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Molecular Structure, Gating, and Regulation

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Nicotinic Receptors

Part of the book series: The Receptors ((REC,volume 26))

Abstract

Gating of ion channels is the opening response of the channel to a stimulus and its subsequent desensitization or inactivation. For nicotinic acetylcholine receptors, the stimulus is the binding of the neurotransmitter acetylcholine to an extracellular domain followed by a sequence of conformational changes resulting in rapid channel opening. In most channels a persistent stimulus invokes a second gating event driving the channel into an inactive, desensitized state that may or may not contribute to the net response. A full understanding of gating requires a correlation of structural changes with the kinetics of channel opening and desensitization; an understanding of how these changes result in rapid, large changes in ion flux through the channel; and how they are terminated. In this article the current structural changes and the current understanding of nicotinic receptor channel kinetics are reviewed and correlated. The analysis necessarily draws on inferences from the larger family of ligand-gated ion channels and related proteins. The focus will be predominantly on the opening event but will also include consideration of desensitization.

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Abbreviations

AChBP:

Acetylcholine Binding Protein

ELIC:

Erwinia chrysanthemi ligand-gated ion channel

GLIC:

Gloeobacter violaceus ligand-gated ion channel

Glu-Cl:

C. elegans glutamate-gated chloride channel

LFER:

Linear free energy relationship

LGIC:

Pentameric ligand-gated ion channel

MWC:

Monod-Wyman-Changeux cooperativity model

nAChR:

Nicotinic acetylcholine receptor

TID:

3-(trifluoromethyl)-3-(m-iodophenyl)diazirine

TM:

Transmembrane domain

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Acknowledgements

All molecular modeling figures were created using VMD [82].

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Correspondence to Steen E. Pedersen Ph.D. .

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Pedersen, S.E. (2014). Molecular Structure, Gating, and Regulation. In: Lester, R. (eds) Nicotinic Receptors. The Receptors, vol 26. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1167-7_2

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