Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Studies on the mechanism of membrane mediated general anesthesia

Mahmud Arif Pavel, E. Nicholas Petersen, Hao Wang, Richard A. Lerner, Scott B. Hansen
doi: https://doi.org/10.1101/313973
Mahmud Arif Pavel
1Department of Molecular Medicine, The Scripps Research Institute, Jupiter, Florida 33458, USA
2Department of Neuroscience, The Scripps Research Institute, Jupiter, Florida 33458, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
E. Nicholas Petersen
1Department of Molecular Medicine, The Scripps Research Institute, Jupiter, Florida 33458, USA
2Department of Neuroscience, The Scripps Research Institute, Jupiter, Florida 33458, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hao Wang
1Department of Molecular Medicine, The Scripps Research Institute, Jupiter, Florida 33458, USA
2Department of Neuroscience, The Scripps Research Institute, Jupiter, Florida 33458, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Richard A. Lerner
3Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Scott B. Hansen
1Department of Molecular Medicine, The Scripps Research Institute, Jupiter, Florida 33458, USA
2Department of Neuroscience, The Scripps Research Institute, Jupiter, Florida 33458, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: shansen@scripps.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

ABSTRACT

Inhaled anesthetics are a chemically diverse collection of hydrophobic molecules that robustly activate TWIK related K+ channels (TREK-1) and reversibly induce loss of consciousness. For a hundred years anesthetics were speculated to target cellular membranes, yet no plausible mechanism emerged to explain a membrane effect on ion channels. Here we show that inhaled anesthetics (chloroform and isoflurane) activate TREK-1 through disruption of palmitate-mediated localization of phospholipase D2 (PLD2) to lipid rafts and subsequent production of signaling lipid phosphatidic acid (PA). Catalytically dead PLD2 robustly blocks anesthetic TREK-1 currents in cell patch-clamp. Localization of PLD2 renders the anesthetic-insensitive TRAAK channel sensitive. General anesthetics chloroform, isoflurane, diethyl ether, xenon, and propofol disrupt lipid rafts and activate PLD2. In the whole brain of flies, anesthesia disrupts rafts and PLDnull flies resist anesthesia. Our results establish a membrane mediated target of inhaled anesthesia and suggest PA helps set anesthetic sensitivity in vivo.

Footnotes

  • Anesthetic disruption of lipid raft is now shown in the whole brain of a fly. Phospholipase D (PLD) null flies resist anesthesia. Chloroform and isoflurane dose-response curves for PLD/raft disruption are added. And the non-immobilizer F6 was tested for PLD activation.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted June 19, 2019.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Studies on the mechanism of membrane mediated general anesthesia
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Studies on the mechanism of membrane mediated general anesthesia
Mahmud Arif Pavel, E. Nicholas Petersen, Hao Wang, Richard A. Lerner, Scott B. Hansen
bioRxiv 313973; doi: https://doi.org/10.1101/313973
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Studies on the mechanism of membrane mediated general anesthesia
Mahmud Arif Pavel, E. Nicholas Petersen, Hao Wang, Richard A. Lerner, Scott B. Hansen
bioRxiv 313973; doi: https://doi.org/10.1101/313973

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Neuroscience
Subject Areas
All Articles
  • Animal Behavior and Cognition (4658)
  • Biochemistry (10313)
  • Bioengineering (7636)
  • Bioinformatics (26240)
  • Biophysics (13481)
  • Cancer Biology (10648)
  • Cell Biology (15360)
  • Clinical Trials (138)
  • Developmental Biology (8463)
  • Ecology (12776)
  • Epidemiology (2067)
  • Evolutionary Biology (16794)
  • Genetics (11372)
  • Genomics (15430)
  • Immunology (10580)
  • Microbiology (25087)
  • Molecular Biology (10172)
  • Neuroscience (54233)
  • Paleontology (398)
  • Pathology (1660)
  • Pharmacology and Toxicology (2883)
  • Physiology (4326)
  • Plant Biology (9213)
  • Scientific Communication and Education (1582)
  • Synthetic Biology (2544)
  • Systems Biology (6761)
  • Zoology (1458)