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Science 16 December 1988:
Vol. 242. no. 4885, pp. 1578 - 1581
DOI: 10.1126/science.2462281
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Articles

Science, Vol 242, Issue 4885, 1578-1581
Copyright © 1988 by American Association for the Advancement of Science

articles

Evidence that the M2 membrane-spanning region lines the ion channel pore of the nicotinic receptor

RJ Leonard, CG Labarca, P Charnet, N Davidson, and HA Lester

Division of Biology, California Institute of Technology, Pasadena 91125.

Site-directed mutagenesis and expression in Xenopus oocytes were used to study acetylcholine receptors in which serine residues (i) were replaced by alanines (alpha, delta subunits) or (ii) replaced a phenylalanine (beta subunit) at a postulated polar site within the M2 transmembrane helix. As the number of serines decreased, there were decreases in the residence time and consequently the equilibrium binding affinity of QX-222, a quaternary ammonium anesthetic derivative thought to bind within the open channel. Receptors with three serine-to-alanine mutations also displayed a selective decrease in outward single-channel currents. Both the direction of this rectification and the voltage dependence of QX-222 blockade suggest that the residues mutated are within the aqueous pore of the receptor and near its cytoplasmic (inner) surface.


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