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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1984 Jun;81(12):3901–3904. doi: 10.1073/pnas.81.12.3901

Spontaneous openings of the acetylcholine receptor channel.

M B Jackson
PMCID: PMC345330  PMID: 6328531

Abstract

Patch clamp recordings from embryonic mouse muscle cells in culture revealed spontaneous openings of the acetylcholine receptor channel in the absence of exogenously applied cholinergic agent. The conductance of the spontaneous channel currents was, within experimental error, identical with the conductance of suberyldicholine-activated channel currents. The comparison of channel conductance was made with sodium and with cesium, each at two concentrations, with the same result. Treatment of the cells with alpha-bungarotoxin blocked the spontaneous channel currents. To determine whether the spontaneous openings were caused by an endogenous agent with cholinergic activity a reactive disulfide bond near the receptor binding site was reduced with dithiothreitol and alkylated with N-ethylmaleimide. This chemical modification reduced the effectiveness with which suberyldicholine and curare activated channel currents but did not reduce the frequency of spontaneous openings. These experiments indicate that the acetylcholine receptor briefly and infrequently fluctuates into an active state in the absence of agonist. Agonist activation of the receptor presumably accelerates this spontaneously occurring process.

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Selected References

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

  1. Ben-Haim D., Landau E. M., Silman I. The role of a reactive disulphide bond in the function of the acetylcholine receptor at the frog neuromuscular junction. J Physiol. 1973 Oct;234(2):305–325. doi: 10.1113/jphysiol.1973.sp010347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bregestovski P. D., Miledi R., Parker I. Calcium conductance of acetylcholine-induced endplate channels. Nature. 1979 Jun 14;279(5714):638–639. doi: 10.1038/279638a0. [DOI] [PubMed] [Google Scholar]
  3. Christian C. N., Daniels M. P., Sugiyama H., Vogel Z., Jacques L., Nelson P. G. A factor from neurons increases the number of acetylcholine receptor aggregates on cultured muscle cells. Proc Natl Acad Sci U S A. 1978 Aug;75(8):4011–4015. doi: 10.1073/pnas.75.8.4011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Colquhoun D., Neher E., Reuter H., Stevens C. F. Inward current channels activated by intracellular Ca in cultured cardiac cells. Nature. 1981 Dec 24;294(5843):752–754. doi: 10.1038/294752a0. [DOI] [PubMed] [Google Scholar]
  5. Colquhoun D., Range H. P. Effects of inhibitors of the binding of iodinated alpha-bungarotoxin to acetylcholine receptors in rat muscle. Mol Pharmacol. 1976 Jul;12(4):519–535. [PubMed] [Google Scholar]
  6. DEL CASTILLO J., KATZ B. A comparison of acetylcholine and stable depolarizing agents. Proc R Soc Lond B Biol Sci. 1957 May 7;146(924):362–368. doi: 10.1098/rspb.1957.0017. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Fambrough D. M. Control of acetylcholine receptors in skeletal muscle. Physiol Rev. 1979 Jan;59(1):165–227. doi: 10.1152/physrev.1979.59.1.165. [DOI] [PubMed] [Google Scholar]
  9. Hamill O. P., Marty A., Neher E., Sakmann B., Sigworth F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. doi: 10.1007/BF00656997. [DOI] [PubMed] [Google Scholar]
  10. Hamill O. P., Sakmann B. Multiple conductance states of single acetylcholine receptor channels in embryonic muscle cells. Nature. 1981 Dec 3;294(5840):462–464. doi: 10.1038/294462a0. [DOI] [PubMed] [Google Scholar]
  11. Jackson M. B., Lecar H., Askanas V., Engel W. K. Single cholinergic receptor channel currents in cultured human muscle. J Neurosci. 1982 Oct;2(10):1465–1473. doi: 10.1523/JNEUROSCI.02-10-01465.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Karlin A., Winnik M. Reduction and specific alkylation of the receptor for acetylcholine. Proc Natl Acad Sci U S A. 1968 Jun;60(2):668–674. doi: 10.1073/pnas.60.2.668. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Katz B., Miledi R. Transmitter leakage from motor nerve endings. Proc R Soc Lond B Biol Sci. 1977 Feb 11;196(1122):59–72. doi: 10.1098/rspb.1977.0029. [DOI] [PubMed] [Google Scholar]
  15. Kistler J., Stroud R. M., Klymkowsky M. W., Lalancette R. A., Fairclough R. H. Structure and function of an acetylcholine receptor. Biophys J. 1982 Jan;37(1):371–383. doi: 10.1016/S0006-3495(82)84685-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. MONOD J., WYMAN J., CHANGEUX J. P. ON THE NATURE OF ALLOSTERIC TRANSITIONS: A PLAUSIBLE MODEL. J Mol Biol. 1965 May;12:88–118. doi: 10.1016/s0022-2836(65)80285-6. [DOI] [PubMed] [Google Scholar]
  17. Neher E., Sakmann B. Single-channel currents recorded from membrane of denervated frog muscle fibres. Nature. 1976 Apr 29;260(5554):799–802. doi: 10.1038/260799a0. [DOI] [PubMed] [Google Scholar]
  18. Neubig R. R., Boyd N. D., Cohen J. B. Conformations of Torpedo acetylcholine receptor associated with ion transport and desensitization. Biochemistry. 1982 Jul 6;21(14):3460–3467. doi: 10.1021/bi00257a032. [DOI] [PubMed] [Google Scholar]
  19. Sakmann B., Noma A., Trautwein W. Acetylcholine activation of single muscarinic K+ channels in isolated pacemaker cells of the mammalian heart. Nature. 1983 May 19;303(5914):250–253. doi: 10.1038/303250a0. [DOI] [PubMed] [Google Scholar]
  20. Shainberg A., Cohen S. A., Nelson P. G. Induction of acetylcholine receptors in muscle cultures. Pflugers Arch. 1976 Feb 24;361(3):255–261. doi: 10.1007/BF00587290. [DOI] [PubMed] [Google Scholar]
  21. Silman I., Karlin A. Acetylcholine receptor: covalent attachment of depolarizing groups at the active site. Science. 1969 Jun 20;164(3886):1420–1421. doi: 10.1126/science.164.3886.1420. [DOI] [PubMed] [Google Scholar]
  22. TAKEUCHI N. Effects of calcium on the conductance change of the end-plate membrane during the action of transmitter. J Physiol. 1963 Jun;167:141–155. doi: 10.1113/jphysiol.1963.sp007137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Trautmann A. Curare can open and block ionic channels associated with cholinergic receptors. Nature. 1982 Jul 15;298(5871):272–275. doi: 10.1038/298272a0. [DOI] [PubMed] [Google Scholar]
  24. Yellen G. Single Ca2+-activated nonselective cation channels in neuroblastoma. Nature. 1982 Mar 25;296(5855):357–359. doi: 10.1038/296357a0. [DOI] [PubMed] [Google Scholar]

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