Mutations in the channel domain alter desensitization of a neuronal nicotinic receptor.
Nature. 1991-10-01; 353(6347): 846-849
DOI: 10.1038/353846a0
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1. Nature. 1991 Oct 31;353(6347):846-9.
Mutations in the channel domain alter desensitization of a neuronal nicotinic
receptor.
Revah F(1), Bertrand D, Galzi JL, Devillers-Thiéry A, Mulle C, Hussy N, Bertrand
S, Ballivet M, Changeux JP.
Author information:
(1)Neurobiologie Moléculaire, Unité de Recherche Associée au Centre National de
la Recherche Scientifique, Institut Pasteur, Paris, France.
A variety of ligand-gated ion channels undergo a fast activation process after
the rapid application of agonist and also a slower transition towards
desensitized or inactivated closed channel states when exposure to agonist is
prolonged. Desensitization involves at least two distinct closed states in the
acetylcholine receptor, each with an affinity for agonists higher than those of
the resting or active conformations. Here we investigate how structural elements
could be involved in the desensitization of the acetylcholine-gated ion channel
from the chick brain alpha-bungarotoxin sensitive homo-oligomeric alpha 7
receptor, using site-directed mutagenesis and expression in Xenopus oocytes.
Mutations of the highly conserved leucine 247 residue from the uncharged MII
segment of alpha 7 suppress inhibition by the open-channel blocker QX-222,
indicating that this residue, like others from MII, faces the lumen of the
channel. But, unexpectedly, the same mutations decrease the rate of
desensitization of the response, increase the apparent affinity for acetylcholine
and abolish current rectification. Moreover, unlike wild-type alpha 7, which has
channels with a single conductance level, the leucine-to-threonine mutant has an
additional conducting state active at low acetylcholine concentrations. It is
possible that mutation of Leu 247 renders conductive one of the high-affinity
desensitized states of the receptor.
DOI: 10.1038/353846a0
PMID: 1719423 [Indexed for MEDLINE]