scholarly journals Stabilizing membrane domains antagonizes n-alcohol anesthesia

2016 ◽  
Author(s):  
B.B. Machta ◽  
E. Grey ◽  
M. Nouri ◽  
N.L.C. McCarthy ◽  
E.M. Gray ◽  
...  

AbstractDiverse molecules induce general anesthesia with potency strongly correlated both with their hydrophobicity and their effects on certain ion channels. We recently observed that several n-alcohol anesthetics inhibit heterogeneity in plasma membrane derived vesicles by lowering the critical temperature (Tc) for phase separation. Here we exploit conditions that stabilize membrane heterogeneity to further test the correlation between the anesthetic potency of n-alcohols and effects on Tc. First we show that hexadecanol acts oppositely to n-alcohol anesthetics on membrane mixing and antagonizes ethanol induced anesthesia in a tadpole behavioral assay. Second, we show that two previously described ‘intoxication reversers’ raise Tc and counter ethanol’s effects in vesicles, mimicking the findings of previous electrophysiological and behavioral measurements. Third, we find that hydrostatic pressure, long known to reverse anesthesia, also raises Tc in vesicles with a magnitude that counters the effect of butanol at relevant concentrations and pressures. Taken together,these results demonstrate that ΔTc predicts anesthetic potency for n-alcohols better than hydrophobicity in a range of contexts, supporting a mechanistic role for membrane heterogeneity in general anesthesia.

2020 ◽  
Author(s):  
Tetsuo Mioka ◽  
Guo Tian ◽  
Wang Shiyao ◽  
Takuma Tsuji ◽  
Takuma Kishimoto ◽  
...  

AbstractMembrane phase separation accompanied with micron-scale domains of lipids and proteins occurs in artificial membranes; however, a similar large phase separation has not been reported in the plasma membrane of the living cells. We demonstrate here that a stable micron-scale protein-free region is generated in the plasma membrane of the yeast mutants lacking phosphatidylserine. We named this region the “void zone”. Transmembrane proteins, peripheral membrane proteins, and certain phospholipids are excluded from the void zone. The void zone is rich in ergosterol and requires ergosterol and sphingolipids for its formation. These characteristics of the void zone are similar to the properties of the cholesterol-enriched domain in phase-separated artificial membranes. We propose that phosphatidylserine prevents the formation of the void zone by preferentially interacting with ergosterol. We also found that void zones were frequently in contact with vacuoles, in which a membrane domain was also formed at the contact site.Summary statementYeast cells lacking phosphatidylserine generate protein-free plasma membrane domains, and vacuoles contact with this domain. This is the first report of micron-scale plasma membrane domains in living cells.


2015 ◽  
Vol 57 ◽  
pp. 109-119 ◽  
Author(s):  
Senthil Arumugam ◽  
Patricia Bassereau

The understanding of lipid membranes and their organization has undergone significant development with better techniques and therefore more resolved experiments. Many new factors and organizing principles have been discovered, and interplay between these factors is expected to result in rich functional behaviours. The major factors regulating the lateral membrane heterogeneity, apart from the well-studied phase separation, are cytoskeleton pinning, clustering of lipids and curvature. These factors are effective means to create membrane domains that provide rich biological functionality. We review the recent advances and concepts of membrane heterogeneity organization by curvature, cytoskeleton and clustering proteins.


Author(s):  
J.M. Robinson ◽  
J.M Oliver

Specialized regions of plasma membranes displaying lateral heterogeneity are the focus of this Symposium. Specialized membrane domains are known for certain cell types such as differentiated epithelial cells where lateral heterogeneity in lipids and proteins exists between the apical and basolateral portions of the plasma membrane. Lateral heterogeneity and the presence of microdomains in membranes that are uniform in appearance have been more difficult to establish. Nonetheless a number of studies have provided evidence for membrane microdomains and indicated a functional importance for these structures.This symposium will focus on the use of various imaging modalities and related approaches to define membrane microdomains in a number of cell types. The importance of existing as well as emerging imaging technologies for use in the elucidation of membrane microdomains will be highlighted. The organization of membrane microdomains in terms of dimensions and spatial distribution is of considerable interest and will be addressed in this Symposium.


2002 ◽  
Vol 277 (33) ◽  
pp. 30325-30336
Author(s):  
Daniel Wüstner ◽  
Andreas Herrmann ◽  
Mingming Hao ◽  
Frederick R. Maxfield

2005 ◽  
Vol 72 (1) ◽  
Author(s):  
D. Lampakis ◽  
D. Palles ◽  
E. Liarokapis ◽  
S. M. Kazakov ◽  
J. Karpinski

1990 ◽  
Vol 69 (6) ◽  
pp. 2239-2247 ◽  
Author(s):  
D. M. Pickles ◽  
D. Ogston ◽  
A. G. Macdonald

A novel cuvette was used to subject citrated platelet-rich plasma (PRP) to high hydrostatic pressure with negligible contamination by He (used for compression of the apparatus). Aggregation was induced at pressure by ADP and quantified turbidimetrically. The maximum degree of aggregation (MDA) was reduced from a control level of 82.2 to 53.6% by exposure to 101 ATA. Because decompression bubbles did not form, aggregation was also measured immediately after a compression cycle. After exposure to 101 ATA hydrostatic pressure, platelets responded normally to ADP at 1 ATA. In a matching apparatus, PRP was equilibrated with high partial pressures of inert gases. Normal physiological plasma Po2 and pH were maintained during equilibration. N2O (5 ATA) reduced the MDA from 86.5 (control) to 58.1%. N2 (51 ATA) reduced the MDA from 74.7 (control) to 51.6%, and 101 ATA Pn2 reduced the MDA from 78.0 (control) to 32.3%. He (100 ATA) reduced the MDA from 83.6 to 38.6%. It was concluded that platelet aggregation was relatively sensitive to hydrostatic pressure and less sensitive to inert gases than predicted from their anesthetic potency ratios.


Genus ◽  
2021 ◽  
Vol 77 (1) ◽  
Author(s):  
Andrea Priulla ◽  
Nicoletta D’Angelo ◽  
Massimo Attanasio

AbstractThis paper investigates gender differences in university performances in Science, Technology, Engineering and Mathematics (STEM) courses in Italy, proposing a novel application through the segmented regression models. The analysis concerns freshmen students enrolled at a 3-year STEM degree in Italian universities in the last decade, with a focus on the relationship between the number of university credits earned during the first year (a good predictor of the regularity of the career) and the probability of getting the bachelor degree within 4 years. Data is provided by the Italian Ministry of University and Research (MIUR). Our analysis confirms that first-year performance is strongly correlated to obtaining a degree within 4 years. Furthermore, our findings show that gender differences vary among STEM courses, in accordance with the care-oriented and technical-oriented dichotomy. Males outperform females in mathematics, physics, chemistry and computer science, while females are slightly better than males in biology. In engineering, female performance seems to follow the male stream. Finally, accounting for other important covariates regarding students, we point out the importance of high school background and students’ demographic characteristics.


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