Eva Lasič (Author), Marjeta Lisjak (Author), Anemari Horvat (Author), Mićo Božić (Author), Aleksandra Šakanović (Author), Gregor Anderluh (Author), Alexei Verkhratsky (Author), Nina Vardjan (Author), Jernej Jorgačevski (Author), Matjaž Stenovec (Author), Robert Zorec (Author)

Abstract

Ketamine is an antidepressant with rapid therapeutic onset and long-lasting effect, although the underlying mechanism(s) remain unknown. Using FRET-based nanosensors we found that ketamine increases [cAMP]i in astrocytes. Membrane capacitance recordings, however, reveal fundamentally distinct mechanisms of effects of ketamine and [cAMP]i on vesicular secretion: a rise in [cAMP]i facilitated, whereas ketamine inhibited exocytosis. By directly monitoring cholesterol-rich membrane domains with a fluorescently tagged cholesterol-specific membrane binding domain (D4) of toxin perfringolysin O, we demonstrated that ketamine induced cholesterol redistribution in the plasmalemma in astrocytes, but neither in fibroblasts nor in PC 12 cells. This novel mechanism posits that ketamine affects density and distribution of cholesterol in the astrocytic plasmalemma, consequently modulating a host of processes that may contribute to ketamine's rapid antidepressant action.

Keywords

astrocytes;ketamine;cholesterol;

Data

Language: English
Year of publishing:
Typology: 1.01 - Original Scientific Article
Organization: UL MF - Faculty of Medicine
UDC: 616-092
COBISS: 34434009 Link will open in a new window
ISSN: 2045-2322
Views: 294
Downloads: 74
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Other data

Secondary language: Slovenian
Secondary keywords: astrociti;ketamin;holesterol;
Type (COBISS): Article
Pages: str. 1-12
Issue: ǂVol. ǂ9
Chronology: July 2019
DOI: 10.1038/s41598-019-47459-z
ID: 13181174