Studies on the mechanism of general anesthesia.

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 anesthet

SUBMITTER: Pavel MA 

PROVIDER: S-EPMC7306821 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature