The neuronal nicotinic α4β2 receptor has a high maximal probability of being open
The neuronal nicotinic α4β2 receptor has a high maximal probability of being open
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DOI：
10.1111/j.1476-5381.2010.00761.x
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发表时间：
2010-08-01
影响因子：
7.3
通讯作者：
Steinbach, Joe H.
中科院分区：
文献类型：
--
作者：
Li, Ping;Steinbach, Joe H.
背景和目的：离子通道的一个基本性质是当被一个浓度的激动剂刺激时，通道将被打开的概率（P（打开）），该浓度的激动剂引起最大反应。该值对于解释通道激活方面的稳态浓度-响应关系以及理解增强响应的药物的作用至关重要。我们使用非平稳噪声分析来估计烟碱α 4 β 2受体开放的最大概率。实验方法：使用全细胞电压钳研究稳定转染表达人α 4 β 2烟碱受体的HEK 293细胞。应用烟碱类激动剂（乙酰胆碱、烟碱、野靛碱和5-碘A-85380），分析了全细胞电流的方差与平均电流的关系。对于乙酰胆碱和尼古丁，方差和平均值之间的关系表明，最大P（开放）大于0.8。激动剂可激活通道的数量估计为每个细胞约1000个。当乙酰胆碱（18 pS），尼古丁（17 pS）或5-碘A-85380（17 pS）引起电流时，在-60 mV的平均单通道电导是不可区分的，而野靛碱的值更大（24 pS）。结论和影响：神经元烟碱α 4 β 2受体具有最大的开放概率大于0.8。这一结论适用于含有三个α 4和两个β 2亚基的受体（低灵敏度化学计量），但可能不适用于含有两个α 4和三个β 2亚基的受体（高灵敏度化学计量）。1903年-1905年，这个问题。要查看此评论，请访问http://dx.doi.org/10.1111/j.1476-5381.2010.00868.x。
Background and purpose:A fundamental property of transmitter-gated ion channels is the probability a channel will be open (P(open)) when stimulated by a concentration of agonist that elicits a maximal response. This value is critical for interpreting steady-state concentration-response relationships in terms of channel activation, and for understanding the actions of drugs that potentiate responses. We used analysis of non-stationary noise to estimate the maximal probability the nicotinic alpha 4 beta 2 receptor is open.Experimental approach:HEK293 cells stably transfected to express human alpha 4 beta 2 nicotinic receptors were studied using whole-cell voltage clamp. Nicotinic agonists (acetylcholine, nicotine, cytisine and 5-iodo A-85380) were applied, and the relationship between variance of the elicited whole-cell current and mean current was analysed.Key results:The variance did not increase linearly with the mean current. For acetylcholine and nicotine the relationship between variance and mean indicates that the maximal P(open) is greater than 0.8. The number of agonist-activatable channels was estimated to be about 1000 per cell. The mean single channel conductance at -60 mV was indistinguishable when currents were elicited by acetylcholine (18 pS), nicotine (17 pS) or 5-iodo A-85380 (17 pS), whereas the value for cytisine was larger (24 pS).Conclusions and implications:The neuronal nicotinic alpha 4 beta 2 receptor has a maximal probability of being open that is greater than 0.8. This conclusion applies to the receptor containing three alpha 4 and two beta 2 subunits (the low-sensitivity stoichiometry), but may not apply to the receptor containing two alpha 4 and three beta 2 subunits (the high-sensitivity stoichiometry).This article is commented on by Papke, pp. 1903-1905 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2010.00868.x.