Kinetics of nicotinic acetylcholine ion channels in the presence of intravenous anaesthetics and induction agents
Kinetics of nicotinic acetylcholine ion channels in the presence of intravenous anaesthetics and induction agents
复制标题
静脉麻醉剂和诱导剂存在下烟碱乙酰胆碱离子通道的动力学
DOI：
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发表时间：
1992
影响因子：
7.3
通讯作者：
E. Wegrzynowicz
中科院分区：
文献类型：
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作者：
R. Wachtel;E. Wegrzynowicz
用250 nm乙酰胆碱激活的单通道电流记录了BC3H1小鼠肿瘤细胞贴壁的细胞电流。分别记录在不使用和存在阿霉素、地西泮、依托咪酯、芬太尼、氯胺酮、哌嗪或异丙酚时的通道。所有麻醉药均缩短了通道打开时间，但未改变单通道电流振幅。可使开放时间分布时间常数降低50%的药物浓度为：99 μm α xalone、66 μm地西泮、57 μm依托咪酯、26 μm芬太尼、15 μm氯胺酮、16 μm哌啶或81 μm异丙酚。氯胺酮、哌嗪和异丙酚的浓度与治疗使用这些药物时达到的血浆水平相当时，可减少通道打开时间，而阿哌龙、地西泮、依托咪酯和芬太尼只有在高于临床水平时才会减少通道打开时间。这些药物在减少通道打开时间时的效力似乎与它们的辛醇/缓冲分配系数直接相关。然而，与预期相反，具有较高分割系数的药物在改变通道开放时间方面的作用较小。氯胺酮和哌替啶在封闭时间分布中产生了突出的第三个分量，否则可以用两个指数分量的和来很好地描述。Alphaxalone， diazepam和依托咪酯也产生了少量的第三种成分，而异丙酚或芬太尼中没有发现额外的成分。这些额外的组件可能来自于通道的额外封闭状态的创建。我们得出的结论是，这些药物不仅仅是通过脂质双分子层施加非特异性作用来改变通道性质，而且它们可能不是都通过类似的机制起作用。
1 Single channel currents activated by 250 nm acetylcholine were recorded from cell‐attached patches of BC3H1 mouse tumour cells grown in culture. Channels were recorded in the absence and presence of alphaxalone, diazepam, etomidate, fentanyl, ketamine, meperidine, or propofol. 2 All of the anaesthetics tested shortened channel open time but did not alter single channel current amplitude. Drug concentrations calculated to reduce the time constant of open‐time distributions by 50% were 99 μm alphaxalone, 66 μm diazepam, 57 μm etomidate, 26 μm fentanyl, 15 μm ketamine, 16 μm meperidine, or 81 μm propofol. 3 Ketamine, meperidine, and propofol reduced channel open time at concentrations comparable to plasma levels attained during therapeutic use of these agents, while alphaxalone, diazepam, etomidate, and fentanyl reduced channel open time only at levels higher than those encountered clinically. 4 The potency of these drugs in decreasing channel open time appears to be directly correlated with their octanol/buffer partition coefficients. In contrast to expectations, however, agents with higher partition coefficients were less potent in altering channel open time. 5 Ketamine and meperidine produced a prominent third component in closed‐time distributions, which were otherwise well described by the sum of two exponential components. Alphaxalone, diazepam, and etomidate also produced a small third component, while no additional component was seen with propofol or fentanyl. These additional components probably arise from creation of an additional closed state of the channel. 6 We conclude that these agents are not altering channel properties merely by exerting non‐specific effects via the lipid bilayer and that they are probably not all acting by similar mechanisms.
烟碱乙酰胆碱受体的激活。
影响因子：
3.4
作者：
Sine,SM;Steinbach,JH
通讯作者：
Steinbach,JH
影响因子：
3.4
作者：
SIGWORTH, FJ;SINE, SM
通讯作者：
SINE, SM