Evidence for the exclusive expression of functional homomeric α7 nAChRs in hypothalamic histaminergic tuberomammillary neurons in rats.
Evidence for the exclusive expression of functional homomeric α7 nAChRs in hypothalamic histaminergic tuberomammillary neurons in rats.
复制标题
大鼠下丘脑组胺能结节乳头神经元功能性同聚α7 nAChR 的独家表达的证据。
DOI：
10.1016/j.neulet.2014.01.047
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发表时间：
2014
影响因子：
2.5
通讯作者：
Uteshev,VictorV
中科院分区：
文献类型：
--
作者：
Tischkau,Shelley;Mhaskar,Yashanad;Uteshev,VictorV
大鼠下丘脑组胺能结节乳头（TM）神经元表达高密度的烟碱乙酰胆碱受体（nAChRs），其Ca 2+渗透性、动力学和药理学性质与异源同型α7 nAChRs相似。然而，天然α7 nAChR亚基可以与β或α5 nAChR亚基共组装形成功能性异聚体α7-含有α7β或α7α5 nAChR，其动力学和药理学与α7同聚体相似。因此，尽管TM nAChR已被用作功能性α7同聚体的非体外模型，但TM nAChR的分子组成尚未确定，也未排除TM神经元中含功能性α7异聚体的表达。为了确定TM nAChR亚基转录本的概况，我们使用大鼠中急性分离的TM神经元进行了单细胞qRT-PCR实验。TM神经元只表达主要的α3、α6和α7 nAChR亚单位的转录本。未检测到其他已知哺乳动物神经元亚基（α2、α4-5、α9-10、β2-4）的转录本。在缺乏β和α5亚基的情况下，TM神经元中含有功能性α7的异聚体的表达是极不可能的，因为已知主要的α3、α6和α7 nAChR亚基单独不形成功能性异聚nAChR。这些结果支持大鼠TM神经元中天然功能性α7同聚体的排他性表达，并将这些神经元作为天然功能性同聚体α7 nAChR的独特可靠来源，适用于开发选择性α7 nAChR药物的体内和体外药理学测定。
Hypothalamic histaminergic tuberomammillary (TM) neurons in rats express high densities of nicotinic acetylcholine receptors (nAChRs) whose Ca2+permeability, kinetic and pharmacological properties are similar to those of heterologous homomeric α7 nAChRs. However, native α7 nAChR subunits can co-assemble with β or α5 nAChR subunits to form functional heteromeric α7-containing α7β or α7α5 nAChRs with kinetics and pharmacology similar to those of α7 homomers. Therefore, although TM nAChRs have been used as anex vivomodel of functional α7 homomers, the molecular makeup of TM nAChRs has not been determined and the expression of functional α7-containing heteromers in TM neurons has not been excluded. To determine the profile of TM nAChR subunit transcripts, we have conducted single-cell qRT-PCR experiments using acutely dissociated TM neurons in rats. TM neurons were found to express transcripts of only principal α3, α6 and α7 nAChR subunits. Transcripts of other known mammalian neuronal subunits (α2, α4–5, α9–10, β2–4) were not detected. In the absence of β and α5 subunits, the expression of functional α7-containing heteromers in TM neurons is highly unlikely because principal α3, α6 and α7 nAChR subunits alone are not known to form functional heteromeric nAChRs. These results support the exclusive expression of native functional α7 homomers in rat TM neurons and introduce these neurons as a unique reliable source of native functional homomeric α7 nAChRs suitable forex vivoandin vitropharmacological assays in developing selective α7 nAChR agents.