A. Camposcaro et al., ROLE OF THE PUTATIVE TRANSMEMBRANE SEGMENT M3 IN GATING OF NEURONAL NICOTINIC RECEPTORS, Biochemistry, 36(9), 1997, pp. 2709-2715
The involvement of some structural domains in the gating of the neuron
al nicotinic acetylcholine receptor (AChR) was studied by expressing f
unctional alpha 7/alpha 3 chimeric subunits in Xenopus oocytes. Substi
tution of the M3 transmembrane segment in the alpha 7 subunit modifies
the kinetic properties of the chimeric AChRs as follows: (a) a 6-fold
reduction in the maximal current evoked by nicotinic agonists, (b) a
10-fold decrease in the macroscopic desensitization rate, (c) an incre
ase of almost 1 order of magnitude in the apparent affinity for acetyl
choline and nicotine, and (d) a decrease in the affinity for alpha-bun
garotoxin. Computer simulations showed that the first three effects co
uld be accounted for by a simple kinetic model in which chimeric AChRs
presented a smaller ratio of the gating rates, beta/alpha, and a slig
htly slower desensitization rate. It is concluded that the M3 domain i
nfluences the gating of neuronal AChRs.