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α9α10 乙酰胆碱受体:一种非神经元烟碱型受体。

The α9α10 acetylcholine receptor: A non-neuronal nicotinic receptor.

作者信息

Elgoyhen Ana Belén

机构信息

Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres" (INGEBI), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Vuelta de Obligado 2490, Buenos Aires 1428, Argentina.

出版信息

Pharmacol Res. 2023 Apr;190:106735. doi: 10.1016/j.phrs.2023.106735. Epub 2023 Mar 15.

Abstract

Within the superfamily of pentameric ligand-gated ion channels, cholinergic nicotinic receptors (nAChRs) were classically identified to mediate synaptic transmission in the nervous system and the neuromuscular junction. The α9 and α10 nAChR subunits were the last ones to be identified. Surprisingly, they do not fall into the dichotomic neuronal/muscle classification of nAChRs. They assemble into heteropentamers with a well-established function as canonical ion channels in inner ear hair cells, where they mediate central nervous system control of auditory and vestibular sensory processing. The present review includes expression, pharmacological, structure-function, molecular evolution and pathophysiological studies, that define receptors composed from α9 and α10 subunits as distant and distinct members within the nAChR family. Thus, although α9 and α10 were initially included within the neuronal subdivision of nAChR subunits, they form a distinct clade within the phylogeny of nAChRs. Following the classification of nAChR subunits based on their main synaptic site of action, α9 and α10 should receive a name in their own right.

摘要

在五聚体配体门控离子通道超家族中,胆碱能烟碱受体(nAChRs)传统上被认为介导神经系统和神经肌肉接头处的突触传递。α9和α10 nAChR亚基是最后被鉴定出来的。令人惊讶的是,它们并不属于nAChRs的神经元/肌肉二分法分类。它们组装成异五聚体,在内耳毛细胞中作为典型离子通道具有明确的功能,在那里它们介导中枢神经系统对听觉和前庭感觉处理的控制。本综述包括表达、药理学、结构功能、分子进化和病理生理学研究,这些研究将由α9和α10亚基组成的受体定义为nAChR家族中遥远且独特的成员。因此,尽管α9和α10最初被归入nAChR亚基的神经元亚类,但它们在nAChRs的系统发育中形成了一个独特的分支。根据nAChR亚基基于其主要突触作用位点的分类,α9和α10应该有它们自己独立的名称。

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