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首页> 外文期刊>Journal of Neurophysiology >Agonist and toxin sensitivities of ACh-evoked currents on neurons expressing multiple nicotinic ACh receptor subunits.
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Agonist and toxin sensitivities of ACh-evoked currents on neurons expressing multiple nicotinic ACh receptor subunits.

机译：ACh诱发的电流对表达多个烟碱型ACh受体亚基的神经元的激动剂和毒素敏感性。

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1. We have investigated the pharmacological properties of functional nicotinic acetylcholine receptors (nAChRs) on neonatal rat sympathetic neurons from the superior cervical ganglion (SCG) to learn more about the subunit composition of these receptors. These neurons express five nAChR transcripts: alpha 3, alpha 5, alpha 7, beta 2, and beta 4; this finding suggests that SCG neurons may express several different, physiologically distinct, subtypes of nAChRs. 2. To identify potential subtypes, we have characterized currents evoked by different nicotinic agonists and determined their sensitivity to blockade by alpha-bungarotoxin (alpha-BTX) and by neuronal bungarotoxin (n-BTX). From dose-response curves, we find that the ED50 for both cytisine and dimethylphenylpiperazinium (DMPP) is 20 microM and for ACh is 52 microM. n-BTX blocks the ACh-gated currents rapidly, but the kinetics for n-BTX removal is dependent on the duration of the application: brief applications were quickly reversible, whereas prolonged applications took orders of magnitude longer to reverse. 3. Using fast (ms) agonist application, we observed no rapidly desensitizing currents despite the high levels of alpha 7 in these neurons, nor did we observe any currents that could be blocked by alpha-BTX. 4. Using Xenopus oocytes expressing alpha 7 receptors, we show that choline evokes a significant current that is blocked by alpha-BTX. In contrast, choline is much less potent on alpha 3 beta 4 receptors expressed in Xenopus oocytes. Choline can also act as a weak agonist for nAChRs on rat SCG neurons, but its evoked current is not blocked by alpha-BTX. 5. Our results indicate that, when measured at the macroscopic level, most functional nAChRs on SCG neurons behave as a uniform population of receptors, at least with respect to agonist activation and toxin blockade. In comparison with known receptors expressed in heterologous systems, the physiological properties of ACh-evoked currents on SCG neurons are most similar to receptors that have coassembled with both beta 2 and beta 4.
机译：1.我们研究了功能性烟碱型乙酰胆碱受体（nAChRs）对来自上颈神经节（SCG）的新生大鼠交感神经元的药理特性，以了解有关这些受体亚基组成的更多信息。这些神经元表达五个nAChR转录本：α3，α5，α7，β2和β4;α3，α5，α7，β2和β4。这一发现表明，SCG神经元可能表达几种不同的，生理上不同的nAChRs亚型。 2.为了确定潜在的亚型，我们已经对不同烟碱激动剂引起的电流进行了表征，并确定了它们对α-真菌毒素（α-BTX）和神经元Bungarotoxin（n-BTX）阻断的敏感性。从剂量反应曲线中，我们发现，胱氨酸和二甲基苯基哌嗪鎓（DMPP）的ED50为20 microM，ACh为52 microM。 n-BTX迅速阻断了ACh门控电流，但是去除n-BTX的动力学取决于应用的持续时间：短暂的应用可以快速逆转，而长时间的应用则需要更长的数量级才能逆转。 3.使用快速（ms）激动剂应用，尽管这些神经元中的α7含量很高，但我们没有观察到快速的脱敏电流，也没有观察到任何可能被α-BTX阻断的电流。 4.使用表达α7受体的非洲爪蟾卵母细胞，我们显示胆碱可诱发被α-BTX阻断的大量电流。相反，胆碱对非洲爪蟾卵母细胞中表达的α3β4受体的效力要低得多。胆碱还可以充当大鼠SCG神经元上nAChR的弱激动剂，但其诱发的电流不会被α-BTX阻断。 5.我们的结果表明，在宏观水平上，SCG神经元上大多数功能性nAChR的行为均表现为受体的统一，至少在激动剂激活和毒素阻断方面如此。与异源系统中表达的已知受体相比，SCG神经元上ACh诱发的电流的生理特性与与beta 2和beta 4共装配的受体最相似。

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