Eva Lasič (Avtor),
Marjeta Lisjak (Avtor),
Anemari Horvat (Avtor),
Mićo Božić (Avtor),
Aleksandra Šakanović (Avtor),
Gregor Anderluh (Avtor),
Alexei Verkhratsky (Avtor),
Nina Vardjan (Avtor),
Jernej Jorgačevski (Avtor),
Matjaž Stenovec (Avtor),
Robert Zorec (Avtor)
Povzetek
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.
Ključne besede
astrocytes;ketamine;cholesterol;
Podatki
Jezik: |
Angleški jezik |
Leto izida: |
2019 |
Tipologija: |
1.01 - Izvirni znanstveni članek |
Organizacija: |
UL MF - Medicinska fakulteta |
UDK: |
616-092 |
COBISS: |
34434009
|
ISSN: |
2045-2322 |
Št. ogledov: |
294 |
Št. prenosov: |
74 |
Ocena: |
0 (0 glasov) |
Metapodatki: |
|
Ostali podatki
Sekundarni jezik: |
Slovenski jezik |
Sekundarne ključne besede: |
astrociti;ketamin;holesterol; |
Vrsta dela (COBISS): |
Članek v reviji |
Strani: |
str. 1-12 |
Zvezek: |
ǂVol. ǂ9 |
Čas izdaje: |
July 2019 |
DOI: |
10.1038/s41598-019-47459-z |
ID: |
13181174 |