论文标题
丙泊酚麻醉期间膜纳米域稳态随剂量和温度的作用
Membrane Nanodomains Homeostasis During Propofol Anesthesia as Function of Dosage and Temperature
论文作者
论文摘要
某些麻醉剂结合并增强γ-氨基丁基型受体，但尚无通用大麻醉的通用机制。此外，不了解经常遇到的并发症，例如麻醉诱发的失忆症。一般麻醉药是疏水分子很容易溶于脂质双层。最近，结果表明，从固定细胞提取的囊泡中的一般麻醉剂均匀相分离。不清楚的是，在生理条件下，一般麻醉剂是否会诱导脂质双层的扰动，以及这是否有助于意识的短暂丧失或麻醉副作用。在这里，我们表明丙泊酚渗透脂质纳米域中的质膜外部和内部小叶中完整的细胞中的脂质纳米域，以浓度依赖于膜的纳米域影响：1μM至5μm丙泊酚Dembofol Dembofol Dembofol Demant稳定稳定纳米域；但是，丙泊酚浓度高于5μm，随着时间的推移稳定纳米域。稳定仅发生在生理温度和完整细胞中。此过程需要ARP2/3介导的肌动蛋白成核和肌球蛋白II活性。 GABA受体活性增强了纳米域稳定的速率。我们的结果表明，主动纳米域稳态抵消了最初的破坏，导致皮质肌动蛋白发生巨大变化。
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 μM to 5 μM propofol destabilize nanodomains; however, propofol concentrations higher than 5 μM 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.
