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Proc Natl Acad Sci U S A. Nov 1981; 78(11): 7200–7204.
PMCID: PMC349224

Kinetic parameters for acetylcholine interaction in intact neuromuscular junction.

Abstract

The dependency of miniature endplate current (mepc) rise time upon mepc amplitude and acetylcholine receptor site density was measured in lizard intercostal muscles and used to fit the rate constants in a simple kinetic scheme. The kinetic scheme included diffusion, two-step sequential binding of acetylcholine to receptor, and opening of the ion channel. Numerical simulation of the observed mepc behavior yielded the following kinetic constants; (i) diffusion constant, 4 X 10(-6) cm2 sec-1; (ii) forward binding rates, 4.7 X 10(7) M-1 sec-1; (iii) channel relaxation rate, 25 msec-1. The value above for the forward binding rates assumed both rates to be equal. If they are different, the slower of the two is in the range of 2-5 X 10(7) M-1 sec-1. A radial profile of bound receptor indicated that activation of the receptor was very local, occurring essentially within a radius of about 0.3 micrometers from the point of acetylcholine release.

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Selected References

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  • Land BR, Salpeter EE, Salpeter MM. Acetylcholine receptor site density affects the rising phase of miniature endplate currents. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3736–3740. [PMC free article] [PubMed]
  • Fertuck HC, Salpeter MM. Quantitation of junctional and extrajunctional acetylcholine receptors by electron microscope autoradiography after 125I-alpha-bungarotoxin binding at mouse neuromuscular junctions. J Cell Biol. 1976 Apr;69(1):144–158. [PMC free article] [PubMed]
  • Matthews-Bellinger J, Salpeter MM. Distribution of acetylcholine receptors at frog neuromuscular junctions with a discussion of some physiological implications. J Physiol. 1978 Jun;279:197–213. [PMC free article] [PubMed]
  • Wathey JC, Nass MM, Lester HA. Numerical reconstruction of the quantal event at nicotinic synapses. Biophys J. 1979 Jul;27(1):145–164. [PMC free article] [PubMed]
  • Hartzell HC, Kuffler SW, Yoshikami D. Post-synaptic potentiation: interaction between quanta of acetylcholine at the skeletal neuromuscular synapse. J Physiol. 1975 Oct;251(2):427–463. [PMC free article] [PubMed]
  • Adams PR. Relaxation experiments using bath-applied suberyldicholine. J Physiol. 1977 Jun;268(2):271–289. [PMC free article] [PubMed]
  • Neubig RR, Cohen JB. Equilibrium binding of [3H]tubocurarine and [3H]acetylcholine by Torpedo postsynaptic membranes: stoichiometry and ligand interactions. Biochemistry. 1979 Nov 27;18(24):5464–5475. [PubMed]
  • Neubig RR, Cohen JB. Permeability control by cholinergic receptors in Torpedo postsynaptic membranes: agonist dose-response relations measured at second and millisecond times. Biochemistry. 1980 Jun 10;19(12):2770–2779. [PubMed]
  • Sine SM, Taylor P. The relationship between agonist occupation and the permeability response of the cholinergic receptor revealed by bound cobra alpha-toxin. J Biol Chem. 1980 Nov 10;255(21):10144–10156. [PubMed]
  • Dionne VE, Steinbach JH, Stevens CF. An analysis of the dose-response relationship at voltage-clamped frog neuromuscular junctions. J Physiol. 1978 Aug;281:421–444. [PMC free article] [PubMed]
  • Sheridan RE, Lester HA. 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 Aug;70(2):187–219. [PMC free article] [PubMed]
  • Colquhoun D, Dionne VE, Steinbach JH, Stevens CF. Conductance of channels opened by acetylcholine-like drugs in muscle end-plate. Nature. 1975 Jan 17;253(5488):204–206. [PubMed]
  • Dionne VE. Characterization of drug iontophoresis with a fast microassay technique. Biophys J. 1976 Jul;16(7):705–717. [PMC free article] [PubMed]
  • Adams PR. Acetylcholine receptor kinetics. J Membr Biol. 1981 Feb 28;58(3):161–174. [PubMed]
  • Adler M, Albuquerque EX, Lebeda FJ. Kinetic analysis of end plate currents altered by atropine and scopolamine. Mol Pharmacol. 1978 May;14(3):514–529. [PubMed]
  • Grünhagen HH, Iwatsubo M, Changeux JP. Fast kinetic studies on the interaction of cholinergic agonists with the membrane-bound acetylcholine receptor from Torpedo marmorata as revealed by quinacrine fluorescence. Eur J Biochem. 1977 Oct 17;80(1):225–242. [PubMed]
  • Llinás R, Steinberg IZ, Walton K. Relationship between presynaptic calcium current and postsynaptic potential in squid giant synapse. Biophys J. 1981 Mar;33(3):323–351. [PMC free article] [PubMed]
  • Neumann E, Chang HW. Dynamic properties of isolated acetylcholine receptor protein: kinetics of the binding of acetylcholine and Ca ions. Proc Natl Acad Sci U S A. 1976 Nov;73(11):3994–3998. [PMC free article] [PubMed]
  • Kuffler SW, Yoshikami D. The number of transmitter molecules in a quantum: an estimate from iontophoretic application of acetylcholine at the neuromuscular synapse. J Physiol. 1975 Oct;251(2):465–482. [PMC free article] [PubMed]
  • Cash DJ, Aoshima H, Hess GP. Acetylcholine-induced cation translocation across cell membranes and inactivation of the acetylcholine receptor: chemical kinetic measurements in the millisecond time region. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3318–3322. [PMC free article] [PubMed]

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