Edelstein-Biol-Cybern-1996-Nicotinic-excitation.omex
title: Nicotinic excitatory post-synaptic potential (Edelstein et al., Biol Cybern, 1996)
abstract: Model of a nicotinic Excitatory Post-Synaptic Potential in a Torpedo electric organ. Acetylcholine is represented explicitely as a molecular species.
keyword: Ion Channel Gating
keyword: Membrane Potentials
keyword: Receptors, Nicotinic
keyword: Synapses
description: A kinetic model that links conformational interconversion rates to agonist binding and extends the general principles of the Monod-Wyman-Changeux model of allosteric transitions. The crucial assumption is that the linkage is controlled by the position of the interconversion transition states on a hypothetical linear reaction coordinate. Application of the model to the peripheral nicotine acetylcholine receptor (nAChR) accounts for the main properties of ligand-gating, including single-channel events, and several new relationships are predicted. Kinetic simulations reveal errors inherent in using the dose-response analysis, but justify its application under defined conditions. The model predicts that (in order to overcome the intrinsic stability of the B state and to produce the appropriate cooperativity) channel activation is driven by an A state with a Kd in the 50 nM range, hence some 140-fold stronger than the apparent affinity of the open state deduced previously. According to the model, recovery from the desensitized states may occur via rapid transit through the A state with minimal channel opening, thus without necessarily undergoing a distinct recovery pathway, as assumed in the standard 'cycle' model. Transitions to the desensitized states by low concentration 'pre-pulses' are predicted to occur without significant channel opening, but equilibrium values of IC50 can be obtained only with long pre-pulse times. Predictions are also made concerning allosteric effectors and their possible role in coincidence detection.
has taxon: Tetronarce californica
  identifier: http://identifiers.org/taxonomy/7787
encodes: neuromuscular synaptic transmission
  identifier: GO:0007274
encodes: transmission of nerve impulse
  identifier: GO:0019226
encodes: cell surface receptor signaling pathway
  identifier: GO:0007166
is: biomodels.db:BIOMD0000000002
  identifier: biomodels.db:BIOMD0000000002
creator: Stuart J. Edelstein
creator: Olivier Schaad
creator: Eric Henry
creator: Daniel Bertrand
creator: Jean-Pierre Changeux
contributor: Nicolas Le Novère
contributor: Jonathan Karr
  account name: https://orcid.org/0000-0001-8254-4958
  identifier: orcid:0000-0001-8254-4958
is described by:
  identifier: s004220050302
  label: Edelstein SJ, Schaad O, Henry E, Bertrand D & Changeux JP. A kinetic mechanism for nicotinic acetylcholine receptors based on multiple allosteric transitions. Biological cybernetics 1996, 75 (11): 361-379.
license: CC0-1.0
  identifier: spdx:CC0-1.0
created:
  W3 CDTF: 1996-11-01
modified: 2021-07-06

Figure 4b.vg.json
is: Figure 4b
  identifier: s004220050302

Figure 4b
is: Figure 4b
  identifier: s004220050302