液体全身麻醉剂降低质膜囊泡中的临界温度。
Liquid general anesthetics lower critical temperatures in plasma membrane vesicles.
机构信息
Department of Biophysics, University of Michigan, Ann Arbor MI 48109.
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton NJ 08544.
出版信息
Biophys J. 2013 Dec 17;105(12):2751-9. doi: 10.1016/j.bpj.2013.11.005.
A large and diverse array of small hydrophobic molecules induce general anesthesia. Their efficacy as anesthetics has been shown to correlate both with their affinity for a hydrophobic environment and with their potency in inhibiting certain ligand-gated ion channels. In this study we explore the effects that n-alcohols and other liquid anesthetics have on the two-dimensional miscibility critical point observed in cell-derived giant plasma membrane vesicles (GPMVs). We show that anesthetics depress the critical temperature (Tc) of these GPMVs without strongly altering the ratio of the two liquid phases found below Tc. The magnitude of this affect is consistent across n-alcohols when their concentration is rescaled by the median anesthetic concentration (AC50) for tadpole anesthesia, but not when plotted against the overall concentration in solution. At AC50 we see a 4°C downward shift in Tc, much larger than is typically seen in the main chain transition at these anesthetic concentrations. GPMV miscibility critical temperatures are also lowered to a similar extent by propofol, phenylethanol, and isopropanol when added at anesthetic concentrations, but not by tetradecanol or 2,6 diterbutylphenol, two structural analogs of general anesthetics that are hydrophobic but have no anesthetic potency. We propose that liquid general anesthetics provide an experimental tool for lowering critical temperatures in plasma membranes of intact cells, which we predict will reduce lipid-mediated heterogeneity in a way that is complimentary to increasing or decreasing cholesterol. Also, several possible implications of our results are discussed in the context of current models of anesthetic action on ligand-gated ion channels.
大量不同种类的疏水分子可诱导全身麻醉。它们作为麻醉剂的功效与其对疏水环境的亲和力及其抑制某些配体门控离子通道的效力相关。在这项研究中,我们探讨了 n-醇和其他液体麻醉剂对在细胞衍生的巨质膜囊泡(GPMV)中观察到的二维混溶性临界点的影响。我们发现麻醉剂会降低这些 GPMV 的临界温度(Tc),而不会强烈改变 Tc 以下发现的两个液相的比例。当用 tadpole 麻醉的中位数麻醉浓度(AC50)对 n-醇的浓度进行缩放时,这种影响在 n-醇之间的幅度是一致的,但当根据溶液中的总浓度绘制时则不然。在 AC50 时,我们看到 Tc 向下移动 4°C,这比在这些麻醉浓度下通常在主链转变中看到的要大得多。当以麻醉浓度添加普洛福、苯乙醇和异丙醇时,GPMV 混溶性临界温度也会降低到类似程度,但十四烷醇或 2,6 二叔丁基苯酚则不会,这两种一般麻醉剂的结构类似物是疏水性的,但没有麻醉效力。我们提出,液体全身麻醉剂为降低完整细胞质膜的临界温度提供了一种实验工具,我们预测这将以与增加或减少胆固醇互补的方式降低脂质介导的异质性。此外,还在配体门控离子通道麻醉作用的当前模型背景下讨论了我们研究结果的几个可能的含义。