to occur mainly via Na/H and Cl/HCO3 exchange. The behavior of the cell, with this influx mechanism, is compared to a cell with an obligatory neutral coupled influx of Na+ and Cl−. All parameters are obtained from the literature, primarily from studies utilizing theNecturus gallbladder. The analysis shows (i) that it is virtually impossible insteady-state experiments to distinguish between cells with Na/H−HCO3/Cl transport and cells with Na/Cl transport mechanisms. (ii) Thatnonsteady-state experiments can decide whether Na/H−HCO3/Cl or Na/Cl transport mechanisms mediate the influx of salt. A comparison between studies with ion-selective microelectrodes and the model predictions indicates that the influx of Na+ and Cl− is mediated by Na/H−HCO3/Cl transport when the external solutions contain CO2 and HCO3. (iii) The model also explains the diuretic effects of furosemide and carbonic anhydrase inhibitor, as well as the stimulatory effects on salt transport of elevated levels of HCO −3 at a constant pH. (iv) The model fails to explain some experiments performed in HCO3/CO2-free media and some experiments using inhibitors.

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

  • Alvarado, R.H., Dietz, T.H., Mullen, T.L. 1975. Chloride transport across isolated skin ofRana pipiens.Am. J. Physiol 229:869–876

    PubMed  Google Scholar 

  • Armstrong, W. McD., Bixenman, W.R., Frey, K.F., Garcia-Diaz, J.F., O'Regan, M.G., Owens, J.L. 1979. Energetics of coupled Na+ and Cl− entry into epithelial cells of bullfrog small intestine.Biochim. Biophys. Acta 551:207–219

    PubMed  Google Scholar 

  • Baerentsen, H.J., Christensen, O., Grove-Thomsen, P., Zeuthen, T. 1982. Steady states and the effects of ouabain in theNecturus gallbladder epithelium. A model analysis.J. Membrane Biol. (in press)

  • Boron, W.R., Russell, J.M., Brodwick, M.S. 1978. Influence of cyclic AMP on intracellular pH regulation and chloride fluxes in barnacle muscle fibres.Nature (London) 276:511–513

    Google Scholar 

  • Brazy, P.C., Gunn, R.B. 1976. Furosemide inhibition of chloride transport in human red blood cells.J. Gent Physiol. 68:583–599

    Article  Google Scholar 

  • Cook, D., Young, J.A. 1981. Computer simulation of salt and water transport in salivary ducts: Prediction of concentration profiles along the lumen of an epithelial tubule having both luminal and cellular compartments.In: Epithelial Ion and Water Transport. A.D.C. Macknight and J.P. Leader, editors. pp. 221–234. Raven Press, New York

    Google Scholar 

  • Cremaschi, D., Henin, S. 1975. Na+ and Cl− transepithelial routes in rabbit gallbladder.Pfluegers Arch. 361:33–41

    Article  Google Scholar 

  • Diamond, J.M. 1962. The reabsorptive function of the gallbladder.J. Physiol (London) 161:442–473

    Google Scholar 

  • Duffey, M.E., Thompson, S.M., Frizzell, R.A., Schultz, S.G. 1979. Intracellular chloride activities and active chloride absorption in the intestinal epithelium of the winter flounder.J. Membrane Biol. 50:331–341

    Article  Google Scholar 

  • Duffey, M.E., Turnheim, K., Frizzell, A., Schultz, S.G. 1978. Intracellular chloride activities in rabbit gallbladder: Direct evidence for the role of the sodium-gradient in energizing “uphill” chloride transport.J. Membrane Biol. 42:229–245

    Article  Google Scholar 

  • Ehrenspeck, G., Brodsky, W.A. 1976. Effects of 4-acetamido-4-isothiocyano-2,2-disulfonic stilbene on ion transport in turtle bladders.Biochim. Biophys. Acta 419:555–558

    PubMed  Google Scholar 

  • Ellory, J.C., Ramos, M., Zeuthen, T. 1978. Cl−-accumulation in plaice intestinal epithelium.J. Physiol. (London) 287:12–13

    Google Scholar 

  • Ericson, A.-C., Spring, K.R. 1982a. Coupled NaCl entry intoNecturus gallbladder epithelial cells.Am J. Physiol. 243:C140-C145

    PubMed  Google Scholar 

  • Ericson, A.-C., Spring, K.R. 1982b. Volume regulation byNecturus gallbladder: Apical Na+−H+ and Cl−−HCO −3 exchange.Am. J. Physiol. 243:C146-C150

    Google Scholar 

  • Field, M. 1978. Some speculations on the coupling between sodium and chloride transport processes in mammalian and teleost intestine.In: Membrane Transport Processes. J. Hoffmann, editor. Vol. 1, pp. 277–292. Raven Press, New York

    Google Scholar 

  • Fisher, R.S., Persson, B.E., Spring, K.R. 1981. Epithelial cell volume regulation: Bicarbonate dependence.Science 214:1357–1359

    PubMed  Google Scholar 

  • Frazier, L.W., Vanatta, J.C. 1971. Excretion of H+ and NH +4 by the urinary bladder of the acidotic toad and the effect of the short-circuit on the excretion.Biochim. Biophys. Acta 241:20–29

    PubMed  Google Scholar 

  • Frederiksen, O. 1973. Effect of amiloride on the transepithelial fluid transfer mechanism in rabbit gallbladderin vitro.Acta Physiol. Scand. Suppl. 396:103

    Google Scholar 

  • Frederiksen, O., Eldrup, E. 1981. Mechanism of coupled salt and water transfer across rabbit gallbladder epithelium.In: Water Transport Across Epithelia. H.H. Ussing, N. Bindslev, N.A. Lassen and O. Sten-Knudsen, editors. pp. 110–119. Munksgaard, Copenhagen

    Google Scholar 

  • Frizzell, R.A., Field, M., Schultz, S.G. 1979a. Sodiumcoupled chloride transport by epithelial tissues.Am. J. Physiol. 236:F1-F8

    Google Scholar 

  • Frizzell, R.A., Smith, P.L., Vosburgh, E., Field, M. 1979b. Coupled sodium-chloride influx across brush border of flounder intestine.J. Membrane Biol. 46:27–39

    Google Scholar 

  • Frömter, E., Ullrich, K.J. 1980. Effect of inhibitors and the mechanisms of anion transport in the proximal renal tubule of rats.Ann. N.Y. Acad. Sci. 341:97–110

    PubMed  Google Scholar 

  • Garcia-Diaz, J.F., Armstrong, W.McD. 1980. The steadystate relationship between sodium and chloride transmembrane electrochemical potential differences inNecturus gallbladder.J. Membrane Biol. 55:213–222

    Google Scholar 

  • Garcia-Romeu, F., Ehrenfeld, J. 1975. Chloride transport through the non short-circuited isolated skin ofRana esculenta.Am. J. Physiol. 228:845–849

    PubMed  Google Scholar 

  • Giraldez, F. 1982. Transients of intracellular ionic activities after mucosal Na replacement inNecturus gallbladder epithelium.Physiol. Soc. (in press)

  • Graf, J., Giebisch, G. 1979. Intracellular sodium activity and sodium transport inNecturus gallbladder epithelium.J. Membrane Biol. 47:327–355

    Google Scholar 

  • Green, H.H., Steinmetz, P.R., Frazier, H.S. 1968. Evidence for hydrogen ion transport by the turtle bladder in the presence of ambient bicarbonate.J. Clin. Invest. 47:43a

    Google Scholar 

  • Hoffmann, E.K., Sjøholm, C., Simonsen, L.O. 1981. Anioncation co-transport and volume regulation in Ehrlich ascites tumor cells.J. Physiol. (London) 319:94–95

    Google Scholar 

  • Hunter, M.J.. 1977. Human erythrocyte anion permeabilities measured under conditions of net charge transfer.J. Physiol. (London) 268:35–49

    Google Scholar 

  • Khuri, R.N., Bogharian, K.K., Agulian, S.K. 1974. Intracellular bicarbonate in single cells ofNecturus kidney proximal tubule.Pfluegers Areh 249:295–299

    Google Scholar 

  • Kinsella, J.L., Aronson, P.S. 1980. Properties of the Na+−H+ exchanger in renal microvillus membrane vesicles.Am. J. Physiol. 238:F461-F469

    Google Scholar 

  • Kinsella, J.L., Aronson, P.S. 1981. Amiloride inhibition of the Na+−H+ exchanger in renal microvillus membrane vesicles.Am. J. Physiol. 241:F374-F379

    Google Scholar 

  • Liedtke, C.M., Hopfer, U. 1977. Anion transport in brush border membranes isolated from rat small intestine.Biochem. Biophys. Res. Commun. 76:579–585

    Google Scholar 

  • Liedtke, C.M., Hopfer, U. 1982a. Mechanisms of Cl− translocation across small intestinal brush-border membrane. I. Absence of Na+−Cl− cotransport.Am. J. Physiol. 242:G263-G271

    Google Scholar 

  • Liedtke, C.M., Hopfer, U. 1982b. Mechanism of Cl− translocation across intestinal brush-border membrane. II. Demonstration of Cl−−OH− exchange and Cl− conductance.Am. J. Physiol. 242:G272-G280

    Google Scholar 

  • Machen, T.E., Zeuthen, T. 1983. HCO −3 /CO2 stimulates Na+/H+ and Cl−/HCO −3 exchange in the mucosal membrane ofNecturus gallbladder epithelium.J. Physiol. (London) (in press)

  • Motais, R., Garcia-Romeu, F. 1972. Transport mechanisms in the teleostean gill and amphibian skin.Annu. Rev. Physiol. 34:141–176

    PubMed  Google Scholar 

  • Murer, H., Hopfer, U., Kinne, R. 1976. Sodium/proton antiport in brush-border-membrane vesicles isolated from rat small intestine and kidney.Biochem. J. 754:597–604

    Google Scholar 

  • Nellans, H.N., Frizzell, R.A., Schultz, S.G. 1973. Coupled sodium-chloride influx across the brush border of rabbit ileum.Am. J. Physiol. 225:467–475

    PubMed  Google Scholar 

  • Os, C.H. van, Slegers, J.F.G. 1975. The electrical potential profile of gallbladder epithelium.J. Membrane Biol. 24:341–363

    Google Scholar 

  • Persson, B.-E., Spring, K.R. 1982. Gallbladder epithelial cell hydraulic water permeability and volume regulation.J. Gen. Physiol. 79:481–505

    PubMed  Google Scholar 

  • Petersen, K.-U., Heintze, K. 1982. The double ion exchange model of NaCl influx into gallbladder cells: Butyrate uptake rates.In: Electrolyte and Water Transport across Gastrointestinal Epithelia. R. Case, A. Garner, L.A. Turnberg and J.A. Young, editors. pp. 209–214. Raven Press, New York

    Google Scholar 

  • Pitts, R.F. 1961. A comparison of the modes of action of certain diuretic agents.Prog. Cardiovasc. Dis. 3:537–562

    PubMed  Google Scholar 

  • Pitts, R.F., Ayer, J.L., Schiess, W.A. 1949. The renal regulation of acid-base balance in man. III. The reabsorption and excretion of bicarbonate.J. Clin. Invest. 28:35–44

    Google Scholar 

  • Ramos, M.M.P., Ellory, J.C. 1981. Na and Cl transport across the isolated anterior intestine of the plaicePleuronectes platessa.J. Exp. Biol. 90:123–142

    Google Scholar 

  • Reuss, L., Weinmann, S.A. 1979. Intracellular ionic activities and transmembrane electrochemical potential differences in gallbladder epithelium.J. Membrane Biol. 49:345–362

    Article  Google Scholar 

  • Roughton, F.J.W. 1964. Transport of oxygen and carbon dioxide.In: Handbook of Physiology. W.O. Fenn and H. Rahn, editors. Sect. 3, Vol. 1, pp. 813–845. American Physiological Society Washington, D.C.

    Google Scholar 

  • Sachs, G., Faller, L.D., Rabon, E. 1982. Proton-hydroxyl transport in gastric and intestinal epithelia.J. Membrane Biol. 64:123–135

    Google Scholar 

  • Spring, K.R., Hope, A., Persson, B.-E., 1981. Quantitative light microscopic studies of epithelial fluid transport.In: Water Transport Across Epithelia. Alfred Benzon Symposium. H.H. Ussing, N. Bindslev, N.A. Lassen and O. Sten-Knudsen, editors. pp. 190–200. Munksgaard, Copenhagen.

    Google Scholar 

  • Spring, K.R., Kimura, G. 1978. Chloride readsorption by renal proximal tubules ofNecturus.J. Membrane Biol. 38:233–254

    Article  Google Scholar 

  • Turnberg, L.A., Bieberdorf, F.A., Morowski, S.G., Fordtran, J.S. 1970. Interrelationship of chloride, bicarbonate, sodium and hydrogen transport in human ileum.J. Clin. Invest. 49:557–567

    PubMed  Google Scholar 

  • Ussing, H.H. 1982. Volume regulation of frog skin epithelium.Acta Physiol. Scand. 114:363–369

    PubMed  Google Scholar 

  • Weinman, S.A., Reuss, L. 1982. Na+−H+ exchange at the apical membrane ofNecturus gallbladder.J. Gen. Physiol. 80:299–321

    PubMed  Google Scholar 

  • White, J.F. 1980. Bicarbonate-dependent chloride absorption in small intestine: Ion fluxes and intracellular chloride activities.J. Membrane Biol. 53:95–107

    Google Scholar 

  • Whitlock, R.T., Wheeler, H.O. 1969. Hydrogen ion transport by isolated rabbit gallbladder.Am. J. Physiol. 217:310–316

    Google Scholar 

  • Wieth, J.P., Brahm, J. 1982. Cellular anion exchange.In: Physiology and Pathology of Electrolyte Metabolism. G. Giebisch and D.W. Selding, editors. Raven Press, New York (in press)

    Google Scholar 

  • Wright, E.M. 1977. Effect of bicarbonate and other buffers on choroid plexus Na+/K+ pump.Biochim. Biophys. Acta 468:486–489

    PubMed  Google Scholar 

  • Zeuthen, T. 1978. Intra- and extracellular pH of absorptive epithelia measured with microelectrodes.Gastroenterologie, Clin. Biol. 2:334

    Google Scholar 

  • Zeuthen, T. 1980. How to make and use double-barrelled ion-selective microelectrodes.Curr. Top. Membr. Transp. 13:31–47

    Google Scholar 

  • Zeuthen, T. 1982. Relations between intracellular ion activities and extracellular osmolarity inNecturus gallbladder epithelium.J. Membrane Biol. 66:109–121

    Google Scholar 

  • Zeuthen, T., Ramos, M., Ellory, J.C. 1978. Inhibition of active chloride transport by piretanide.Nature (London) 273:678–680

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Medical Physiology A, The Panum Institute, University of Copenhagen, DK-2200, Copenhagen N, Denmark

    H. Baerentsen & T. Zeuthen

  2. The Physiological Laboratory, Cambridge, England

    F. Giraldez

Authors
  1. H. Baerentsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. Giraldez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T. Zeuthen
    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

Baerentsen, H., Giraldez, F. & Zeuthen, T. Influx mechanisms for Na+ and Cl− across the brush border membrane of leaky epithelia: A model and microelectrode study. J. Membrain Biol. 75, 205–218 (1983). https://doi.org/10.1007/BF01871951

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01871951

Key Words

Search

Navigation