Skip to main content
The Journal of Physiology logoLink to The Journal of Physiology
. 1981 Jan;310:159–190. doi: 10.1113/jphysiol.1981.sp013542

The kinetics of slow muscle acetylcholine-operated channels in the garter snake.

V E Dionne
PMCID: PMC1274733  PMID: 6262503

Abstract

1. Slow muscle synaptic responses were modelled kinetically in an attempt to define the mechanism by which slow fibre acetylcholine-operated channels differ from those in twitch fibres. 2. Three kinetically distinguishable states were necessary. 3. All applicable three-state kinetic schemes were considered in an attempt to identify the simplest description of the data. Experimental tets eliminated several models. Two models were not tested because they contained an excessive number of adjustable parameters. 4. The data were not fitted by kinetic schemes which postulated (i) channels which opened with one as well as two bound agonist molecules, (ii) channels which became blocked after opening, or (iii) separate populations of synaptic and extrasynaptic channels. 5. The three-state kinetic model of del Castillo & Katz (1957) accurately described all the data. This sequential model relates a closed channel state with no agonist bound to its receptors, an intermediate state (also closed) with agonist bound, and an open channel state. It is the same model which has been used to describe synaptic responses in twitch fibres. 6. The variation which allows this model to describe both twitch and slow fibre synaptic responses is the lifetime of the intermediate state. In twitch fibres the intermediate state lifetime is undetectably brief by electrophysiological methods. However, in slow fibres this lifetime appears to be 1-2 msec, varying with voltage. 7. Three of the four transition rates in this three-state kinetic scheme may be estimated by fitting the model to the data. These are the channel opening rate, the channel closing rate and the rate at which closed channels lose their bound agonist molecules. The latter two rates appear to depend exponentially on voltage. The channel opening rate was not detectably voltage-sensitive.

Full text

PDF
166

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adams P. R. Kinetics of agonist conductance changes during hyperolarization at frog endplates. Br J Pharmacol. 1975 Feb;53(2):308–310. doi: 10.1111/j.1476-5381.1975.tb07364.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Adams P. R., Sakmann B. Decamethonium both opens and blocks endplate channels. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2994–2998. doi: 10.1073/pnas.75.6.2994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Adams P. R. Voltage dependence of agonist responses at voltage-clamped frog endplates. Pflugers Arch. 1976 Jan 30;361(2):145–151. doi: 10.1007/BF00583458. [DOI] [PubMed] [Google Scholar]
  4. Anderson C. R., Cull-Candy S. G., Miledi R. Glutamate current noise: post-synaptic channel kinetics investigated under voltage clamp. J Physiol. 1978 Sep;282:219–242. doi: 10.1113/jphysiol.1978.sp012459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Anderson C. R., Stevens C. F. Voltage clamp analysis of acetylcholine produced end-plate current fluctuations at frog neuromuscular junction. J Physiol. 1973 Dec;235(3):655–691. doi: 10.1113/jphysiol.1973.sp010410. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Barker J. L., McBurney R. N. GABA and glycine may share the same conductance channel on cultured mammalian neurones. Nature. 1979 Jan 18;277(5693):234–236. doi: 10.1038/277234a0. [DOI] [PubMed] [Google Scholar]
  7. Colquhoun D., Dionne V. E., Steinbach J. H., Stevens C. F. Conductance of channels opened by acetylcholine-like drugs in muscle end-plate. Nature. 1975 Jan 17;253(5488):204–206. doi: 10.1038/253204a0. [DOI] [PubMed] [Google Scholar]
  8. Colquhoun D., Hawkes A. G. Relaxation and fluctuations of membrane currents that flow through drug-operated channels. Proc R Soc Lond B Biol Sci. 1977 Nov 14;199(1135):231–262. doi: 10.1098/rspb.1977.0137. [DOI] [PubMed] [Google Scholar]
  9. Colquhoun D., Large W. A., Rang H. P. An analysis of the action of a false transmitter at the neuromuscular junction. J Physiol. 1977 Apr;266(2):361–395. doi: 10.1113/jphysiol.1977.sp011772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cull-Candy S. G., Miledi R., Trautmann A. End-plate currents and acetylcholine noise at normal and myasthenic human end-plates. J Physiol. 1979 Feb;287:247–265. doi: 10.1113/jphysiol.1979.sp012657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. DEL CASTILLO J., KATZ B. Interaction at end-plate receptors between different choline derivatives. Proc R Soc Lond B Biol Sci. 1957 May 7;146(924):369–381. doi: 10.1098/rspb.1957.0018. [DOI] [PubMed] [Google Scholar]
  12. Dionne V. E., Parsons R. L. Characteristics of the acetylcholine-operated channel at twitch and slow fibre neuromuscular junctions of the garter snake. J Physiol. 1981 Jan;310:145–158. doi: 10.1113/jphysiol.1981.sp013541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Dionne V. E., Parsons R. L. Synaptic channel gating differences at snake twitch and slow neuromuscular junctions. Nature. 1978 Aug 31;274(5674):902–904. doi: 10.1038/274902a0. [DOI] [PubMed] [Google Scholar]
  14. Dionne V. E., Steinbach J. H., Stevens C. F. An analysis of the dose-response relationship at voltage-clamped frog neuromuscular junctions. J Physiol. 1978 Aug;281:421–444. doi: 10.1113/jphysiol.1978.sp012431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Dionne V. E., Stevens C. F. Voltage dependence of agonist effectiveness at the frog neuromuscular junction: resolution of a paradox. J Physiol. 1975 Oct;251(2):245–270. doi: 10.1113/jphysiol.1975.sp011090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Dudel J. Relaxation after a voltage step of inhibitory synaptic current elicited by nerve stimulation (crayfish neuromuscular junction). Pflugers Arch. 1978 Sep 6;376(2):151–157. doi: 10.1007/BF00581578. [DOI] [PubMed] [Google Scholar]
  17. Gage P. W., Hamill O. P. Lifetime and conductance of acetylcholine-activated channels in normal and denervated toad sartorius muscle. J Physiol. 1980 Jan;298:525–538. doi: 10.1113/jphysiol.1980.sp013099. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gage P. W., McBurney R. N. Effects of membrane potential, temperature and neostigmine on the conductance change caused by a quantum or acetylcholine at the toad neuromuscular junction. J Physiol. 1975 Jan;244(2):385–407. doi: 10.1113/jphysiol.1975.sp010805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Karlin A. On the application of "a plausible model" of allosteric proteins to the receptor for acetylcholine. J Theor Biol. 1967 Aug;16(2):306–320. doi: 10.1016/0022-5193(67)90011-2. [DOI] [PubMed] [Google Scholar]
  20. Katz B., Miledi R. Membrane noise produced by acetylcholine. Nature. 1970 Jun 6;226(5249):962–963. doi: 10.1038/226962a0. [DOI] [PubMed] [Google Scholar]
  21. Kuffler S. W., Yoshikami D. The number of transmitter molecules in a quantum: an estimate from iontophoretic application of acetylcholine at the neuromuscular synapse. J Physiol. 1975 Oct;251(2):465–482. doi: 10.1113/jphysiol.1975.sp011103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Magleby K. L., Stevens C. F. A quantitative description of end-plate currents. J Physiol. 1972 May;223(1):173–197. doi: 10.1113/jphysiol.1972.sp009840. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Matthews-Bellinger J., Salpeter M. M. Distribution of acetylcholine receptors at frog neuromuscular junctions with a discussion of some physiological implications. J Physiol. 1978 Jun;279:197–213. doi: 10.1113/jphysiol.1978.sp012340. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Neher E., Sakmann B. Noise analysis of drug induced voltage clamp currents in denervated frog muscle fibres. J Physiol. 1976 Jul;258(3):705–729. doi: 10.1113/jphysiol.1976.sp011442. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Neher E., Sakmann B. Voltage-dependence of drug-induced conductance in frog neuromuscular junction. Proc Natl Acad Sci U S A. 1975 Jun;72(6):2140–2144. doi: 10.1073/pnas.72.6.2140. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Neher E., Steinbach J. H. Local anaesthetics transiently block currents through single acetylcholine-receptor channels. J Physiol. 1978 Apr;277:153–176. doi: 10.1113/jphysiol.1978.sp012267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Neher E., Stevens C. F. Conductance fluctuations and ionic pores in membranes. Annu Rev Biophys Bioeng. 1977;6:345–381. doi: 10.1146/annurev.bb.06.060177.002021. [DOI] [PubMed] [Google Scholar]
  28. Nelson D. J., Sachs F. Single ionic channels observed in tissue-cultured muscle. Nature. 1979 Dec 20;282(5741):861–863. doi: 10.1038/282861a0. [DOI] [PubMed] [Google Scholar]
  29. Sheridan R. E., Lester H. A. Rates and equilibria at the acetylcholine receptor of Electrophorus electroplaques: a study of neurally evoked postsynaptic currents and of voltage-jump relaxations. J Gen Physiol. 1977 Aug;70(2):187–219. [PMC free article] [PubMed] [Google Scholar]
  30. Thron C. D. On the analysis of pharmacological experiments in terms of an allosteric receptor model. Mol Pharmacol. 1973 Jan;9(1):1–9. [PubMed] [Google Scholar]
  31. Woodhull A. M. Ionic blockage of sodium channels in nerve. J Gen Physiol. 1973 Jun;61(6):687–708. doi: 10.1085/jgp.61.6.687. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES