The Journal of Membrane Biology

, Volume 76, Issue 2, pp 123–128 | Cite as

Monoclonal antibodies modify acetylcholine-induced ionic channel properties in cultured chick myoballs

  • Gabriella Goldberg
  • Daria Mochly-Rosen
  • Sara Fuchs
  • Yoram Lass
Articles

Summary

Monoclonal antibodies directed against the cholinergic binding site of the acetylcholine receptor were found to alter the ion channel properties in cultured chick “myoballs.” Time and dose dependent reduction in acetylcholine sensitivity was observed. Noise analysis experiments indicated a decrease in the mean single channel conductance and an increase in the mean single channel open time.

Key Words

acetylcholine receptor monoclonal antibody ionic channel ACh noise 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Aharonov, A., Tarrab-Hazdai, R., Silman, I., Fuchs, S. 1977. Immunochemical studies on acetylcholine receptor fromTorpedo californica.Immunochemistry 14:129–137PubMedGoogle Scholar
  2. Alema, S., Cull-Candy, S.G., Miledi, R., Trautmann, A. 1981. Properties of end-plate channels in rats immunized against acetylcholine receptors.J. Physiol (London) 311:251–266Google Scholar
  3. Anderson, C.R., Stevens, C.F. 1973. Voltage clamp analysis of acetylcholine produced end-plate current fluctuations at frog neuromuscular function.J. Physiol. (London) 235:665–691Google Scholar
  4. Bevan, S., Kullberg, R.W., Rice, J. 1978. Acetylcholine-induced conductance fluctuations in cultured human myotubes.Nature (London) 273:469–471Google Scholar
  5. Cull-Candy, S.G., Miledi, R., Trautmann, A. 1978. Acetylcholine-induced channels and transmitter release at human endplates.Nature (London) 271:74–75Google Scholar
  6. Cull-Candy, S.G., Miledi, R., Trautmann, A. 1979. End-plate currents and acetylcholine noise at normal and myasthenic human end-plates.J. Physiol (London) 287:247–265Google Scholar
  7. Cull-Candy, S.G., Miledi, R., Uchitel, O.D. 1980. Diffusion of acetylcholine in the synaptic cleft of normal and myasthenia gravis human endplates.Nature (London) 286:500–502Google Scholar
  8. Delegeane, A.M., McNamee, M.G. 1980. Independent activation of the acetylcholine receptor fromTorpedo californica at two sites.Biochemistry 19:890–896PubMedGoogle Scholar
  9. Dionne, V.E., Steinbach, J.H., Stevens, C.F. 1978. An analysis of the dose-response relationship at voltage-clamped frog neuromuscular junctions.J. Physiol (London) 281:421–444Google Scholar
  10. Drachman, D.B. 1978. Myasthenia gravis.New Engl. J. Med. 298:136–142PubMedGoogle Scholar
  11. Elmqvist, D., Hoffmann, W.W., Kugelberg, J., Quastel, D.M.J. 1964. An electrophysiological investigation of neuromuscular transmission in myasthenia gravis.J. Physiol. (London) 174:417–434Google Scholar
  12. Fambrough, D.M., Drachman, D.B., Satyamurti, S. 1973. Neuromuscular junction in myasthenia gravis: Decreased acetylcholine receptors.Science 182:293–295PubMedGoogle Scholar
  13. Fischbach, G.D., Lass, Y. 1978a. Acetylcholine noise in cultured chick myoballs: A voltage clamp analysis.J. Physiol (London) 280:515–526Google Scholar
  14. Fischbach, G.D., Lass, Y. 1978b. A transition temperature for acetylcholine channel conductance in chick myoballs.J. Physiol. (London) 280:527–536Google Scholar
  15. Fuchs, S. 1979. Immunology of the nicotinic acetylcholine receptor.Curr. Top. Microbiol. Immunol. 85:1–29PubMedGoogle Scholar
  16. Goldberg, G., Mochly-Rosen, D., Fuchs, S., Lass, Y. 1981. Blocking of acetylcholine induced channel by a monoclonal antibody against the binding site in cultured chick myoballs.Neurosci. Abstr. 7:702Google Scholar
  17. Green, D.P.L., Miledi, R., Perez de la Mora, M., Vincent, A. 1975. Acetylcholine receptors.Trans. R. Soc. London B 270:551–559Google Scholar
  18. Hamill, O.P., Sakmann, B. 1981. Multiple conductance states of single acetylcholine receptor channel in embryonic muscle cells.Nature (London) 294:462–464Google Scholar
  19. Heinemann, S., Bevam, S., Kullberg, R., Lindstrom, J., Rice, J. 1977. Modulation of acetylcholine receptor by antibody against the receptor.Proc. Natl. Acad. Sci. USA 74:3090–3094PubMedGoogle Scholar
  20. Hohlfeld, R., Sterz, R., Kalies, I., Peper, K., Weklile, H. 1981. Neuromuscular transmission in experimental autoimmune myasthenia gravis.Pfluegers Arch. 390:156–160Google Scholar
  21. Ito, Y., Miledi, R., Vincent, A., Newson-Davis, J. 1978. Acetylcholine receptors and end-plate electrophysiology in myasthenia gravis.Brain 101:345–368PubMedGoogle Scholar
  22. Katz, B., Miledi, R. 1972. The statistical nature of the acetylcholine potential and its molecular components.J. Physiol. (London) 224:665–700Google Scholar
  23. Katz, B., Miledi, R. 1973. The effect of α-bungarotoxin on acetylcholine receptors.Br. J. Pharmacol. 49:138–139PubMedGoogle Scholar
  24. Katz, B., Miledi, R. 1978. A re-examination of curare action at the motor end-plate.Proc. R. Soc. London B 203:119–133Google Scholar
  25. Köhler, G., Milstein, C. 1975. Continuous cultures of fused cells secreting antibody of predefined specificity.Nature (London) 256:495–497Google Scholar
  26. Lass, Y., Fischbach, G.D. 1976. A discontinuous relation between the acetylcholine activated channel conductance and temperature.Nature (London) 263:150–151Google Scholar
  27. Lennon, V.A., Lambert, E.H. 1980. Myasthenia gravis induced by monoclonal antibodies to acetylcholine receptors.Nature (London) 285:238–240Google Scholar
  28. Mochly-Rosen, D., Bartfeld, D., Eshhar, Z., Tarrab-Hazdai, R., Fuchs, S. 1980. Monoclonal antiacetylcholine receptor antibodies directed against the cholinergic binding site.Isr. J. Med. Sci. 16:806Google Scholar
  29. Mochly-Rosen, D., Fuchs, S. 1981. Monoclonal anti-acetylcholine-receptor antibodies directed aginst the cholinergic binding site.Biochemistry 20:5920–5924PubMedGoogle Scholar
  30. Mochly-Rosen, D., Fuchs, S., Eshhar, Z. 1979. Monoclonal antibodies against determinants of acetylcholine receptor.FEBS Lett. 106:389–392PubMedGoogle Scholar
  31. Pennefather, P., Quastel, M.J. 1980. The effects of myasthenia IgG on miniature end-plate currents in mouse diaphragm.Life Sci. 27:2047–2054PubMedGoogle Scholar
  32. Sheridan, R.E., Lester, H.A. 1977. Rates and equilibria at the acetylcholine receptor ofElectrophorus electroplaques: A study of neurally evoked post-synaptic currents and voltage jump relaxations.J. Gen. Physiol. 70:187–219PubMedGoogle Scholar
  33. Sheridan, R.E., Lester, H.A. 1982. Functional stoichiometry at nicotinic receptor. The photon cross section for phase 1 corresponds to two bio-Q molecules per channel.J. Gen. Physiol. 80:499–515PubMedGoogle Scholar
  34. Souroujon, M.C., Mochly-Rosen, D., Gordon, A.S., Fuchs, S. 1983. Interaction of monoclonal antibodies toTorpedo acetylcholine receptor with the receptor of skeletal muscle.Nerve Muscle (in press) Google Scholar
  35. Steinbach, J.H. 1980. Activation of nicotinic acetylcholine receptors.In: The Cell Surface and Neuronal Function. C.W. Cotman, G. Poste, and G.L. Nicolson, editors. pp. 119–156. Elsevier North-Holland, AmsterdamGoogle Scholar
  36. Trautmann, A., Feltz, A. 1980. Open time of channels activated by binding of two distinct agonists.Nature (London) 286:291–293Google Scholar
  37. Vincent, A. 1980. Immunology of acetylcholine receptors in relation to myasthenia gravis.Physiol. Rev. 60:756–824PubMedGoogle Scholar
  38. Zingsheim, H.P., Barrantes, F.J., Frank, J., Hanicke, W., Neugebauer, D.C. 1982. Direct structural localization of two toxin-recognition sites on an ACh receptor protein.Nature (London) 299:81–84Google Scholar

Copyright information

© Springer-Verlag 1983

Authors and Affiliations

  • Gabriella Goldberg
    • 1
  • Daria Mochly-Rosen
    • 2
  • Sara Fuchs
    • 2
  • Yoram Lass
    • 1
  1. 1.Department of Physiology & Pharmacology, Sackler School of MedicineTel-Aviv UniversityRamat-AvivIsrael
  2. 2.Department of Chemical ImmunologyThe Weizmann Institute of ScienceRehovotIsrael

Personalised recommendations