Pressure-induced exclusion of a local anesthetic from model and nerve membranes.
Pressure-induced exclusion of a local anesthetic from model and nerve membranes.
复制标题
压力诱导将局部麻醉剂从模型和神经膜中排除。
作者：
M. Auger;H. Jarrell;I. Smith;P. Wong;D. Siminovitch;H. Mantsch
由于麻醉状态可以通过压力逆转这一事实已经得到了充分的证实，因此许多关于局麻药和全身麻药作用机制的分子理论都可以通过改变压力来检验。利用傅里叶变换红外光谱，我们在这里报告了第一次直接观察到局部麻醉剂丁卡因在压力下从脂质双分子层排出。此外，我们首次证实这种现象在模型膜以及有髓鞘和无髓鞘神经膜中都是常见的，证明了模型膜系统的实用性。在模型系统中，这种行为的一个显著特征是，在高pH值的饱和磷脂酰胆碱中，只有在胆固醇存在的情况下才会发生排出，其对酰基链的排序效应显然有助于压力将麻醉剂挤出双分子层。这种压力诱导的现象可能为了解压力对麻醉的拮抗作用的分子机制提供了新的思路。
Because it is well established that the anesthetic state can be reversed by pressure, a number of molecular theories that have been proposed for the mechanism of action of both local and general anesthetics can be tested by varying the pressure. Using Fourier transform infrared spectroscopy, we report here the first direct observation of the expulsion from lipid bilayers of a local anesthetic, tetracaine, by pressure. Moreover, we establish for the first time that this phenomenon is common to both model membranes and to myelinated and unmyelinated nerve membranes, vindicating the utility of model membrane systems. A distinctive feature of this behavior in model systems is that, in saturated phosphatidylcholines at high pH, expulsion only occurs in the presence of cholesterol, whose ordering effect on the acyl chains evidently assists pressure in squeezing the anesthetic out of the bilayer. This pressure-induced phenomenon may provide insight into the molecular mechanisms underlying the antagonistic effect of pressure against anesthesia.