1. Membrane Nanodomains Homeostasis During Propofol Anesthesia as Function of Dosage and Temperature
- Author
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Jin, Weixiang, Zucker, Michael, and Pralle, Arnd
- Subjects
Quantitative Biology - Cell Behavior ,Quantitative Biology - Neurons and Cognition - Abstract
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.
- Published
- 2020
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