About: Studies on the mechanism of general anesthesia

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An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Studies on the mechanism of general anesthesia
Creator	Wang, Hao Petersen, E Hansen, Scott Lerner, Richard Pavel, Mahmud
source	Medline; PMC
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 100 y, 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 phospholipase D2 (PLD2) localization to lipid rafts and subsequent production of signaling lipid phosphatidic acid (PA). Catalytically dead PLD2 robustly blocks anesthetic TREK-1 currents in whole-cell patch-clamp recordings. Localization of PLD2 renders the TRAAK channel sensitive, a channel that is otherwise anesthetic insensitive. General anesthetics, such as chloroform, isoflurane, diethyl ether, xenon, and propofol, disrupt lipid rafts and activate PLD2. In the whole brain of flies, anesthesia disrupts rafts and PLD(null) flies resist anesthesia. Our results establish a membrane-mediated target of inhaled anesthesia and suggest PA helps set thresholds of anesthetic sensitivity in vivo.
has issue date	2020-06-16(xsd:dateTime)
bibo:doi	10.1073/pnas.2004259117
bibo:pmid	32467161
has license	cc-by-nc-nd
sha1sum (hex)	614db1e763444be2bedd03d84634f4aea0a65060
schema:url	https://doi.org/10.1073/pnas.2004259117
resource representing a document's title	Studies on the mechanism of general anesthesia
has PubMed Central identifier	PMC7306821
has PubMed identifier	32467161
schema:publication	Proc Natl Acad Sci U S A
resource representing a document's body	covid:614db1e763444be2bedd03d84634f4aea0a65060#body_text
is schema:about of	named entity 'brain' named entity 'Localization' named entity 'flies' named entity 'anesthetic' named entity 'TREK-1' »more»

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