20.500.12556/RUL-137800 Astrocytes in rapid ketamine antidepressant action 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. astroglia ketamine exocytosis cytosolic excitability potassium homeostasis cholesterol astroglia ketamin eksocitoza true false true Angleški jezik Slovenski jezik Članek v reviji 2022-07-01 08:40:28 2022-07-01 08:40:33 2022-09-15 04:15:49 0000-00-00 00:00:00 2020 0 0 14 str. Vol. 173, art. 108158 Aug. 2020 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616-092 1873-7064 10.1016/j.neuropharm.2020.108158 17655811 1-s2.0-S0028390820302264-main.pdf 1-s2.0-S0028390820302264-main.pdf 1 A2E88438602C7FCE3433CEA477D145EA 911cfb20f906aa40a2cdb4c571b5f4be7831e922187296199b5715acc1775a27 e341c068-f908-11ec-8aca-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=157880 https://www.sciencedirect.com/science/article/pii/S0028390820302264 0 8027df70-f908-11ec-8aca-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=157879 Medicinska fakulteta 0 0 0