An Analysis of the Dose-response Relationship at Voltage-clamped Frog Neuromuscular Junctions

Overview

Journal J Physiol

Specialty Physiology

Date 1978 Aug 1

PMID 309004

Citations 61

Authors

V E Dionne

J H Steinbach

C F Stevens

Affiliations

Soon will be listed here.

Abstract

1. Frog neuromuscular junctions were viewed with Nomarski optics and voltage clamped. Agonist was applied ionophoretically and agonist concentrations were measured using a micro-electrode sensitive to quaternary amines. 2. The dose-response relationship was studied using the agonists carbamylcholine, suberyldicholine and hydroxyphenyl-propyltrimethylammonium. 3. With all of these agonists, it appeared that the ACh receptor could be active when either one or two agonist binding sites were occupied. The receptor was much more likely to be active when both sites were occupied. Agonist dissociation constants and receptor activation probabilities were estimated by non-linear regression techniques for several possible receptor activation schemes.

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References

Purves R . The time course of cellular responses to iontophoretically applied drugs. J Theor Biol. 1977; 65(2):327-44. DOI: 10.1016/0022-5193(77)90328-9. View

KUFFLER S, Yoshikami D . The distribution of acetylcholine sensitivity at the post-synaptic membrane of vertebrate skeletal twitch muscles: iontophoretic mapping in the micron range. J Physiol. 1975; 244(3):703-30. PMC: 1330831. DOI: 10.1113/jphysiol.1975.sp010821. View

Magleby K, Terrar D . 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; 244(2):467-95. PMC: 1330772. DOI: 10.1113/jphysiol.1975.sp010808. View

Hartzell H, KUFFLER S, Yoshikami D . Post-synaptic potentiation: interaction between quanta of acetylcholine at the skeletal neuromuscular synapse. J Physiol. 1975; 251(2):427-63. PMC: 1348437. DOI: 10.1113/jphysiol.1975.sp011102. View

Changeux J, Benedetti L, Bourgeois J, Brisson A, Cartaud J, Devaux P . Some structural properties of the cholinergic receptor protein in its membrane environmental relevant to its function as a pharmacological receptor. Cold Spring Harb Symp Quant Biol. 1976; 40:211-30. DOI: 10.1101/sqb.1976.040.01.023. View

Ruff R . A quantitative analysis of local anaesthetic alteration of miniature end-plate currents and end-plate current fluctuations. J Physiol. 1977; 264(1):89-124. PMC: 1307749. DOI: 10.1113/jphysiol.1977.sp011659. View

Colquhoun D . Mechanisms of drug action at the voluntary muscle endplate. Annu Rev Pharmacol. 1975; 15:307-25. DOI: 10.1146/annurev.pa.15.040175.001515. View

Adams P . Relaxation experiments using bath-applied suberyldicholine. J Physiol. 1977; 268(2):271-89. PMC: 1283664. DOI: 10.1113/jphysiol.1977.sp011857. View

Patrick J, McMillan J, WOLFSON H, OBrien J . Acetylcholine receptor metabolism in a nonfusing muscle cell line. J Biol Chem. 1977; 252(6):2143-53. View

10.

Sheridan R, Lester H . Rates and equilibria at the acetylcholine receptor of Electrophorus electroplaques: a study of neurally evoked postsynaptic currents and of voltage-jump relaxations. J Gen Physiol. 1977; 70(2):187-219. PMC: 2228462. View

11.

Dionne V . Characterization of drug iontophoresis with a fast microassay technique. Biophys J. 1976; 16(7):705-17. PMC: 1334895. DOI: 10.1016/S0006-3495(76)85723-2. View

12.

Beam K . A quantitative description of end-plate currents in the presence of two lidocaine derivatives. J Physiol. 1976; 258(2):301-22. PMC: 1308977. DOI: 10.1113/jphysiol.1976.sp011421. View

13.

Colquhoun D, Range H . Effects of inhibitors of the binding of iodinated alpha-bungarotoxin to acetylcholine receptors in rat muscle. Mol Pharmacol. 1976; 12(4):519-35. View

14.

Weber M, Changeux J . Regulation of binding properties of the nicotinic receptor protein by cholinergic ligands in membrane fragments from Torpedo marmorata. Proc Natl Acad Sci U S A. 1975; 72(9):3443-7. PMC: 433010. DOI: 10.1073/pnas.72.9.3443. View

15.

Sheridan R, Lester H . Relaxation measurements on the acetylcholine receptor. Proc Natl Acad Sci U S A. 1975; 72(9):3496-500. PMC: 433021. DOI: 10.1073/pnas.72.9.3496. View

16.

RAFTERY M, Vandlen R, Reed K, Lee T . Characterization of Torpedo californica acetylcholine receptor: its subunit composition and ligand-binding properties. Cold Spring Harb Symp Quant Biol. 1976; 40:193-202. DOI: 10.1101/sqb.1976.040.01.021. View

17.

Colquhoun D, Dionne V, Steinbach J, Stevens C . Conductance of channels opened by acetylcholine-like drugs in muscle end-plate. Nature. 1975; 253(5488):204-6. DOI: 10.1038/253204a0. View

18.

Dreyer F, Peper K . Acetylcholine receptor: modification of synaptic gating mechanism after treatment with a disulfide bond reducing agent. Pflugers Arch. 1975; 355(1):19-26. DOI: 10.1007/BF00584796. View

19.

Dionne V, Stevens C . Voltage dependence of agonist effectiveness at the frog neuromuscular junction: resolution of a paradox. J Physiol. 1975; 251(2):245-70. PMC: 1348425. DOI: 10.1113/jphysiol.1975.sp011090. View

20.

Neher E, Sakmann B . Single-channel currents recorded from membrane of denervated frog muscle fibres. Nature. 1976; 260(5554):799-802. DOI: 10.1038/260799a0. View