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. 1978 Apr;277:153–176. doi: 10.1113/jphysiol.1978.sp012267

Local anaesthetics transiently block currents through single acetylcholine-receptor channels.

E Neher, J H Steinbach
PMCID: PMC1282384  PMID: 306437

Abstract

1. Single channel currents through acetylcholine receptor channels (ACh channels) were recorded at chronically denervated frog muscle extrajunctional membranes in the absence and presence of the lidocaine derivatives QX-222 and QX-314. 2. The current wave forms due to the opening and closing of single ACh channels (activated by suberyldicholine) normally are square pulses. These single pulses appear to be chopped into bursts of much shorter pulses, when the drug QX-222 is present in addition to the agonist. 3. The mean duration of the bursts is comparable to or longer than the normal channel open time, and increases with increasing drug concentration. 4. The duration of the short pulses within a burst decreases with increasing drug concentration. 5. It is concluded that drug molecules reversibly block open end-plate channels and that the flickering within a burst represents this fast, repeatedly occurring reaction. 6. The voltage dependence of the reaction rates involved, suggested that the site of the blocking reaction is in the centre of the membrane, probably inside the ionic channel.

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Selected References

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

  1. Adams P. R. Drug blockade of open end-plate channels. J Physiol. 1976 Sep;260(3):531–552. doi: 10.1113/jphysiol.1976.sp011530. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Adams P. R. Voltage jump analysis of procaine action at frog end-plate. J Physiol. 1977 Jun;268(2):291–318. doi: 10.1113/jphysiol.1977.sp011858. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Armstrong C. M. Interaction of tetraethylammonium ion derivatives with the potassium channels of giant axons. J Gen Physiol. 1971 Oct;58(4):413–437. doi: 10.1085/jgp.58.4.413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Armstrong C. M. Time course of TEA(+)-induced anomalous rectification in squid giant axons. J Gen Physiol. 1966 Nov;50(2):491–503. doi: 10.1085/jgp.50.2.491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Beam K. G. A quantitative description of end-plate currents in the presence of two lidocaine derivatives. J Physiol. 1976 Jun;258(2):301–322. doi: 10.1113/jphysiol.1976.sp011421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Betz W., Sakmann B. Effects of proteolytic enzymes on function and structure of frog neuromuscular junctions. J Physiol. 1973 May;230(3):673–688. doi: 10.1113/jphysiol.1973.sp010211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Frazier D. T., Narahashi T., Yamada M. The site of action and active form of local anesthetics. II. Experiments with quaternary compounds. J Pharmacol Exp Ther. 1970 Jan;171(1):45–51. [PubMed] [Google Scholar]
  10. Hille B. Local anesthetics: hydrophilic and hydrophobic pathways for the drug-receptor reaction. J Gen Physiol. 1977 Apr;69(4):497–515. doi: 10.1085/jgp.69.4.497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Katz B., Miledi R. The effect of procaine on the action of acetylcholine at the neuromuscular junction. J Physiol. 1975 Jul;249(2):269–284. doi: 10.1113/jphysiol.1975.sp011015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Katz B., Miledi R. The statistical nature of the acetycholine potential and its molecular components. J Physiol. 1972 Aug;224(3):665–699. doi: 10.1113/jphysiol.1972.sp009918. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Maeno T., Edwards C., Hashimura S. Difference in effects of end-plate potentials between procaine and lidocaine as revealed by voltage-clamp experiments. J Neurophysiol. 1971 Jan;34(1):32–46. doi: 10.1152/jn.1971.34.1.32. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Marty A., Neild T., Ascher P. Voltage sensitivity of acetylcholine currents in Aplysia neurones in the presence of curare. Nature. 1976 Jun 10;261(5560):501–503. doi: 10.1038/261501a0. [DOI] [PubMed] [Google Scholar]
  16. Narahashi T., Frazier D. T. Site of action and active form of procaine in squid giant axons. J Pharmacol Exp Ther. 1975 Sep;194(3):506–513. [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. Ruff R. L. A quantitative analysis of local anaesthetic alteration of miniature end-plate currents and end-plate current fluctuations. J Physiol. 1977 Jan;264(1):89–124. doi: 10.1113/jphysiol.1977.sp011659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Steinbach A. B. A kinetic model for the action of xylocaine on receptors for acetylcholine. J Gen Physiol. 1968 Jul;52(1):162–180. doi: 10.1085/jgp.52.1.162. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Steinbach A. B. Alteration by xylocaine (lidocaine) and its derivatives of the time course of the end plate potential. J Gen Physiol. 1968 Jul;52(1):144–161. doi: 10.1085/jgp.52.1.144. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Stevens C. F. Inferences about membrane properties from electrical noise measurements. Biophys J. 1972 Aug;12(8):1028–1047. doi: 10.1016/S0006-3495(72)86141-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Strichartz G. R. The inhibition of sodium currents in myelinated nerve by quaternary derivatives of lidocaine. J Gen Physiol. 1973 Jul;62(1):37–57. doi: 10.1085/jgp.62.1.37. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Wagner H. H., Ulbricht W. The rates of saxitoxin action and of saxitoxin-tetrodotoxin interaction at the node of Ranvier. Pflugers Arch. 1975 Sep 29;359(4):297–315. doi: 10.1007/BF00581441. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Yeh J. Z., Narahashi T. Kinetic analysis of pancuronium interaction with sodium channels in squid axon membranes. J Gen Physiol. 1977 Mar;69(3):293–323. doi: 10.1085/jgp.69.3.293. [DOI] [PMC free article] [PubMed] [Google Scholar]

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