Skip to main content
PMC home page
Biophysical Journal logoLink to Biophysical Journal
. 1982 Mar;37(3):625–631.

The kinetics of local anesthetic blockade of end-plate channels.

R L Ruff
PMCID: PMC1328847  PMID: 6978739

Abstract

The effect of the local anesthetic QX222 on the kinetics of miniature end-plate currents (MEPC)and acetylcholine-induced end-plate current fluctuations was studied in voltage-clamped frog cutaneous pectoris neuromuscular junctions. The rate constants for a kinetic scheme of local anesthetic blockage of end-plate channels were calculated from the MEPC decay parameters. At 18 degrees C the blocking rate constant was 1.1 +/- 0.3 x 10(7) exp (-0.009 +/- 0.003 x V)s -1M-1, and the unblocking rate constant was 5.7 +/- 0.6 exp (0.011 +/- 0.002 x V)s -1. The dissociation constant was close to 10 microM at -80 mV. End-plate fluctuations indicated that the local anesthetic QX222 lowered the effective single-channel conductance, suggesting a finite blocked state conductance that was calculated to be 1.6 pS. The apparent differences between QX222 interaction with end-plate and extrajunctional channels are discussed.

Full text

PDF
625

Selected References

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

  1. Adams D. J., Dwyer T. M., Hille B. The permeability of endplate channels to monovalent and divalent metal cations. J Gen Physiol. 1980 May;75(5):493–510. doi: 10.1085/jgp.75.5.493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Adams P. R., Feltz A. End-plate channel opening and the kinetics of quinacrine (mepacrine) block. J Physiol. 1980 Sep;306:283–306. doi: 10.1113/jphysiol.1980.sp013397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Adams P. R., Feltz A. Quinacrine (mepacrine) action at frog end-plate. J Physiol. 1980 Sep;306:261–281. doi: 10.1113/jphysiol.1980.sp013396. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. 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]
  7. 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]
  8. 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]
  9. Beam K. G. A voltage-clamp study of the effect of two lidocaine derivatives on the time course of end-plate currents. J Physiol. 1976 Jun;258(2):279–300. doi: 10.1113/jphysiol.1976.sp011420. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Deguchi T., Narahashi T. Effects of procaine on ionic conductances of end-plate membranes. J Pharmacol Exp Ther. 1971 Feb;176(2):423–433. [PubMed] [Google Scholar]
  12. 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]
  13. Dwyer T. M., Adams D. J., Hille B. The permeability of the endplate channel to organic cations in frog muscle. J Gen Physiol. 1980 May;75(5):469–492. doi: 10.1085/jgp.75.5.469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gage P. W., Armstrong C. M. Miniature end-plate currents in voltage-clamped muscle fibre. Nature. 1968 Apr 27;218(5139):363–365. doi: 10.1038/218363b0. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Gage P. W., McBurney R. N. Miniature end-plate currents and potentials generated by quanta of acetylcholine in glycerol-treated toad sartorius fibres. J Physiol. 1972 Oct;226(1):79–94. doi: 10.1113/jphysiol.1972.sp009974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. Kordas M. An attempt at an analysis of the factors determining the time course of the end-plate current. I. The effects of prostigmine and of the ratio of Mg 2+ to Ca 2+ . J Physiol. 1972 Jul;224(2):317–332. doi: 10.1113/jphysiol.1972.sp009897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kordas M. An attempt at an analysis of the factors determining the time course of the end-plate current. II. Temperature. J Physiol. 1972 Jul;224(2):333–348. doi: 10.1113/jphysiol.1972.sp009898. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kordas M. The effect of procaine on neuromuscular transmission. J Physiol. 1970 Aug;209(3):689–699. doi: 10.1113/jphysiol.1970.sp009186. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lewis C. A. Ion-concentration dependence of the reversal potential and the single channel conductance of ion channels at the frog neuromuscular junction. J Physiol. 1979 Jan;286:417–445. doi: 10.1113/jphysiol.1979.sp012629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. 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]
  25. Magleby K. L., Stevens C. F. The effect of voltage on the time course of end-plate currents. J Physiol. 1972 May;223(1):151–171. doi: 10.1113/jphysiol.1972.sp009839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Magleby K. L., Terrar D. A. Factors affecting the time course of decay of end-plate currents: a possible cooperative action of acetylcholine on receptors at the frog neuromuscular junction. J Physiol. 1975 Jan;244(2):467–495. doi: 10.1113/jphysiol.1975.sp010808. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Marty A. Noise and relaxation studies of acetylcholine induced currents in the presence of procaine. J Physiol. 1978 May;278:237–250. doi: 10.1113/jphysiol.1978.sp012301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. 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]
  29. 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]
  30. 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]
  31. 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]
  32. Ruff R. L. Local anesthetic alteration of miniature endplate currents and endplate current fluctuations. Biophys J. 1976 May;16(5):433–439. doi: 10.1016/S0006-3495(76)85699-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. 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]
  34. 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]
  35. 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 Biophysical Journal are provided here courtesy of The Biophysical Society

RESOURCES