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Tris+/Na+ permeability ratios of nicotinic acetylcholine receptors are reduced by mutations near the intracellular end of the M2 region

Cohen, Bruce N. and Labarca, Cesar and Czyzyk, Linda and Davidson, Norman and Lester, Henry A. (1992) Tris+/Na+ permeability ratios of nicotinic acetylcholine receptors are reduced by mutations near the intracellular end of the M2 region. Journal of General Physiology, 99 (4). pp. 545-572. ISSN 0022-1295. http://resolver.caltech.edu/CaltechAUTHORS:COHjgp92b

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Abstract

Tris+/Na+ permeability ratios were measured from shifts in the biionic reversal potentials of the macroscopic ACh-induced currents for 3 wild- type (WT), 1 hybrid, 2 subunit-deficient, and 25 mutant nicotinic receptors expressed in Xenopus oocytes. At two positions near the putative intracellular end of M2, 2' (alpha Thr244, beta Gly255, gamma Thr253, delta Ser258) and -1', point mutations reduced the relative Tris+ permeability of the mouse receptor as much as threefold. Comparable mutations at several other positions had no effects on relative Tris+ permeability. Mutations in delta had a greater effect on relative Tris+ permeability than did comparable mutations in gamma; omission of the mouse delta subunit (delta 0 receptor) or replacement of mouse delta with Xenopus delta dramatically reduced relative Tris+ permeability. The WT mouse muscle receptor (alpha beta gamma delta) had a higher relative permeability to Tris+ than the wild-type Torpedo receptor. Analysis of the data show that (a) changes in the Tris+/Na+ permeability ratio produced by mutations correlate better with the hydrophobicity of the amino acid residues in M2 than with their volume; and (b) the mole-fraction dependence of the reversal potential in mixed Na+/Tris+ solutions is approximately consistent with the Goldman- Hodgkin-Katz voltage equation. The results suggest that the main ion selectivity filter for large monovalent cations in the ACh receptor channel is the region delimited by positions -1' and 2' near the intracellular end of the M2 helix.


Item Type:Article
Additional Information:Copyright © 1992 by The Rockefeller University Press. RUP grants the public the non-exclusive right to copy, distribute, or display the Work under a Creative Commons Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/ and http://creativecommons.org/licenses/by-nc-sa/3.0/legalcode. Original version received 19 July 1991 and accepted version received 13 December 1991. We thank Euk Kwon and Michael Quick for technical assistance, Fred Sigworth and Gary Yellen for helpful discussion, and Pierre Charnet for much tutelage and helpful discussion. This research was supported by grants from the National Institutes of Health (NS-11756) and the Muscular Dystrophy Association.
Record Number:CaltechAUTHORS:COHjgp92b
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:COHjgp92b
Alternative URL:http://www.jgp.org/cgi/content/abstract/99/4/545
Usage Policy:RUP grants the public the non-exclusive right to copy, distribute, or display the Work under a Creative Commons Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/ and http://creativecommons.org/licenses/by-nc-sa/3.0/legalcode.
ID Code:10847
Collection:CaltechAUTHORS
Deposited By: Archive Administrator
Deposited On:13 Jun 2008
Last Modified:26 Dec 2012 10:05

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