The Journal of Membrane Biology

, Volume 25, Issue 1, pp 311–326 | Cite as

Effect of local anesthetics on chloride transport in erythrocytes

  • R. B. Gunn
  • J. A. CooperJr.
Article

Summary

The self-exchange of chloride isotopes across the human erythrocyte membrane was inhibited by tetracaine, benzocaine, and lidocaine. The inhibition by tetracaine was increased at higher pH values, but was not exclusively due to the uncharged form of tetracaine. The inhibition was effective within 5 seconds, was reversible, was noncompetitive with chloride ions, and was not reversed by calcium ions. These findings indicate that local anesthetics react with the erythrocyte chloride carrier at a site separate from the chloride site and cause inhibition of anion transport by a specific mechanism not involving changes in the surface charge density on the erythrocyte membrane.

Keywords

Chloride Charge Density Lidocaine Surface Charge Local Anesthetic 

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References

  1. 1.
    Andersen, N.B. 1968. The effect of local anesthetic and pH on sodium and potassium flux in human red cells.J. Pharmacol. Exp. Ther. 163:393PubMedGoogle Scholar
  2. 2.
    Århem, P., Frankenhaeuser, B. 1974. Local anesthetics: Effects on permeability properties of nodal membrane in myelinated nerve fibres fromXenopus. Potential clamp experiments.Acta Physiol. Scand. 91:11PubMedGoogle Scholar
  3. 3.
    Blaustein, M.P., Goldman, D.E. 1966. Competitive action of calcium and procaine on lobster axon.J. Gen. Physiol. 49:1043PubMedGoogle Scholar
  4. 4.
    Burt, D.H., Green, J.W. 1971. The sodium permeability of butanol-treated erythrocytes; the role of calcium.Biochim. Biophys. Acta 225:46PubMedGoogle Scholar
  5. 5.
    Cabantchik, Z.I., Rothstein, A. 1974. Membrane proteins related to anion permeability of human red blood cells. I. Localization of disulfonic stilbene binding sites in proteins involved in permeation.J. Membrane Biol. 15:207Google Scholar
  6. 6.
    Cerbón, J. 1972. NMR evidence for the hydrophobic interaction of local anesthetics.Biochim. Biophys. Acta 290:51PubMedGoogle Scholar
  7. 7.
    Dalmark, M., Wieth, J.O. 1972. Temperature dependence of chloride, bromide, iodide, thiocyanate and salicylate transport in human red cells.J. Physiol. (London) 224:553Google Scholar
  8. 8.
    Deuticke, B., Gruber, W. 1970. Anion permeability of mammalian red blood cells: Possible relation to membrane phospholipid patterns.Biochim. Biophys. Acta 211:369Google Scholar
  9. 9.
    Eisenbrand, J., Picher, H. 1938. Bestimmung der Dissoziationskonstanten, Löslichkeiten und Verteilungskoeffizienten von Pantokain- und Novokainbase.Arch. Pharm. Ber. Dtsch. Pharm. Ges. 276:1Google Scholar
  10. 10.
    Funder, J., Wieth, J.O. 1967. Effect of ouabain on glucose metabolism and on fluxes of sodium and potassium of human blood cells.Acta Physiol. Scand. 71:113PubMedGoogle Scholar
  11. 11.
    Gunn, R.B. 1972. A titratable carrier model for both mono- and di-valent anion transport in human red blood cells.In: Oxygen Affinity of Hemoglobin and Red Cell Acid-Base Status. M. Rørth and P. Astrup, editors, p. 823. Munksgaard. CopenhagenGoogle Scholar
  12. 12.
    Gunn, R.B., Dalmark, M., Tosteson, D.C., Wieth, J.O. 1973. Characteristics of chloride transport in human red blood cells.J. Gen. Physiol. 61:185PubMedGoogle Scholar
  13. 13.
    Gunn, R.B., Wieth, J.O., Tosteson, D.C. 1975. Some effects of low pH on chloride exchange in human red blood cells.J. Gen. Physiol. 65:731PubMedGoogle Scholar
  14. 14.
    Hardy, C.A., Shah, D.O. 1972. Effect of local anesthetics on red blood cell surface charge.Int. Biophys. Congr., Moscow. (Abstr.)Google Scholar
  15. 15.
    Hauser, H., Penkett, S.A., Chapman, D. 1969. Nuclear magnetic resonance spectroscopic studies of procaine hydrochloride and tetracaine hydrochloride at lipid-water interfaces.Biochim. Biophys. Acta 183:466PubMedGoogle Scholar
  16. 16.
    Hille, B. 1966. Common mode of action of three agents that decrease the transient change in sodium permeability in nerves.Nature 210:1220PubMedGoogle Scholar
  17. 17.
    Lassen, U.V., Pape, L., Vestergaard-Bogind, B. 1973. Membrane potential of amphiuma red cells: Effect of calcium.In: Erythrocytes, Thrombocytes, Leukocytes. E. Garlach, K. Moser, E. Deutsch and W. Wilmanns, editors. p. 33. Georg Thieme Publishers, StuttgartGoogle Scholar
  18. 18.
    McLaughlin, S., Harary, H. 1975. The utility of the Stern equation in describing the adsorption of charged molecules to bilayer membranes.Biophys. J. 15:306aGoogle Scholar
  19. 19.
    Narahashi, T., Frazier, D.T., Moore, J.W. 1972. Comparison of tertiary and quaternary amine local anesthetics in their ability to depress membrane ionic conductances.J. Neurobiol. 3:267PubMedGoogle Scholar
  20. 20.
    Ohnishi, S., Ito, T. 1974. Calcium-induced phase separations in phosphatidylserine-phosphatidylcholine membranes.Biochemistry 13:881Google Scholar
  21. 21.
    Papahadjopoulos, D. 1970. Phospholipid model membranes. III. Antagonistic effects of Ca++ and local anesthetics on the permeability of phosphatidylserine vesicles.Biochim. Biophys. Acta 211:467PubMedGoogle Scholar
  22. 22.
    Seeman, P. 1966. Erythrocyte membrane stabilization by local anesthetics and tranquilizers.Biochem. Pharmacol. 15:1753CrossRefGoogle Scholar
  23. 23.
    Seeman, P., Kwant, W.O., Goldberg, M., Chau-Wong, M. 1971. The effect of ethanol and chlorpromazine on the membrane permeability to Na++.Biochim. Biophys. Acta 241:349PubMedGoogle Scholar
  24. 24.
    Seeman, P., Kwant, W.O., Sauks, T., Argent, W. 1969. Membrane expansions of intact erythrocytes by anesthetics.Biochim. Biophys. Acta 183:490PubMedGoogle Scholar
  25. 25.
    Shanes, A.M., Freygang, W.H., Grundfest, H., Amatniek, E. 1959. Anesthetic and calcium action in the voltage clamped squid giant axon.J. Gen. Physiol. 42:793PubMedGoogle Scholar
  26. 26.
    Skou, J.C. 1961. The effect of drugs on cell membranes with special reference to local anesthetics.J. Pharm. Pharmacol. 13:204Google Scholar

Copyright information

© Springer-Verlag New York Inc 1975

Authors and Affiliations

  • R. B. Gunn
    • 1
  • J. A. CooperJr.
    • 1
  1. 1.Department of Physiology and PharmacologyDuke University Medical CenterDurham

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