S. Bohler et al., Desensitization of neuronal nicotinic acetylcholine receptors conferred byN-terminal segments of the beta 2 subunit, BIOCHEM, 40(7), 2001, pp. 2066-2074
Desensitization is a general property of ligand-gated ion channels. Because
of a wide array of available subunit combinations, it generates different
time constants for channel closure, thereby modulating the processing of in
formation in the brain. Within the family of neuronal nicotinic acetylcholi
ne receptors (nAChRs), alpha3 beta2 and alpha3 beta4 receptors display cont
rasting properties of desensitization. When measured using two-electrode vo
ltage-clamp in Xenopus oocytes, desensitization results in current decrease
s 2 s after initiation of acetylcholine application by 94% for alpha3 beta2
receptors, but only by 6% in the case of alpha3 beta4 receptors. Desensiti
zation was analyzed by inserting different portions of the beta2 into the b
eta4 subunit. Residues 1-212 of the beta2 subunit were able to confer 78% d
esensitization in 2 s, while smaller chimeras revealed desensitization in 2
s conferred by residues 1-42 alone to a level of 50%, by residues 72-89 to
a level of 74%, and by residues 96-212 to a level of 77%. Some long-term (
25 min) effects of desensitization driven by acetylcholine were found to re
ly partially on the same elements, including an enhancement mediated by res
idues 1-95 and 96-212 of the beta2 subunit individually. Our results reveal
that desensitization relies independently on diverse portions of the extra
cellular domain of the beta2 subunit. Phenotype of alpha3 beta4 involves, i
n contrast, complex structural requirements involving residues dispersed th
roughout the entire N-terminal domain of the beta4 subunit.