α3β4 subunit-containing nicotinic receptors dominate function in rat medial habenula neurons
α3β4 subunit-containing nicotinic receptors dominate function in rat medial habenula neurons
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DOI：
10.1016/s0028-3908(99)00024-6
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发表时间：
1999-06-01
影响因子：
4.7
通讯作者：
Lester, RAJ
中科院分区：
文献类型：
--
作者：
Quick, MW;Ceballos, RM;Lester, RAJ
采用全细胞膜片钳技术在大鼠内侧缰核（MHb）脑片上研究了烟碱乙酰胆碱受体（nAChRs）的区域特异性差异。腹侧三分之二的MHb中的大多数细胞对nAChR激动剂的局部压力应用作出强烈反应。在中间和腹侧三分之一的MHb的平均激动剂效力概况是相似的：野靛碱是最有效的激动剂和DMPP最弱的，与在MHb的所有区域中β 4亚基对功能性nAChR的显著贡献一致。在急性分离的MHb神经元中，α 3 β 4-选择性毒素α-CTx-AuIB（1 μ M）可逆地阻断了约75%的尼古丁诱导电流，正如仅表达α 3 β 4 nAChR的细胞所预期的那样。然而，α 3 β 2-选择性毒素α-CTx-MII（100 nM）阻断了MHb烟碱反应的可变部分（0-90%），这意味着β 2亚基可能有助于某些功能性受体。我们认为，α-CTx-MII的影响可能是由于与α 3 β 2 β 4亚基的nAChR相互作用引起的。这一观点得到以下发现的支持：（1）α-CTx-MII拮抗非洲爪蟾卵母细胞中由α 3、β 2和β 4亚基组成的受体，以及（2）突变型α-CTx-MII毒素[H12 A]（其阻断α 3 β 2 β 4受体但不阻断α 3 β 2或α 3 β 4 nAChR）也降低某些MHb神经元中的烟碱电流。总的来说，这些数据意味着MHb细胞上的大多数功能性nAChR至少含有α 3和β 4亚基，并且可变亚群还含有β 2亚基。(C)1999 Elsevier Science Ltd.保留所有权利。
Regional-specific differences in nicotinic acetylcholine receptors (nAChRs) were examined using the whole-cell patch clamp technique in rat medial habenula (MHb) slices. The majority of cells in the ventral two thirds of the MHb responded robustly to local pressure application of nAChR agonists. Mean agonist potency profiles in the middle and ventral thirds of the MHb were similar: cytisine was the most potent agonist and DMPP the weakest, consistent with a significant contribution of the beta 4 subunit to functional nAChRs in all areas of the MHb. In acutely isolated MHb neurons, the alpha 3 beta 4-selective toxin alpha-CTx-AuIB (1 mu M) reversibly blocked approximate to 75% of the nicotine-induced currents, as expected for cells solely expressing alpha 3 beta 4 nAChRs. However, the alpha 3 beta 2-selective toxin, alpha-CTx-MII (100 nM), blocked a variable fraction (0-90%) of the MHb nicotinic response implying that beta 2 subunits may contribute to some functional receptors. We suggest that the effects of alpha-CTx-MII may arise from interaction with alpha 3 beta 2 beta 4 subunit-containing nAChRs. This idea is supported by the findings (1) that alpha-CTx-MII antagonizes receptors comprised of alpha 3, beta 2 and beta 4 subunits in Xenopus oocytes, and (2) that a mutant alpha-CTx-MII toxin[H12A], which blocks alpha 3 beta 2 beta 4 receptors but not alpha 3 beta 2 or alpha 3 beta 4 nAChRs, also reduces nicotinic currents in some MHb neurons. Overall these data imply that most functional nAChRs on MHb cells contain at least alpha 3 and beta 4 subunits, and that a variable subpopulation additionally contains the beta 2 subunit. (C) 1999 Elsevier Science Ltd. All rights reserved.