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Sci. STKE, 2 September 2003
[DOI: 10.1126/scisignal.1982003tr2]

A Speculative Model of AChR gating at the Frog Neuromuscular Junction

Anthony Auerbach*

Center for Single Molecule Biophysics, State University of New York at Buffalo, Buffalo, NY 14214, USA.

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*Corresponding author. E-mail: auerbach{at}buffalo.edu

Description

The animation depicts a speculative model of nicotinic acetylcholine receptor (AChR) gating at the frog neuromuscular junction. Following a nerve impulse, the neurotransmitter acetylcholine (ACh) is released from synaptic vesicles docked at the active zone of the presynaptic nerve terminal. ACh diffuses across the synaptic cleft to bind to AChRs, ligand-gated channels found at the lips of the postjunctional folds of the muscle, initiating gating, a conformational change that allows ions to flow through the channel and thereby elicit an electrical response in the muscle (the end-plate potential). In the AChR, gating involves a series of small conformational changes that propagate throughout the channel as it moves from "closed" to "open," rather than a synchronous switch in protein configuration.

Each AChR is a pentamer containing two alpha subunits, a β subunit, a δ subunit, and either a γ or ε subunit.

In the depiction of gating, the structure is from acetylcholine binding protein (a homolog of the extracellular domain of the AChR) in the extracellular domain and represents the M4 (straight) and M2 (kinked) segments of the acetylcholine receptor alpha subunit (left) and δ subunit (right) in the membrane domain. The small circles represent residues whose effects on gating have been probed by mutations. Residues that remain gray represent sites where mutations do not affect gating; residues that are blue represent sites where mutations result in no expression or no gating; residues that are brown represent sites where mutations have effects that prevent the estimation of their effect on gating. The sequence of movements depicted for the residues that turn yellow depends upon experimental measurements in which point mutations were made to individual AChR residues and the ensuing changes in the rate constants of channel opening and closing were determined.

Click the green arrows to proceed through the animation.

This animation was based on Animation 1, A Speculative Model of Gating in the nAChR, from the Review by Auerbach (see below) and was adapted by Cameron Slayden from an animation by R. Foxenberg under the scientific oversight of A. Auerbach, Center for Single Molecule Biophysics, State University of New York at Buffalo, Buffalo, NY 14214, USA.

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Educational Details

Learning Resource Type: Animation

Context: Undergraduate upper division, graduate, professional (degree program)

Intended Users: Teacher, learner

Intended Educational Use: Teach, learn

Discipline: Biophysics, physiology, structural biology

Keywords: movie, nicotinic acetylcholine receptor, gating, synapse, frog, neuromuscular junction, signal transduction

Technical Details

Format: Shockwave Flash Object (swf file)

Size: 478 kb

Requirements: Macromedia Flash 5 (http://www.macromedia.com/downloads/)

Related Resources

Review: A. Auerbach, Life at the top: The transition state of AChR gating. Sci. STKE 2003, re11 (2003). [Gloss] [Abstract] [Full Text]

ST on the Web: Educator Sites (http://stke.sciencemag.org/cgi/ul/sigtransUl;CAT_9)--BioSciEdNet (BEN) Portal

Limits for Use

Cost: Free

Rights: This material may be downloaded, printed, linked to, and/or redistributed without modification for non-commercial, course teaching purposes only, provided credit to STKE is included by listing the citation for the teaching resource.

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Citation: A. Auerbach, A speculative model of AChR gating at the frog neuromuscular junction. Sci. STKE 2003, tr2 (2003).

© 2003 American Association for the Advancement of Science

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