β-amyloid peptide activates α7 nicotinic acetylcholine receptors expressed in Xenopus oocytes
β-amyloid peptide activates α7 nicotinic acetylcholine receptors expressed in Xenopus oocytes
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DOI：
10.1074/jbc.m200066200
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发表时间：
2002-07-12
影响因子：
4.8
通讯作者：
Sweatt, JD
中科院分区：
文献类型：
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作者：
Dineley, KT;Bell, KA;Sweatt, JD
α 7烟碱乙酰胆碱受体在海马和基底前脑的胆碱能投射神经元中高度表达，这些结构特别容易受到阿尔茨海默病的破坏。先前的工作表明β-淀粉样肽可以与α 7烟碱乙酰胆碱受体相互作用，尽管这种相互作用的性质尚未得到很好的表征。为了测试β-淀粉样肽是否可以激活α 7烟碱乙酰胆碱受体，我们在非洲爪蟾卵母细胞中表达了这些受体，并进行了双电极电压钳记录，表征了对β-淀粉样肽1-42的反应，其浓度范围为1 μ m至100 nM。在表达α 7的卵母细胞中，β-淀粉样蛋白肽1-42在低浓度（1-100 μ m）下激发内向电流，而在较高浓度（nM）下，观察到较不有效的受体激活，指示受体脱敏。与α 7选择性试剂、拮抗剂甲基利卡那汀和激动剂4-OH-GTS-21预孵育阻断了β-淀粉样肽诱导的受体激活。低浓度的β-淀粉样肽1-42能够激活L250 T突变体α 7受体。在爪蟾卵母细胞的内源性钙激活的氯离子电流招募受体激活后，因为取代钙与Ba 2+在记录溶液中降低电流幅度。因此，当β-淀粉样肽激活α 7受体时，这些电流至少部分由Ca 2+组成。
The alpha7 nicotinic acetylcholine receptor is highly expressed in hippocampus and in cholinergic projection neurons from the basal forebrain, structures that are particularly vulnerable to the ravages of Alzheimer's disease. Previous work suggests that beta-amyloid peptide can interact with alpha7 nicotinic acetylcholine receptors, although the nature of this interaction has not been well characterized. To test whether beta-amyloid peptide can activate alpha7 nicotinic acetylcholine receptors, we expressed these receptors in Xenopus oocytes and performed two-electrode voltage clamp recordings, characterizing the response to beta-amyloid peptide 1-42 applied at concentrations ranging from I pm to 100 nM. In alpha7-expressing oocytes, beta-amyloid peptide 1-42 elicits inward currents at low concentrations (1-100 pm), whereas at higher concentrations (nM), less effective receptor activation is observed, indicative of receptor desensitization. Preincubation with the alpha7-selective agents, the antagonist methyllycaconatine, and the agonist 4-OH-GTS-21 blocked beta-amyloid peptide-induced receptor activation. beta-amyloid peptide 1-42 at low concentrations was able to activate the L250T mutant alpha7 receptor. The endogenous Ca2+-activated chloride current in Xenopus oocytes is recruited upon receptor activation since replacing Ca2+ with Ba2+ in the recording solution reduced current amplitude. Thus, when beta-amyloid peptide activation of alpha7 receptors occurs, these currents are comprised, at least in part, of Ca2+.