Membrane nanodomains homeostasis during propofol anesthesia as function of dosage and temperature.
Membrane nanodomains homeostasis during propofol anesthesia as function of dosage and temperature.
复制标题
异丙酚麻醉期间膜纳米域稳态随剂量和温度的变化。
DOI：
10.1016/j.bbamem.2020.183511
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Pralle,Arnd
中科院分区：
文献类型：
--
作者：
Jin,Weixiang;Zucker,Michael;Pralle,Arnd
一些麻醉药结合并增强γ -氨基丁酸型受体，但对全身麻醉的普遍机制尚不清楚。此外，经常遇到的并发症，如麻醉引起的健忘症是不了解。全麻是疏水分子，容易溶解到脂质双分子层中。最近有研究表明，全身麻醉药会干扰固定细胞中提取的囊泡的相分离。目前尚不清楚在生理条件下全麻是否会引起脂质双分子层的扰动，以及这是否会导致短暂的意识丧失或麻醉副作用。在这里，我们发现异丙酚扰乱了完整细胞中细胞膜内外小叶的脂质纳米结构域，并以浓度依赖的方式影响膜纳米结构域：1 {\mu}M至5 {\mu}M异丙酚破坏纳米结构域的稳定；然而，当异丙酚浓度大于5 {\mu}M时，随着时间的推移，纳米结构域趋于稳定。稳定只发生在生理温度和完整的细胞。这一过程需要ARP2/3介导的肌动蛋白成核和Myosin II活性。GABA受体的活性增强了纳米结构域稳定的速率。我们的研究结果表明，活跃的纳米结构域稳态抵消了引起皮质肌动蛋白大变化的初始破坏。
Some anesthetics bind and potentiate gamma-aminobutyric-acid-type receptors, but no universal mechanism for general anesthesia is known. Furthermore, often encountered complications such as anesthesia induced amnesia are not understood. General anesthetics are hydrophobic molecules easily dissolving into lipid bilayers. Recently, it was shown that general anesthetics perturb phase separation in vesicles extracted from fixed cells. Unclear is whether under physiological conditions general anesthetics induce perturbation of the lipid bilayer, and whether this contributes to the transient loss of consciousness or anesthesia side effects. Here we show that propofol perturbs lipid nanodomains in the outer and inner leaflet of the plasma membrane in intact cells, affecting membrane nanodomains in a concentration dependent manner: 1 {\mu}M to 5 {\mu}M propofol destabilize nanodomains; however, propofol concentrations higher than 5 {\mu}M stabilize nanodomains with time. Stabilization occurs only at physiological temperature and in intact cells. This process requires ARP2/3 mediated actin nucleation and Myosin II activity. The rate of nanodomain stabilization is potentiated by GABA receptor activity. Our results show that active nanodomain homeostasis counteracts the initial disruption causing large changes in cortical actin.