Matsuura Takayuki, Kamiya Yoshinori, Itoh Hideki, Higashi Tomoko, Yamada Yoshitsugu, Andoh Tomio
Department of Anaesthesiology, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
Anesthesiology. 2002 Dec;97(6):1541-9. doi: 10.1097/00000542-200212000-00029.
Neuronal nicotinic acetylcholine receptors (nAchRs) are inhibited by low concentrations of volatile anesthetics. However, it is not clear whether this phenomenon contributes to the anesthetic effects of volatile anesthetics. Effects of a volatile anesthetic (isoflurane) and structurally related nonimmobilizers (F6: 1,2-dichlorohexafluorocyclobutane, F8: 2,3-dichlorooctafluorobutane) on the current mediated through neuronal nAchRs were studied.
This study investigated neuronal nAchRs in PC12 cells and acutely dissociated rat medial habenula (MHb) neurons. Whole cell currents elicited by 30 microm nicotine were recorded in the absence and presence of the halogenated agents. The minimum alveolar concentrations (MACs) for F6 and F8 were predicted from Meyer-Overton correlation.
All halogenated compounds inhibited the nicotine-induced current in a concentration-dependent manner in PC12 cells. In MHb neurons, while isoflurane and F6 significantly inhibited the nicotine-induced peak current, F8 failed to inhibit it. The peak currents in the presence of isoflurane at 1.7 MAC, of F6 at 2.4 MAC, and of F8 at 2.2 MAC were 12, 31, and 97% of control, respectively.
Isoflurane, F6, and F8 inhibited ganglion-type nAchRs in PC12 cells independent from their abilities to produce the anesthetic state. In MHb neurons, isoflurane and F6, which lack the immobilizing effect but has the amnesic effect, inhibited nAchRs. Native brain nicotinic receptors in MHb neurons were almost insensitive to F8, which lacks both the immobilizing and the amnesic effect. These results are consistent with the hypothesis that inhibition of nAchRs in MHb neurons is not important for the anesthetic effect but may contribute to the amnesic effect of these agents.
低浓度挥发性麻醉药可抑制神经元烟碱型乙酰胆碱受体（nAchRs）。然而，尚不清楚该现象是否对挥发性麻醉药的麻醉作用有影响。本研究探讨了挥发性麻醉药（异氟烷）及结构相关的非麻醉剂（F6：1,2 - 二氯六氟环丁烷，F8：2,3 - 二氯八氟丁烷）对通过神经元nAchRs介导的电流的影响。
本研究在PC12细胞和急性分离的大鼠内侧缰核（MHb）神经元中研究神经元nAchRs。在存在和不存在卤化剂的情况下，记录由30微摩尔尼古丁引发的全细胞电流。根据迈耶 - 奥弗顿相关性预测F6和F8的最低肺泡浓度（MACs）。
所有卤化化合物在PC12细胞中均以浓度依赖性方式抑制尼古丁诱导的电流。在MHb神经元中，异氟烷和F6显著抑制尼古丁诱导的峰值电流，而F8未能抑制。在1.7MAC的异氟烷、2.4MAC的F6和2.2MAC的F8存在下，峰值电流分别为对照的12%、31%和97%。
异氟烷、F6和F8在PC12细胞中抑制神经节型nAchRs，与其产生麻醉状态的能力无关。在MHb神经元中，缺乏麻醉作用但具有遗忘作用的异氟烷和F6抑制nAchRs。MHb神经元中的天然脑烟碱受体对缺乏麻醉和遗忘作用的F8几乎不敏感。这些结果与以下假设一致，即抑制MHb神经元中的nAchRs对麻醉作用不重要，但可能有助于这些药物的遗忘作用。
