The Use of Ion-Selective Microelectrodes to Study Cellular Transport Processes

  • J. Fernando García-Díaz
  • Fernando Giráldez


Ionic gradients and fluxes are involved in a number of cellular functions including nerve and muscle excitation and transepithelial absorption and secretion. It is of critical importance in these cases to obtain accurate measurements of intracellular ionic activities both at rest and during cell activation. Since the miniaturization of ion-selective glass membranes between 1950 and 1970, ion-selective microelectrodes (ISMs) have been extensively used for this purpose. The method allows not only measurement of steady-state values but also the monitoring of transient intracellular ionic activities. With certain provisos, the estimation of net transmembrane fluxes of ions is also possible. Improvement in the procedures for constructing ISMs and the introduction of liquid membranes (Walker, 1971) have allowed the technique to be used not only in large cells, typically of invertebrates, but also in smaller cells such as smooth muscle fibers, vertebrate neurons or tubular epithelia of the kidney.


Liquid Membrane Frog Skin Neutral Carrier Intracellular Measurement Microelectrode Amplifier 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Alvarez-Leefmans, F.J., Camino, S.M., Giraldez, F. and Nogueron, I., 1988. Intracellular chloride regulation in amphibian dorsal root ganglion neurones studied with ion-selective micro-electrodes. J Physiol.(London) 406: 225–246.Google Scholar
  2. Ammann, D., 1986. Ion-selective microelectrodes. Principles, design and application. Springer-Verlag, Berlin.Google Scholar
  3. Armstrong, W.McD. and Garcia-Diaz, J.F., 1980. Ion-selective microelectrodes: theory and technique. Federation Proc.: 39: 2851–2859.Google Scholar
  4. Armstrong, W.McD. and Garcia-Diaz, J.F., 1981. Criteria for the use of microelectrodes to measure membrane potentials in epithelial cells. In Epithelial Ion and Water Transport ( A.D.C. Macknight and J.P. Leader, eds.), pp. 43–53. Raven Press, New York.Google Scholar
  5. Bockris, J.0’M. and Reddy, A.K.N., 1973. Modern Electrochemistry. Vol. 1. Plenum/Rosetta Edition. Plenum Press. New York.Google Scholar
  6. Bolton,T.B. and Vaughan-Jones, R.D., 1977. Continuous direct measurement of intracellular chloride and pH in frog skeletal muscle. J. Physiol.(London) 270: 801–833.Google Scholar
  7. Brown, K.T. and Flaming, D.G., 1977. New microelectrodes techniques for intracellular work in small cells. Neuroscience 2: 813–827.CrossRefGoogle Scholar
  8. Coles, J.A. and Tsacopoulos, M., 1977. A method of making fine double-barrelled potassium-sensitive micro-electrodes for intracellular recording. J. Physiol.(London) 270: 12P - 14 P.Google Scholar
  9. Coles, J.A. and Tsacopoulos, M., 1979. Potassium activity in photoreceptors, glial cells and extracellular space in the drone retina: changes during photostimulation. J. Physiol (London) 290: 525–549.Google Scholar
  10. Conway, B.E., 1952. Electrochemical data. Elsevier, Amsterdam.Google Scholar
  11. Edelman, A., Curet, S., Samarzija, I. and Frömter, E., 1978. Determination of intracellular K activity in rat kidney proximal tubular cells. Pflügers Arch. 378: 37–45.PubMedCrossRefGoogle Scholar
  12. Eisenman, G., 1967. Glass Electrodes For Hydrogen and Other Cations. Principles and Practice. M. Dekker, Inc.. New York.Google Scholar
  13. Eisenman, G., 1968. Similarities and differences between liquid and solid ion exchangers and their usefulness as ion specific electrodes. Anal. Chem. 40: 310–320.CrossRefGoogle Scholar
  14. Eisner, D.A., Lederer, W.J. and Vaughan-Jones, R.D., 1981. The dependence of Na pumping and tension on intracellular sodium activity in voltage-clamped sheep Purkinje fibres. J. Physiol.(London) 317: 163–187.Google Scholar
  15. Garcia-Diaz, J.F., Baxendale, L.M., Klemperer, G. and Essig, A., 1985. Cell K activity in frog skin in the presence and absence of cell current. J. Membrane Biol. 85: 143–158.CrossRefGoogle Scholar
  16. Garcia-Diaz, J.F. and Essig, A., 1985. Capacitative transients in voltage-clamped epithelia. Biophys. J. 48: 519–523.PubMedCrossRefGoogle Scholar
  17. Garcia-Diaz, J.F., Klemperer, G., Baxendale, L.M. and Essig, A., 1986. Cell sodium activity and sodium pump function in frog skin. J. Membrane Biol. 92: 37–46.CrossRefGoogle Scholar
  18. Garcia-Diaz, J.F., Stump, S. and Armstrong, W.McD., 1984. Electronic device for microelectrode recordings in epithelial cells. Am. J. Physiol. 246: C339 - C346.PubMedGoogle Scholar
  19. Giraldez, F., 1984. Active sodium transport and fluid secretion in the gall-bladder epithelium of Necturus. J. Physiol.(London) 348: 431–455.Google Scholar
  20. Giraldez, F. and Sepulveda, F.V., 1986. Chloride activity in Necturus enterocytes. J. Physiol.(London) 380: 26 P.Google Scholar
  21. Gorman, A.L.F., Levy, S., Nasi, E. and Tillotson, D., 1984. Intracellular calcium measured with calcium-sensitive micro-electrodes and arsenazo III in voltage-clamped Aplysía neurones. J. Physiol.(London) 353: 127–142.Google Scholar
  22. Guibault, G.C., Durst, R.A., Frant, M.S., Freiser, H., Hansen, E.H., Light, T.S., Pungor, E., Rechnitz, G., Rice, N.M., Rohm, T.J., Simon, W. and Thomas, J.D.R., 1976. Recommendations for nomenclature of ion-selective electrodes. Pure Appl. Chem. 48: 127–132.CrossRefGoogle Scholar
  23. Halliwell, J.V. and Whitaker,M.J., 1987. Using microelectrodes. In Microelectrodes Techniques: The Plymouth Workshop Handbook ( N.B. Standen, P.T.A. Gray and M.J. Whitaker, eds.), pp. 1–12. The Company of Biologists Ltd., Cambridge.Google Scholar
  24. Horowitz, P. and Hill, W., 1989. The Art of Electronics. Cambridge University Press, Cambridge.Google Scholar
  25. Hu, Z., Buhrer, T., Muller, M., Rusterholtz, B., Rouilly, M. and Simon, W., 1989. Intracellular magnesium ion selective microelectrode based on a neutral carrier. Anal Chem. 61: 574–576.PubMedCrossRefGoogle Scholar
  26. IUPAC, 1979. Commission on analytical nomenclature (prepared for publication by G.C. Guibault). Recommendations for publishing manuscripts on ion-selective electrodes. Ion-selective Electrode Rev, 1: 139.Google Scholar
  27. Koryta, J. and Stulik, K., 1983. Ion-Selective Electrodes. Second Edition. Cambridge University Press. Cambridge.CrossRefGoogle Scholar
  28. Lanter, F., Steiner, R.A., Ammann, D. and Simon, W. 1982. Critical evaluation of the applicability of neutral carrier based Cat+ selective microelectrodes. Anal. Chim. Acta 135: 51–59.CrossRefGoogle Scholar
  29. Lev, A.A. and Armstrong, W.McD., 1975. Ionic activities in cells. Curr Top. Membranes and Transp. 6: 59–123.CrossRefGoogle Scholar
  30. Levy, S. and Fein, A., 1985. Relationship between light sensitivity and intracellular free Ca concentration in Límulus ventral photoreceptors: a quantitative study using Ca-selective microelectrodes. J. Gen. Physiol. 85: 805–841.PubMedCrossRefGoogle Scholar
  31. Morris, M.E. and Krnjevic, K. (editors), 1987. Ion-Selective Microelectrodes and Excitable Tissues. Can. J. Physiol. Pharmacol, 65: 867–1100.Google Scholar
  32. Moody, G.J. and Thomas, J.D.R., 1971. Selective ion-sensitive electrodes. Merrow Pub.Co.Ltd., Watford, England.Google Scholar
  33. Munoz, J.L., Deyhimi, F. and Coles, J.A., 1983. Silanization of glass in the making of ion-sensitive microelectrodes. J. Neurosci. Meth. 8: 231–247.CrossRefGoogle Scholar
  34. Nelson, D.J., Ehrenfel, J. and Lindemann, B., 1978. Volume changes and potential artifacts of epithelial cells of frog skin following impalement with microelectrodes filled with 3M KC1. J. Membrane Biol. 40 (Special Issue): 91–119.CrossRefGoogle Scholar
  35. O’Doherty, J., Garcia-Diaz, J.F. and Armstrong, W.McD., 1979. Sodium-selective liquid ion-exchanger microelectrodes for intracellular measurements. Science 203: 1349–1351.PubMedCrossRefGoogle Scholar
  36. Ogden,D.C., 1987. Microelectrode electronics. In Microelectrodes Techniques: The Plymouth Workshop Handbook ( N.B. Standen, P.T.A. Gray and M.J. Whitaker, eds.), pp. 199–227. The Company of Biologists Ltd., Cambridge.Google Scholar
  37. Parsons, R., 1959. Handbook of Electrochemical Constants. Butterworths Scientific Publications. London.Google Scholar
  38. Persson, B.-E. and Spring, K.R., 1982. Gallbladder epithelial cell hydraulic water permeability and volume regulation. J.Gen.Physiol. 79: 481–505.PubMedCrossRefGoogle Scholar
  39. Purves, R.D., 1981. Microelectrode methods for intracellular recording and ionophoresis. Academic Press, London.Google Scholar
  40. Reuss,L., 1985. Changes in cell volume measured with an electrophysiologic technique. Proc. Natl. Acad. Sci. 82: 6014–6018.CrossRefGoogle Scholar
  41. Robinson, R.A. and Stokes, R.H., 1959. Electrolyte Solutions. Second Edition (revised). Butterworths Scientific Publications. London.Google Scholar
  42. Roos, A. and Boron, W.F., 1981. Intracellular pH. Physiol. Rev. 61: 296–434.PubMedGoogle Scholar
  43. Schefer, U., Ammann, D., Pretsch, E., Oesch, U. and Simon, W., 1986. Neutral carrier based Ca-selective electrode with detection limit in the sub-nanomolar range. Anal.Chem. 58: 2282–2285.CrossRefGoogle Scholar
  44. Thomas, M.V., 1982. Techniques in calcium research. Academic Press, London.Google Scholar
  45. Thomas, R.C., 1972. Intracellular sodium activity and the sodium pump in snail neurones. J. Physiol.(London) 220: 55–71.Google Scholar
  46. Thomas, R.C., 1978. Ion-sensitive intracellular microelectrodes. How to make and use them. Academic Press, London.Google Scholar
  47. Tripathi, S., Morgunov, N. and Boulpaep, E.L., 1985. Submicron tip breakage and silanization control improve ion-selective microelectrodes. Am. J. Physiol. 249: C514–0521.PubMedGoogle Scholar
  48. Tsien, R.Y., 1980. Liquid sensors for ion-selective microelectrodes. TINS 3.:219–221.Google Scholar
  49. Tsien, R.Y., 1983. Intracellular measurements of ion activities. Ann. Rev, Biophys. Bioeng. 12: 91–116.CrossRefGoogle Scholar
  50. Tsien, R.Y. and Rink, T.J., 1980. Neutral carrier ion-selective microelectrodes for measurement of intracellular free calcium. Biochim. Biophys. Acta 599: 623–638.PubMedCrossRefGoogle Scholar
  51. Tsien, R.Y. and Rink, T.J., 1981. Ca-selective electrodes: A novel PVC-gelled neutral carrier mixture compared with other currently available sensors. J.Neurosci.Meth. 4: 73–86.CrossRefGoogle Scholar
  52. Vaughan-Jones, R.D., 1979. Non-passive chloride distribution in mammalian heart muscle: microelectrode measurement of the intracellular chloride activity. J. Physiol.(London) 295: 83–109.Google Scholar
  53. Vaughan-Jones, R.D. and Aickin, C.C., 1987. Ion-selective microelectrodes, In Microelectrode Techniques: The Plymouth Workshop Handbook. (N.B, Standen, P.T.A. Gray and M.J. Whitaker, eds.), pp. 137–167. The Company of Biologists Ltd., Cambridge.Google Scholar
  54. Walker, J.L.,Jr., 1971. Ion specific liquid ion exchanger microelectrodes. Anal.Chem. 43: 89A - 93A.Google Scholar
  55. Zeuthen, T., 1980. How to make and use double-barrelled ion-selective microelectrodes. Curr Top. Membranes and Transp. 13: 31–47.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • J. Fernando García-Díaz
    • 1
    • 2
  • Fernando Giráldez
    • 1
    • 2
  1. 1.Department of PhysiologyBoston University School of MedicineBostonUSA
  2. 2.Departamento de Bioquímica y Biología Molecular y FisiologíaUniversidad de ValladolidValladolidSpain

Personalised recommendations