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Ketamine alters functional plasticity of astroglia : an implication for antidepressant effect
ID Stenovec, Matjaž (Author)

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Abstract
Ketamine, a non-competitive N–methyl–D–aspartate receptor (NMDAR) antagonist, exerts a rapid, potent and long-lasting antidepressant effect, although the cellular and molecular mechanisms of this action are yet to be clarified. In addition to targeting neuronal NMDARs fundamental for synaptic transmission, ketamine also affects the function of astrocytes, the key homeostatic cells of the central nervous system that contribute to pathophysiology of major depressive disorder. Here, I review studies revealing that (sub)anesthetic doses of ketamine elevate intracellular cAMP concentration ([cAMP]$_i$) in astrocytes, attenuate stimulus-evoked astrocyte calcium signaling, which regulates exocytotic secretion of gliosignaling molecules, and stabilize the vesicle fusion pore in a narrow configuration, possibly hindering cargo discharge or vesicle recycling. Next, I discuss how ketamine affects astrocyte capacity to control extracellular K$^+$ by reducing vesicular delivery of the inward rectifying potassium channel (K$_{ir}$4.1) to the plasmalemma that reduces the surface density of K$_{ir}$4.1. Modified astroglial K$^+$ buffering impacts upon neuronal firing pattern as demonstrated in lateral habenula in a rat model of depression. Finally, I highlight the discovery that ketamine rapidly redistributes cholesterol in the astrocyte plasmalemma, which may alter the flux of cholesterol to neurons. This structural modification may further modulate a host of processes that synergistically contribute to ketamine’s rapid antidepressant action.

Language:English
Keywords:astrocytes, ketamine, exocytosis, cAMP, endocytosis, fusion pore, K$_{ir}$4.1, vesicle mobility, cholesterol
Work type:Article
Typology:1.02 - Review Article
Organization:MF - Faculty of Medicine
Publication status:Published
Publication version:Version of Record
Year:2021
Number of pages:17 str.
Numbering:Vol. 11, iss. 6, art. 573
PID:20.500.12556/RUL-135741 This link opens in a new window
UDC:616-092
ISSN on article:2075-1729
DOI:10.3390/life11060573 This link opens in a new window
COBISS.SI-ID:67452931 This link opens in a new window
Publication date in RUL:30.03.2022
Views:524
Downloads:104
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Record is a part of a journal

Title:Life
Shortened title:Life
Publisher:MDPI
ISSN:2075-1729
COBISS.SI-ID:519982617 This link opens in a new window

Licences

License:CC BY 4.0, Creative Commons Attribution 4.0 International
Link:http://creativecommons.org/licenses/by/4.0/
Description:This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
Licensing start date:17.06.2021

Secondary language

Language:Slovenian
Keywords:astrociti, ketamin, eksocitoza

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