SPONTANEOUS AND AGONIST-INDUCED OPENINGS OF AN ACETYLCHOLINE-RECEPTOR CHANNEL COMPOSED OF BOVINE MUSCLE ALPHA-SUBUNIT, BETA-SUBUNIT AND DELTA-SUBUNIT

SPONTANEOUS AND AGONIST-INDUCED OPENINGS OF AN ACETYLCHOLINE-RECEPTOR CHANNEL COMPOSED OF BOVINE MUSCLE ALPHA-SUBUNIT, BETA-SUBUNIT AND DELTA-SUBUNIT
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DOI:
10.1007/bf00370689
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发表时间:
1990-10-01
影响因子:
4.5
通讯作者:
SAKMANN, B
SAKMANN, B
中科院分区:
医学3区
文献类型:
--
作者:
JACKSON, MB;IMOTO, K;SAKMANN, B

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在哺乳动物肌肉的发育过程中,烟碱乙酰胆碱受体(AChR)的γ-亚基被ε-亚基取代,从而在通道的电导和门控方面产生明确的改变。为了更好地理解γ-和ε-亚基的功能作用,我们研究了缺乏这些亚基的AChR通道的特性。在注射了牛α-β-和δ-亚基特异性mRNA(称为α.β.δ-AChR)的非洲爪蟾卵母细胞中表达的AChR是不寻常的,因为其通道在不存在激动剂的情况下以高频率自发打开。通过比较α..β..δ-AChR与包含γ-或ε-亚基的完整受体,我们得出结论,γ-和ε-亚基影响大多数通道特性,包括激动剂结合,并且对于稳定未配体受体通道的闭合状态尤其重要。当注射一整套四个亚基特异性mRNA时,可以形成.alpha..beta..delta.-AChR。其组装的容易性增加了α..β..δ-AChR导致发育过程中发生的受体特性的一些变化的可能性。
During the development of mammalian muscle they .gamma.-subunit of the nicotinic acetylcholine receptor (AChR) is replaced by the .epsilon.-subunit to produce well-defined alterations in the conductance and gating of the channel. To gain a better understanding of the functional role of the .gamma.- and .epsilon.-subunits, we have studied the properties of an AChR channel lacking these subunits. The AChR expressed in Xenopus oocytes injected with the bovine .alpha.- .beta.- and .delta.-subunit-specific mRNAs (referred to as .alpha..beta..delta.-AChR) is unusual in that its channel opens spontaneously at a high frequency in the absence of agonist. From a comparison of the .alpha..beta..delta.-AChR with complete receptors containing either the .gamma.-or .epsilon.-subunit, we conclude that the .gamma.- and .epsilon.-subunits influence most channel properties, including agonist binding, and are especially important for stabilizing the closed state of the unliganded receptor channel. The .alpha..beta..delta.-AChR can form when a complete set of four subunit-specific mRNAs is injected. The ease with which it is assembled raises the possibility that the .alpha..beta..delta.-AChR contributes to some of the variations in receptor properties that occur during development.