Matjaž Stenovec (Avtor), Baoman Li (Avtor), Alexei Verkhratsky (Avtor), Robert Zorec (Avtor)

Povzetek

Ketamine, a general anaesthetic and psychotomimetic drug, exerts rapid, potent and long-lasting antidepressant effect, albeit the cellular and molecular mechanisms of this action are yet to be discovered. Besides targeting neuronal NMDARs fundamental for synaptic transmission, ketamine affects the function of astroglia the key homeostatic cells of the central nervous system that contribute to pathophysiology of psychiatric diseases including depression. Here we review studies revealing that (sub)anaesthetic doses of ketamine elevate intracellular cAMP concentration ([cAMP]i) in astrocytes, attenuate stimulus-evoked astrocyte calcium signalling, which regulates exocytotic secretion of gliosignalling molecules, and stabilize the vesicle fusion pore in a narrow configuration possibly hindering cargo discharge or vesicle recycling. Next we discuss how ketamine affects astroglial capacity to control extracellular K+ by reducing cytoplasmic mobility of vesicles delivering the inward rectifying potassium channel (Kir4.1) to the plasmalemma. Modified astroglial K+ buffering impacts upon neuronal excitability as demonstrated in the lateral habenula rat model of depression. Finally, we highlight the recent discovery that ketamine rapidly redistributes cholesterol in the plasmalemma of astrocytes, but not in fibroblasts nor in neuronal cells. This alteration of membrane structure may modulate a host of processes that synergistically contribute to ketamine's rapid and prominent antidepressant action.

Ključne besede

astroglia;ketamine;exocytosis;

Podatki

Jezik: Angleški jezik
Leto izida:
Tipologija: 1.02 - Pregledni znanstveni članek
Organizacija: UL MF - Medicinska fakulteta
UDK: 616-092
COBISS: 17655811 Povezava se bo odprla v novem oknu
ISSN: 1873-7064
Št. ogledov: 76
Št. prenosov: 35
Ocena: 0 (0 glasov)
Metapodatki: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

Ostali podatki

Sekundarni jezik: Slovenski jezik
Sekundarne ključne besede: astroglia;ketamin;eksocitoza;
Vrsta dela (COBISS): Članek v reviji
Strani: str. 1-14
Zvezek: ǂVol. ǂ173
Čas izdaje: Aug. 2020
DOI: 10.1016/j.neuropharm.2020.108158
ID: 15795557