Skip to main content
SpringerLink
Log in

Ionophore-mediated calcium influx effects on the post-synaptic muscle fibre membrane

  • Letter
  • Published:

From Nature

View current issue Submit your manuscript

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Abstract

THE physiological chemotransmitter acetylcholine and its structural analogues such as carbamylcholine are capable of producing a sustained blockade of neuromuscular transmission when applied to the neuromuscular junction for prolonged periods. This neuromuscular blockade is not due to a depolarisation of the postsynaptic muscle fibre membrane but rather is generally ascribed to the inactivation, or ‘desensitisation’ of cholinergic receptor molecules in the postsynaptic membrane1,2. Various kinetic models involving agonist, and receptor molecules postulated to exist in different conformational states, have been proposed to account for the time course of the desensitisation process2,3. These models do not incorporate the acceleration of desensitisation by calcium ions4,5 and they do not predict correctly the observed effects of certain cholinergic antagonists on desensitisation. Consequently, alternative models for desensitisation have been proposed. In one of them calcium ions accumulate at the interior surface of the post-synaptic membrane and bind to the cholinergic receptors, thereby causing desensitisation by producing or sustaining some inactive receptor conformation6. We tested the model for desensitisation which involves internal calcium binding. This was accomplished by facilitating calcium ion flux across the post-synaptic membrane using the divalent cation ionophore A23187, while simultaneously producing a rapid desensitisation with iontophoretic application of carbamylcholine. Our results provide further evidence that calcium ions are a significant factor in the molecular mechanism of desensitisation.

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. Thesleff, S. Acta physiol. scand. 34, 218–231 (1955).

    Article  CAS  Google Scholar 

  2. Katz, B. & Thesleff, S. J. Physiol., Lond. 138, 63–80 (1957).

    Article  CAS  Google Scholar 

  3. Rang, H. P. & Ritter, J. M. Molec. Pharmac. 6, 357–382 (1970).

    CAS  Google Scholar 

  4. Manthey, A. A. J. gen. Physiol. 49, 963–975 (1966).

    Article  CAS  Google Scholar 

  5. Magazanik, L. G. & Vyskocil, F. J. Physiol., Lond. 210, 507–518 (1970).

    Article  CAS  Google Scholar 

  6. Nastuk, W. L. & Parsons, R. L. J. gen. Physiol. 56, 218–249 (1970).

    Article  CAS  Google Scholar 

  7. Reed, P. W. & Lardy, H. A. in The Role of Membranes in Metabolic Regulation (eds Mehlman, M. A. & Hanson, R. W.) 111–131 (Academic Press, New York, 1972).

    Book  Google Scholar 

  8. McLaughlin, S. & Eisenberg, M. A. Rev. Biophys. Bioengng 4, 335–366 (1975).

    Article  CAS  Google Scholar 

  9. Caswell, A. H. & Pressman, B. C. Biochem. biophys. Res. Commun. 49, 292–298 (1972).

    Article  CAS  Google Scholar 

  10. Scarpa, A., Baldassare, J. & Inesi, G. J. gen. Physiol. 60, 735–749 (1972).

    Article  CAS  Google Scholar 

  11. Hainut, K. & Desmedt, J. E. Nature 252, 407–408 (1974).

    Article  ADS  Google Scholar 

  12. Inoue, F. & Frank, G. B. Br. J. Pharmac. Chemother. 30, 186–193 (1967).

    Article  CAS  Google Scholar 

  13. Okada, K. Jap. J. Physiol. 17, 245–261 (1967).

    Article  CAS  Google Scholar 

  14. Devore, D. I. & Nastuk, W. L. Nature 253, 644–646 (1975).

    Article  ADS  CAS  Google Scholar 

  15. Miledi, R. Proc. R. Soc. B183, 421–425 (1973).

    ADS  CAS  Google Scholar 

  16. Huxley, A. F. J. Physiol., Lond. 243, 1–43 (1974).

    Article  CAS  Google Scholar 

  17. Nastuk, W. L. Fedn Proc. 12, 102 (1953).

    Google Scholar 

  18. Wolfson, C. H. & Nastuk, W. L. Fedn Proc. 34, 404 (1975).

    Google Scholar 

  19. Hartzell, H. C., Kuffler, S. W. & Yoshikami, D. J. Physiol., Lond. 251, 427–463 (1975).

    Article  CAS  Google Scholar 

  20. Wolfson, C. H. thesis, Columbia Univ. (in preparation).

  21. Ebashi, S., Endo, M. & Ohtsuki, I. Q. Rev. Biophys. 2, 351–384 (1969).

    Article  CAS  Google Scholar 

  22. Martinez-Carrion, M. & Raftery, M. A. Biochem. biophys. Res. Commun. 55, 1156–1164 (1973).

    Article  CAS  Google Scholar 

  23. Cohen, J. B., Weber, M. & Changeux, J-P. Molec. Pharmac. 10, 904–932 (1974).

    CAS  Google Scholar 

  24. Chang, H. W. & Neumann, E. Proc. natn. Acad. Sci. U.S.A., 73, 3364–3368. (1976).

    Article  ADS  CAS  Google Scholar 

Download references

Author information

Author notes

  1. DAVID I. DEVORE

    Present address: Department of Chemistry, University of California, Berkeley, California, 94720

Authors and Affiliations

  1. College of Physicians and Surgeons, Columbia University, New York, New York, 10032

    DAVID I. DEVORE & WILLIAM L. NASTUK

Authors
  1. DAVID I. DEVORE
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. WILLIAM L. NASTUK
    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

DEVORE, D., NASTUK, W. Ionophore-mediated calcium influx effects on the post-synaptic muscle fibre membrane. Nature 270, 441–443 (1977). https://doi.org/10.1038/270441a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/270441a0

  • Springer Nature Limited

We’re sorry, something doesn't seem to be working properly.

Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Search

Navigation