Skip to main content
SpringerLink
Log in

A theoretical experimental method to determine the locus of desensitization

  • Published:
Bulletin of Mathematical Biology Aims and scope Submit manuscript

Abstract

Consider a ligand-gated channel with n agonist binding sites which can undergo desensitization. We present a theoretical experimental procedure for pinpointing the principal receptor state from which there is a transition to the desensitized state. The method is based on the observation that the dependence of the slope of the time constant of desensitization vs agonist concentration, at low concentrations, represents the state from which desensitization occurs. In those receptors where desensitization occurs from the open state (or the one immediately preceding it), the method also enables us to determine the number of binding sites.

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

  • Adams, P. R. (1987). The Vertebrate Neuromuscular Junction, M. M. Salpeter (Ed.), New York: Alan R. Liss Inc., pp. 317–359.

    Google Scholar 

  • Anwyl, R. and T. Narahashi (1980). Desensitization of the acetylcholine receptor of denervated rat soleus muscle and the effect of calcium. Br. J. Pharmacol. 69, 91–98.

    Google Scholar 

  • Ball, F. G., R. McGee and M. S. P. Sansom (1989). Post-perturbation kinetics of single ion channels. Proc. R. Soc. Ser. B 236, 29–52.

    Google Scholar 

  • Boyd, D. B. (1987). Two distinct phases of desensitization of acetylcholine receptor of clonal rat PC12 cells. J. Physiol. 389, 45–67.

    Google Scholar 

  • Boyd, N. D. and J. B. Cohen (1980). Kinetics of binding of 3H acetylcholine and 3H carbamoylcholine to Torpedo postsynaptic membranes: slow conformational transitions of the cholinergic receptor. Biochem. 19, 5344–5353.

    Article  Google Scholar 

  • Buchman, E. and H. Parnas (1992). Sequential approach to describe the time course of synaptic channel opening under constant transmitter concentration. J. Theor. Biol. 158, 517–534.

    Google Scholar 

  • Buchman, E. and H. Parnas (1994). Sequential approach to describe channel opening and desensitization. J. Theor. Biol. 167, 381–395.

    Article  Google Scholar 

  • Cachelin, A. B. and D. Colquhoun (1989). Desensitization of the acetylcholine receptor of frog end-plates measured in a vaseline-gap voltage clamp. J. Physiol. (Lond.) 415, 159–188.

    Google Scholar 

  • Changeux, J. P., A. Devillers-Thiery and P. Chemouilli (1984). Acetylcholine receptor: an allosteric protein. Science 225, 1335–1345.

    Google Scholar 

  • Changeux, J. P., M. Kasai and C. Y. Lee (1970). Use of a snake venom toxin to characterize the cholinergic receptor protein. Proc. Natl. Acad. Sci. USA 67, 1241.

    Article  Google Scholar 

  • Chesnut, T. J. (1983). Two-component desensitization at the neuromuscular junction of the frog. J. Physiol. (Lond.) 336, 229–241.

    Google Scholar 

  • Clark, R. B. and P. R. Adams (1981). Rapid flow measurements of desensitization at frog end-plates. Biophys. J. 33, 16a.

    Google Scholar 

  • Colquhoun, D. and D. C. Ogden (1988). Activation of ion channels in the frog end-plate by high concentrations of acetylcholine. J. Physiol. (Lond.) 395, 131–159.

    Google Scholar 

  • Colquhoun, D. and B. Sakmann (1985). Fast events in single-channel currents activated by acetylcholine and its analogue at the frog muscle end-plate. J. Physiol. (Lond.) 369, 501–557.

    Google Scholar 

  • Connor, E. A., J. F. Fiekers, D. S. Neel, R. L. Parsons and R. M. Schnitzler (1984). Comparison of cholinergic activation and desensitization at snake twitch and slow muscle end-plates. J. Physiol. 351, 657–674.

    Google Scholar 

  • Dilger, J. P. and R. S. Brett (1990). Direct measurement of the concentration-and time-dependent open probability of the nicotinic acetylcholine receptor channel. Biophys. J. 57, 723–731.

    Google Scholar 

  • Dreyer, F., K. Peper and R. Sterz (1978). Determination of dose-response curves by quantitative iontophoresis at the frog neuromuscular junction. J. Physiol. (Lond.) 281, 395–419.

    Google Scholar 

  • Dudel, J., Ch. Franke and W. Luboldt (1993). Reaction scheme for the glutamate-ergic, quisqualate type, completely desensitizing channels on crayfish muscle. Neurosci. Lett. 158, 177–180.

    Article  Google Scholar 

  • Feltz, A. and A. Trautmann (1982). Desensitization at the frog neuromuscular junction: a biphasic process. J. Physiol. (Lond.) 322, 257–272.

    Google Scholar 

  • Fiekers, J. F., P. M. Spannbauer, B. Scubon-Mulieri and R. L. Parsons (1980). Voltage dependence of desensitization. Influence of calcium and activation kinetics. J. Gen. Physiol. 75, 511–529.

    Article  Google Scholar 

  • Franke, Ch., H. Hatt, H. Parnas and J. Dudel (1991). Kinetic constants of the Ach-receptor reaction deduced from the rise in open probability after steps in Ach concentration. Biophys. J. 60, 1008–1016.

    Google Scholar 

  • Franke, Ch., H. Parnas, G. Hovav and J. Dudel (1993). A molecular scheme for the reaction between acetylcholine and nicotinic channels. Biophys. J. 64, 339–356.

    Google Scholar 

  • Heckmann, M. and J. Dudel (1997). Desensitization and resensitization kinetics of glutamate receptor channels from Drosophila Larval muscle. Biophys. J. 72, 2160–2169.

    Google Scholar 

  • Heidmann, T., J. Bernhardt, E. Neumann and J. P. Changeux (1983). Rapid kinetics of agonist binding and permeability response analysed in parallel on acetylcholine receptor rich membranes from Torpedo marmorata. Biochem. 22, 5452–5459.

    Article  Google Scholar 

  • Jackson, M. B. (1989). Perfection of a synaptic receptor: kinetics and energetics of the acetylcholine receptor. Proc. Natl. Acad. Sci. U.S.A. 86, 2199–2203.

    Article  Google Scholar 

  • Katz, B. and S. Thesleff (1957). A study of the ‘desensitization’ produced by acetylcholine at the motor end-plate. J. Physiol. (Lond.) 138, 63–80.

    Google Scholar 

  • Land, B. R., W. V. Harris, E. E. Salpeter and M. M. Salpeter (1984). Diffusion and binding constants for acetylcholine derived from the falling phase of miniature end-plate currents. Proc. Natl. Acad. Sci. U.S.A. 81, 1594–1598.

    Article  Google Scholar 

  • Magazanik, L. G. and F. Vyskocil (1970). Dependence of acetylcholine desensitization on the membrane potential of frog muscle fiber and on the ionic changes in the medium. J. Physiol. (Lond.) 210, 507–518.

    Google Scholar 

  • Magleby, K. L. and B. S. Pallotta (1981). A study of desensitization of acetylcholine receptors using nerve-released transmitter in the frog. J. Physiol. (Lond.) 316, 225–250.

    Google Scholar 

  • Manthey, A. A. (1966). The effect of calcium on desensitization of membrane receptors at the neuromuscular junction. J. Gen. Physiol. 49, 963–976.

    Article  Google Scholar 

  • Manthey, A. A. (1970). Further studies on the effect of calcium on the time course of action of carbamoylcholine at the neuromuscular junction. J. Gen. Physiol. 56, 407–419.

    Article  Google Scholar 

  • Miledi, R. (1980). Intracellular calcium and desensitization of acetylcholine receptors. Proc. R. Soc. Ser. B 209, 447–452.

    Google Scholar 

  • Naranjo, D. and P. Brehm (1993). Modal shifts in acetylcholine receptor channel gating confer subunit-dependent desensitization. Science 260, 1811–1814.

    Google Scholar 

  • Neubig, R. R. and J. B. Cohen (1979). Equilibrium binding of 3H-tubocurarine and 3H-acetylcholine by Torpedo postsynaptic membranes: stoichometry and ligand interactions. Biochem. 18, 5464–5475.

    Article  Google Scholar 

  • Pallotta, B. S. and G. D. Webb (1980). The effects of external Ca2+ and Mg2+ on the voltage sensitivity of desensitization in Electrophoras electroplaques. J. Gen. Physiol. 75, 693–708.

    Article  Google Scholar 

  • Parnas, H., M. Flashner and M. E. Spira (1989). Sequential model to describe the nicotinic synaptic current. Biophys. J. 55, 875–884.

    Article  Google Scholar 

  • Pennefather, P. and D. M. J. Quastel (1982). Fast desensitization of the nicotinic receptor at the mouse neuromuscular junction. Br. J. Pharmacol. 77, 395–404.

    Google Scholar 

  • Scubon-Mulieri, B. and R. L. Parsons (1978). Desensitization onset and recovery at the potassium-depolarized frog neuromuscular junction are voltage sensitive. J. Gen. Physiol. 71, 285–299.

    Article  Google Scholar 

  • Sine, S. M. and P. Taylor (1979). Functional consequences of agonist-mediated state transitions in the cholinergic receptor. Studies on cultured muscle cells. J. Biol. Chem. 254, 3315–3325.

    Google Scholar 

  • Slater, N. T., A. F. Hall and D. O. Carpenter (1984). Kinetic properties of cholinergic desensitization in Aplysia neurons. Proc. R. Soc. Ser. B 223, 63–78.

    Article  Google Scholar 

  • Tour, O., H. Parnas and I. Parnas (1995). The double ticker: an improved fast drug-application system reveals desensitization of the glutamate channel from a closed state. Eur. J. Neurosci. 7, 2093–2100.

    Article  Google Scholar 

  • Trautmann, A. (1983). A comparative study of the activation of the cholinergic receptor by various agonists. Proc. R. Soc. Lond. Ser. B Biol. Sci. 218, 241–251.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurobiology and Otto Loewi Minerva Center for Cellular and Molecular Neurobiology, The Hebrew University of Jerusalem, Jerusalem, 91904, Israel

    E. Buchman & H. Parnas

Authors
  1. E. Buchman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. Parnas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to H. Parnas.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Buchman, E., Parnas, H. A theoretical experimental method to determine the locus of desensitization. Bull. Math. Biol. 61, 963–986 (1999). https://doi.org/10.1006/bulm.1999.0121

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1006/bulm.1999.0121

Keywords

Search

Navigation