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The Blockade of Open Channel of Acetylcholine Receptor is Responsible for Selective Blockade of Nicotinic Transmission

  • Vladimir I. Skok

Abstract

Hexamethonium, a selective ganglionic blocker, at its lowest effective concentration exhibits the open-channel blockade of nicotinic acetylcholine (ACh) receptors in sympathetic ganglion neurones, with no signs of their competitive blockade. This is evidenced by the facts that 1) hexamethonium shortens in a voltage-dependent manner the apparent mean channel lifetime estimated from the excitatory postsynaptic current (EPSC) decay and from the ACh noise analysis as well as from the analysis of single channel activity, and 2) the hexamethonium-induced reduction of the ACh current amplitude is enhanced by the preliminary opening of the ACh-gated channels.

The rate constants that characterize binding of hexamethonium, pirilenum and some other selective ganglionic blockers to an open ACh-gated channel correlates with their ganglion-blocking activities, in contrast to what is observed in the effects of competitive ganglionic blockers tubocurarine and trimethaphan. This observation suggests that selective ganglionic blockade produced by some compounds is due to an open-channel blockade while in other cases it is due to a competitive mechanism. The selective blockade of open channel can be observed in different types of synapses. It is suggested that the site in the ACh-gated open channel that binds selective blockers normally binds Ca2+ ions.

Keywords

Open Channel Sympathetic Ganglion Selective Blockade Single Channel Activity Nicotinic AChR 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Adams, P.R., 1976, Drug blockade of open end-plate channels. J. Physiol. 260: 531–552.PubMedGoogle Scholar
  2. Adams, P.R., and Feltz, A. 1980, Quinacrine (mepacrine) action at frog end-plate. J. Physiol. 306: 261–281.PubMedGoogle Scholar
  3. Armstrong, C., 1971, Interaction of tetraethylammonium ion derivatives with the potassium channels of giant axons. J. Gen. Physiol. 58: 413–437.PubMedCrossRefGoogle Scholar
  4. Armstrong, C., and Hille, B., 1972, The inner quaternary ammonium ion receptor in potassium channels of the node of Ranvier. J. Gen. Physiol. 59: 388–400.PubMedCrossRefGoogle Scholar
  5. Ascher, P., Marty, A., and Neild, T.O., 1978a, Life-time and elementary conductance of the channels mediating the excitatory effects of acetylcholine in Aplysia neurones.Google Scholar
  6. Ascher, P., Marty, A., and Neild, T.O., 1978b, The mode of action of antagonists on the excitatory response to acetylcholine in Aplysia neurones. J. Physiol. 278: 207–235.PubMedGoogle Scholar
  7. Ascher, P., Large, W.A., and Rang, H.P., 1979, Studies of the mechanism of action of acetylcholine antagonists on rat parasympathetic ganglion cells. J. Physiol. 295: 139–170.PubMedGoogle Scholar
  8. Banks, B.E.C., Brown, C., Burgess, G.M., Burnstock, G., Claret, M., Cocks, T.M., and Jenkinson, D.H., 1979, Apamine blocks certain neurotransmitter-induced increases in potassium permeability. Nature. 282: 415–417.PubMedCrossRefGoogle Scholar
  9. Barker, J.L., 1975, CNS depressants: effects on post-synaptic pharmacology. Brain Research. 92: 35–55.PubMedCrossRefGoogle Scholar
  10. Barlow, R.B., Zoller, A., 1964, Some effects of long-chain polymethylene bis-onium salts on junctional transmission in the peripheral nervous system. Brit. J. Pharmacol. 23: 131–510.PubMedGoogle Scholar
  11. Blackman, J.C., 1970, Dependence on membrane potential of the blocking action of hexamethonium at a sympathetic ganglionic synapse. Proc. Univ. Otago Med. Sch. 48: 4–5.Google Scholar
  12. Bowman, W.C., and Webb, S.W., 1972, Neuromuscular blocking and ganglion blocking activities of some acetylcholine antagonists in the cat. J. Pharmac. Pharmacol. 24: 762–772.CrossRefGoogle Scholar
  13. Bregestovski, P.D., Miledi, R., and Parker, I., 1979, Calcium conductance of acetylcholine-induced end-plate channels. Nature. 279: 638–639.PubMedCrossRefGoogle Scholar
  14. Chang, H.-W., Neumann, E., 1976, Dynamic properties of isolated acetylcholine receptor and chemical mediators. Kinetic studies by acetylcholine binding. Proc. NatT1. Acad. Sci, USA. 73: 3364–3368.PubMedCrossRefGoogle Scholar
  15. Chemeris, N.K., Kazachenko, V.N., Kislov, A.N., and Kurchikov, A.L., 1982, Inhibition of acetylcholine responses by intracellular calcium in Limnea stagnalis neurones. J. Physiol. 323: 1–19.PubMedGoogle Scholar
  16. Clark, R.B., Donaldson, P.L., Gration, K.A.F., Lambert, J.J., Piek, T., Ramsey, R., Apanjer, W., and Usherwood, P.N.R., 1982, Block of Locust muscle glutamate receptors by δ-philanthotoxin occurs after receptor activations. Brain Research. 24: 105–114.CrossRefGoogle Scholar
  17. Colquhoun, D., 1979, The link between drug binding and response: theories and observations, in: The Receptors. A Comprehensive Treatise. Ed. R.D. O’Brien, vol. 1: 93–141, Plenum Press, New York.Google Scholar
  18. Colquhoun, D., and Ogden, D.C., 1984, Evidence from single-channel recording of channel block by nicotinic agonists at the frog neuromuscular junction. J. Physiol. 353: 90 P.Google Scholar
  19. Colquhoun, D., and Sakmann, B., 1983, Bursts of openings in transmitter- activated ion channels, in: Single-Channel Recording, p. 345–364, Sakmann, B., and Neher, E., ed., Plennum Press, New York.Google Scholar
  20. Colquhoun, D., and Sheridan, R.E., 1982, The effect of tubocurarine competition on the kinetics of agonist action on the nicotinic receptor. Br. J. Pharmacol. 75: 77–86.PubMedGoogle Scholar
  21. Connor, E.A., Neel, D.S., and Parsons, R.L., 1985, Influence of the extracellular ionic environment on ganglionic fast excitatory postsynaptic currents. Brain Research. 339: 227–235.PubMedCrossRefGoogle Scholar
  22. Derkach, V.A., Selyanko, A.A., and Skok, V.I,, 1983, Acetylcholine-induced current fluctuations and fast excitatory post-synaptic currents in rabbit sympathetic neurones. J. Physiol. 336: 511–526.PubMedGoogle Scholar
  23. Derkach, V.A., North, R.A., Selyanko, A.A., and Skok, V.I., 1986, Single channels activated by acetylcholine in rat cervical ganglion. In press.Google Scholar
  24. Dreyer, F., Muller, K.-D., Peper, K., and Sterz, R., 1976, The m1 omohyoideus of the mouse as a convenient mammalian muscle preparation. A study of junctional and extrajunctional acetylcholine receptors by noise analysis and cooperativity. Pflügers Archiv. 367: 115–122.PubMedCrossRefGoogle Scholar
  25. Eldefrawi, M.E., Eldefrawi, A.T., Penfield, L.A., O’Brein, R.D., and Campen, E., 1975, Binding of calcium and zinc to the acetylcholine receptor purified from Torpedo californica. Life Sciences. 16: 925–935.CrossRefGoogle Scholar
  26. Gillo, B., and Lass, Y., 1984, The mechanism of steroid anaesthetic (alphxalone) block of acetylcholine-induced ionic currents. Br. J. Pharmacol. 82: 783–789.PubMedGoogle Scholar
  27. Grob, D., 1967, Neuromuscular blocking drugs, in: Physiological Pharmacology. III/C 389–460, Root, W.S., and Hofman, W.S., ed., Academic Press, New York.Google Scholar
  28. Gurney, A.M., and Rang, H.P., 1984, The channel-blocking action of methonium compounds on rat submandibular ganglion cells. Br. J. Pharmacol. 82: 623–642.PubMedGoogle Scholar
  29. Guyton, A.C., Reeder, R.C., 1950, Quantitative studies on the autonomic actions of curare. J. Pharmacol. Exp. Ther. 98: 188–194.PubMedGoogle Scholar
  30. Hamill, O.P., Marty, A., Neher, E., Sakmann, B, and Sigworth, F. J., 1981, Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflügers Arch., 391: 85–100.PubMedCrossRefGoogle Scholar
  31. Hille, B., Courtney, K., and Dum, R., 1975, Rate and site of action of local anaesthetics in myelinated nerve fibres, in: Molec. mechanisms of Anaesthesia. Progress in Anesthesiology.Google Scholar
  32. Karlin, A., Cox, R., Kaldany, R.-R., Lober, P., and Holtzmanman, E., 1983, The arrangement and functions of the chains of the acetylcholine receptor of Torpedo electric tissue, in: Molecular Neurobiology. Cold Spring Harbor Symposia on Quantitative Biology. 48: 1–8.Google Scholar
  33. Kuba, K., and Takeshita, S., 1983, On the mechanism of calcium action on the acetylcholine receptor-channel complex at the frog end-plate membrane. Jap. J. Physiol. 33: 931–944.CrossRefGoogle Scholar
  34. Kuffler, S.W., and Yoshikami, D., 1975. The number of transmitter molecules in a quantum: an estimate from iontophoretic application of acetylcholine at the neuromuscular synapse. J. Physiol. 251: 465–484.PubMedGoogle Scholar
  35. Lingle, Ch., 1983, Blockade of cholinergic channels by chlorisondamine on a crustacean muscle. J. Physiol. 339: 395–417.PubMedGoogle Scholar
  36. Lingle, Ch., 1983, Different types of blockade of crustacean acetylcholine-induced currents. J. Physiol. 339: 419–437.PubMedGoogle Scholar
  37. Magazanik, L.G., Antonov, S.M., and Gmiro, V.E., 1984. Kinetics and pharmacological blockade of glutamate-activated postsynaptic ion channels. Biol. Membr. 1: 130–140 (in Russ.)Google Scholar
  38. Marchais, D., and Marty, A., 1979, Interaction of permeant ions with channels activated by acetylcholine in Aplysia neurones. J. Physiol. 297: 9–45.PubMedGoogle Scholar
  39. Marty, A., 1980, Action of calcium ions on acetylcholine-sensitive channels in Aplysia neurones. J. Physiol. 76:523–527, Paris.Google Scholar
  40. Mayer, M.L., Westbrook, G.L., and Guthrie, P.B., 1984, Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones. Nature. 309: 261–263.PubMedCrossRefGoogle Scholar
  41. Nowak, L., Bregestowski, P., and Ascher, P., 1984, Magnesium gates glutamate-activated channels in mouse central neurones. Nature. 307: 462–465.PubMedCrossRefGoogle Scholar
  42. Paton, W.D.M., and Zaimis, E.J., 1949, The pharmacological actions of polymathylene bistrimethylammonium salts. Br. J. Pharmacol. 4: 381–400.Google Scholar
  43. Rang, H.P., 1981, The characteristics of synaptic currents and responses to acetylcholine of rat submandibular ganglion cells. J. Physiol. 311: 23–55.PubMedGoogle Scholar
  44. Sakmann, B., Patlak, J., and Neher, E., 1980, Single acetylcholine activated channels show burst-kinetics in presence of desensitizing concentrations of agonist. Nature. 286: 71–73.PubMedCrossRefGoogle Scholar
  45. Selyanko, A.A., Derkach, V.A., and Skok, V.I., 1981, Effects of some ganglion-blocking agents on fast excitatory postsynaptic currents in mammalian sympathetic ganglion neurones. in: Adv. Physiol. Sci. 4:329–342, Physiology of Excitable Membranes (ed. J. Salanki).Google Scholar
  46. Selyanko, A.A., Derkach, V.A., and Skok, V.I., 1982, Vo11age-dependent actions of short-chain polymethylene bis-trimethylammonium compounds on sympathetic ganglion neurone. J. Auton. Nerv. System, 6: 13–21.CrossRefGoogle Scholar
  47. Selyanko, A.A., Kerkach, V.A., and Skok, V.I., 1985, The effect of Ca2+ ions on the channel-blocking action of hexamethonium in sympathetic ganglion. Proceedings of the USSR Academy of Sciences. 284: 225–228, (in Russian).Google Scholar
  48. Sine, S.M., and Steinbach, J.H., 1984, Agonists block currents through acetylcholine receptor channels. Bio. Phys. J., 46: 277–283.Google Scholar
  49. Skok, V.I., 1986, Channel-blocking mechanism ensures specific blockade of synaptic transmission. Neuroscience, 17: 1–9.PubMedCrossRefGoogle Scholar
  50. Skok, V.I., Selyanko, A.A., and Derkach, V.A., 1983, Channe1-blocking activity is a possible mechanism for a selective ganglionic blockade. Pflügers Archiv. 398: 169–171.PubMedCrossRefGoogle Scholar
  51. Skok, V.1., Selyanko, A.A., Derkach, V.A., Gmiro, V.E., and Lukomskaya, N.Ya., 1984, The mechanisms of ganglion-blocking action of bisammonium compounds. Neirophysiology, 16: 46–52.Google Scholar
  52. Slater, N.T., Carpenter, D.O., Haas, H.L., and David, J.A., 1984, Blocking kinetics at excitatory acetylcholine responses on Aplysia neurons. Biophys. J. 45: 24–25.CrossRefGoogle Scholar
  53. Steinbach, A.B., 1968, A kinetic model for the action of xylocaine on receptors for acetylcholine. J. Gen, Physiol. 52: 162–180.CrossRefGoogle Scholar
  54. Strichartz, G., 1973, The inhibition of sodium currents in myelinated nerve by quaternary derivatives of lidocaine. J. Gen. Physiol. 62: 37–54.PubMedCrossRefGoogle Scholar
  55. Vladimirova, I.A., and Shuba, M.F., 1978, Strychnine, hydrastine and apamin effect on synaptic transmission in smooth muscle cells. Neirophysiology, 10: 295–299.Google Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Vladimir I. Skok
    • 1
  1. 1.Department of the Autonomic Nervous System PhysiologyBogomoletz Institute of PhysiologyKiev-24USSR

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