Skip to main content
NCBI home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1976 Jun;258(2):301–322. doi: 10.1113/jphysiol.1976.sp011421

A quantitative description of end-plate currents in the presence of two lidocaine derivatives.

K G Beam
PMCID: PMC1308977  PMID: 957158

Abstract

1. Possible ways in which local anaesthetics may act to produce their characteristic alterations of end-plate current (e.p.c.s) are considered. 2. Following Magleby & Stevens (1972b), it is proposed that when acetylcholine (ACh) binds to its end-plate receptor it induces a conformational change which causes an increased ionic permeability and, thus, the measured e.p.c.; the reverse conformational change which returns the permeability to its resting state is postulated to be the rate-limiting event for e.p.c. decay whether or not local anaesthetics are present. Moreover, it is proposed that the ACh receptor had multiple binding sites and the local anaesthetics can bind to one or more of these sites thereby altering the conformational changes induced when ACh binds to remaining sites. 3. Equations based on this proposal are developed and are shown to provide an accurate description of the entire e.p.c. time couse as modified by eith QX-222 or QX-314. 4. Other models are also discussed; models in which local anaesthetic molecules bind only after receptor activation appear to be ruled out.

Full text

PDF
301

Selected References

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

  1. Adams P. R. Proceedings: The mechanism by which amylobarbitone and thiopentone block the end-plate response to nicotinic agonists. J Physiol. 1974 Aug;241(1):41P–42P. [PubMed] [Google Scholar]
  2. 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]
  3. 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]
  4. Brandt K. G., Parks P. C., Czerlinski G. H., Hess G. P. On the elucidation of the pH dependence of the oxidation-reduction potential of cytochrome c at alkaline pH. J Biol Chem. 1966 Sep 25;241(18):4180–4185. [PubMed] [Google Scholar]
  5. Cartaud J., Benedetti E. L., Cohen J. B., Meunier J. C., Changeux J. P. Presence of a lattice structure in membrane fragments rich in nicotinic receptor protein from the electric organ of Torpedo marmorata. FEBS Lett. 1973 Jun 15;33(1):109–113. doi: 10.1016/0014-5793(73)80171-1. [DOI] [PubMed] [Google Scholar]
  6. Changeux J. P., Thiéry J., Tung Y., Kittel C. On the cooperativity of biological membranes. Proc Natl Acad Sci U S A. 1967 Feb;57(2):335–341. doi: 10.1073/pnas.57.2.335. [DOI] [PMC free article] [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. DEL CASTILLO L., KATZ B. A study of curare action with an electrical micromethod. Proc R Soc Lond B Biol Sci. 1957 May 7;146(924):339–356. doi: 10.1098/rspb.1957.0015. [DOI] [PubMed] [Google Scholar]
  9. Dreyer F., Peper K. Density and dose-response curve of acetylcholine receptors in frog neuromuscular junction. Nature. 1975 Feb 20;253(5493):641–643. doi: 10.1038/253641a0. [DOI] [PubMed] [Google Scholar]
  10. Fersht A. R., Requena Y. Equilibrium and rate constants for the interconversion of two conformations of -chymotrypsin. The existence of a catalytically inactive conformation at neutral p H. J Mol Biol. 1971 Sep 14;60(2):279–290. doi: 10.1016/0022-2836(71)90294-4. [DOI] [PubMed] [Google Scholar]
  11. Foidart J. M., Gridelet J. Effects of procaine and d-tubocurarine on the activity of membrane bound acetylcholinesterase. Biochem Pharmacol. 1974 Feb 1;23(3):725–733. doi: 10.1016/0006-2952(74)90637-6. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Gage P. W., McBurney R. N., Schneider G. T. Effects of some aliphatic alcohols on the conductance change caused by a quantum of acetylcholine at the toad end-plate. J Physiol. 1975 Jan;244(2):409–429. doi: 10.1113/jphysiol.1975.sp010806. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hammes G. G. Relaxation spectrometry of biological systems. Adv Protein Chem. 1968;23:1–57. doi: 10.1016/s0065-3233(08)60399-x. [DOI] [PubMed] [Google Scholar]
  15. Jenkinson D. H., Terrar D. A. Influence of chloride ions on changes in membrane potential during prolonged application of carbachol to frog skeletal muscle. Br J Pharmacol. 1973 Feb;47(2):363–376. doi: 10.1111/j.1476-5381.1973.tb08334.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. KATZ B., THESLEFF S. A study of the desensitization produced by acetylcholine at the motor end-plate. J Physiol. 1957 Aug 29;138(1):63–80. doi: 10.1113/jphysiol.1957.sp005838. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Katz B., Miledi R. The characteristics of 'end-plate noise' produced by different depolarizing drugs. J Physiol. 1973 May;230(3):707–717. doi: 10.1113/jphysiol.1973.sp010213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Katz B., Miledi R. The effect of atropine on acetylcholine action at the neuromuscular junction. Proc R Soc Lond B Biol Sci. 1973 Nov 27;184(1075):221–226. doi: 10.1098/rspb.1973.0046. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. 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]
  22. Koshland D. E., Jr A molecular model for the regulatory behavior of enzymes. Harvey Lect. 1971;65:33–57. [PubMed] [Google Scholar]
  23. Kuba K., Albuquerque E. X., Daly J., Barnard E. A. A study of the irreversible cholinesterase inhibitor, diisopropylfluorophosphate, on time course of end-plate currents in frog sartorius muscle. J Pharmacol Exp Ther. 1974 May;189(2):499–512. [PubMed] [Google Scholar]
  24. 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]
  25. Maeno T. Analysis of sodium and potassium conductances in the procaine end-plate potential. J Physiol. 1966 Apr;183(3):592–606. doi: 10.1113/jphysiol.1966.sp007886. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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]
  27. 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]
  28. 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]
  29. Norman R. S. Non-linear dose-response relation at the frog neuromuscular junction. Brain Res. 1975 Jun 6;90(1):164–168. doi: 10.1016/0006-8993(75)90693-9. [DOI] [PubMed] [Google Scholar]
  30. Rang H. P. Drug receptors and their function. Nature. 1971 May 14;231(5298):91–96. doi: 10.1038/231091a0. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. 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]
  33. 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]

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

RESOURCES