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Determinants of Nicotinic Receptor Gating in Natural and Unnatural Side Chain Structures at the M2 9′ Position

Kearney, Patrick C. and Zhang, Haiyun and Zhong, Wenge and Dougherty, Dennis A. and Lester, Henry A. (1996) Determinants of Nicotinic Receptor Gating in Natural and Unnatural Side Chain Structures at the M2 9′ Position. Neuron, 17 (6). pp. 1221-1229. ISSN 0896-6273. doi:10.1016/s0896-6273(00)80252-4.

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A nonsense suppression method was employed to incorporate a total of four natural and six unnatural residues at the 9′ position of the M2 region in the β, γ, and δ subunits of muscle nicotinic receptors. In 33 pairwise comparisons of functional properties as influenced by structural features including side chain length, branching, and substitution of oxygen for methylene carbons, it is concluded that increased polarity in the side chains at the 9′ position consistently increases the sensitivity to acetylcholine. In addition, the stereochemistry of the side chain can have marked influences on the EC₅₀, primarily because of changes in the single-channel open time. For the case of isoleucine versus allo-isoleucine in the δ subunit, these changes are themselves modified by mutations at the 9′ position in other subunits. The data suggest an especially strong interaction between the β and δ subunits in the pore region, leading in turn to a suggested arrangement of subunits within the pentamer.

Item Type:Article
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Dougherty, Dennis A.0000-0003-1464-2461
Lester, Henry A.0000-0002-5470-5255
Additional Information:© 1996 Cell Press. Published by Elsevier Inc. Received 13 September 1996, Revised 16 October 1996. We thank Brad Henkle for help with oocytes and H. Dang, P. England, C. Labarca, M. Nowak, M. E. Saks, J. Sampson, S. Silverman, and Y. Zhang for comments. This work was supported by the National Institutes of Health (NS34407 and NS11756), by the California Tobacco-Related Disease Research Program, and by the Beckman Institute at Caltech. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 USC Section 1734 solely to indicate this fact.
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California Tobacco-Related Disease Research ProgramUNSPECIFIED
Caltech Beckman InstituteUNSPECIFIED
Issue or Number:6
Record Number:CaltechAUTHORS:20200518-070216780
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Official Citation:Patrick C Kearney, Haiyun Zhang, Wenge Zhong, Dennis A Dougherty, Henry A Lester, Determinants of Nicotinic Receptor Gating in Natural and Unnatural Side Chain Structures at the M2 9′ Position, Neuron, Volume 17, Issue 6, 1996, Pages 1221-1229, ISSN 0896-6273, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:103252
Deposited By: Tony Diaz
Deposited On:18 May 2020 16:20
Last Modified:16 Nov 2021 18:19

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