Desensitization of neuronal nicotinic acetylcholine receptors conferred by N-terminal segments of the β2 subunit

被引:33
作者
Bohler, S
Gay, S
Bertrand, S
Corringer, PJ
Edelstein, SJ
Changeux, JP [1 ]
Bertrand, D
机构
[1] Inst Pasteur, URA CNRS 2182 Neurbiol Mol, Paris, France
[2] Ctr Med Univ Geneva, Dept Physiol, CH-1211 Geneva, Switzerland
[3] Univ Geneva, Dept Biochim, CH-1211 Geneva 4, Switzerland
关键词
D O I
10.1021/bi0020022
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 information in the brain. Within the family of neuronal nicotinic acetylcholine receptors (nAChRs), alpha3 beta2 and alpha3 beta4 receptors display contrasting properties of desensitization. When measured using two-electrode voltage-clamp in Xenopus oocytes, desensitization results in current decreases 2 s after initiation of acetylcholine application by 94% for alpha3 beta2 receptors, but only by 6% in the case of alpha3 beta4 receptors. Desensitization was analyzed by inserting different portions of the beta2 into the beta4 subunit. Residues 1-212 of the beta2 subunit were able to confer 78% desensitization 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 rely partially on the same elements, including an enhancement mediated by residues 1-95 and 96-212 of the beta2 subunit individually. Our results reveal that desensitization relies independently on diverse portions of the extracellular domain of the beta2 subunit. Phenotype of alpha3 beta4 involves, in contrast, complex structural requirements involving residues dispersed throughout the entire N-terminal domain of the beta4 subunit.
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页码:2066 / 2074
页数:9
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