Effects of propofol on recombinant AMPA receptor channels
Effects of propofol on recombinant AMPA receptor channels
复制标题
DOI：
10.1016/j.ejphar.2005.02.012
复制
发表时间：
2005-03-21
影响因子：
5
通讯作者：
Bufler, J
中科院分区：
文献类型：
--
作者：
Krampfl, K;Cordes, AL;Bufler, J
使用快速激动剂应用技术通过膜片钳研究研究了麻醉剂异丙酚与重组人 AMPA 型谷氨酸受体通道的相互作用。尽管异丙酚对抑制性突触传递和电压门控钠通道具有显着影响，但也有证据表明对 AMPA 受体具有特定的药理作用。在我们的研究中，我们观察到长期存在谷氨酸和异丙酚时 AMPA 受体通道脱敏减慢，这可能是先前研究中观察到的通过 AMPA 受体通道的离子电流增强的原因。虽然谷氨酸受体 1、谷氨酸受体 2 和谷氨酸受体 3 AMPA 受体的脱敏率和程度有所增加，但没有观察到电流上升时间、峰值电流幅度和失活特性的影响。因此，我们的研究结果表明与控制 AMPA 受体通道脱敏的过程存在孤立的相互作用，而不是表明由于激动剂结合和解除结合而与通道打开和关闭过程相互作用。所描述的药理作用部分类似于已知与通道脱敏相互作用的环噻嗪和阿尼西坦等化合物的药理作用。 (c) 2005 Elsevier B.V. 保留所有权利。
The interaction of the anaesthetic propofol with recombinant human AMPA-type glutamate receptor channels was investigated by a patch-clamp study using fast agonist application techniques. Despite the marked effects of propofol on inhibitory synaptic transmission and voltage gated sodium channels, there is also evidence for a specific pharmacological action on AMPA receptors. In our study, we observed a deceleration of AMPA receptor channel desensitization in the prolonged presence of glutamate and propofol that is likely to account for the enhancement of ion currents through AMPA receptor channels observed in previous studies. While there was an increase in the rate and extent of desensitization at glutamate receptor 1, glutamate receptor 2, and glutamate receptor 3 AMPA receptors, no affection of current rise time, peak current amplitude, and deactivation properties was observed. Thus, our findings point to an isolated interaction with processes that control desensitization of AMPA receptor channels rather than indicating an interaction with channel opening and closing processes due to agonist binding and unbinding. The pharmacological effect described resembles in part that of compounds like cyclothiazide and aniracetam which are known to interact with channel desensitization. (c) 2005 Elsevier B.V. All rights reserved.