Modulation of recombinant, α2*, α3* or α4*-nicotinic acetylcholine receptor (nAChR) function by nAChR β3 subunits.
Modulation of recombinant, α2*, α3* or α4*-nicotinic acetylcholine receptor (nAChR) function by nAChR β3 subunits.
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DOI：
10.1111/j.1471-4159.2012.07685.x
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发表时间：
2012-05
影响因子：
4.7
通讯作者：
Lukas RJ
中科院分区：
文献类型：
--
作者：
Dash B;Bhakta M;Chang Y;Lukas RJ
烟碱乙酰胆碱受体（nAChR）β3亚基被认为在涉及药物依赖和奖赏的多巴胺能区域中表达的nAChR亚型中起辅助作用。当β3亚基过量表达时，它们对选定的nAChR亚型的功能具有显性负效应。在这项研究中，我们发现，在表达α2，α3或α4加上β2或β4亚基的非洲爪蟾卵母细胞中，在假定存在类似数量的每个nAChR亚基的情况下，与野生型β3亚基共表达通常（除α3*-nAChR外）使激动剂诱发的内向峰电流的幅度降低20-50%，而对激动剂效力没有显著影响（≤ 2倍）。相比之下，与突变体β 3 V9'S亚基的共表达通常（除了α4β2*-nAChR）增加激动剂效力，与预期的功能获得效应一致。这最戏剧性地证明了含有三种亚基的复合物的形成。此外，对于表达含有任何α亚基加β4和β 3V 9'S亚基的nAChR的卵母细胞，存在对开放通道阻断剂阿托品阻断敏感的自发通道开放。总的来说，结果表明β3亚基整合到所有研究的受体组件中，并表明与β3亚基的天然共表达可以影响几种nAChR亚型的表达水平和激动剂敏感性。
The nicotinic acetylcholine receptor (nAChR) β3 subunit is thought to serve an accessory role in nAChR subtypes expressed in dopaminergic regions implicated in drug dependence and reward. When β3 subunits are expressed in excess, they have a dominant-negative effect on function of selected nAChR subtypes. In this study, we show, in Xenopus oocytes expressing α2, α3 or α4 plus either β2 or β4 subunits, that in the presumed presence of similar amounts of each nAChR subunit, co-expression with wild-type β3 subunits generally (except for α3*-nAChR) lowers amplitudes of agonist-evoked, inward peak currents by 20–50% without having dramatic effects (≤ 2-fold) on agonist potencies. By contrast, co-expression with mutant β3V9'S subunits generally (except for α4β2*-nAChR) increases agonist potencies, consistent with an expected gain-of-function effect. This most dramatically demonstrates formation of complexes containing three kinds of subunit. Moreover, for oocytes expressing nAChR containing any α subunit plus β4 and β3V9'S subunits, there is spontaneous channel opening sensitive to blockade by the open channel blocker, atropine. Collectively, the results indicate that β3 subunits integrate into all of the studied receptor assemblies and suggest that natural co-expression with β3 subunits can influence levels of expression and agonist sensitivities of several nAChR subtypes.
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