Astrocytes in rapid ketamine antidepressant action

التفاصيل البيبلوغرافية
العنوان: Astrocytes in rapid ketamine antidepressant action
المؤلفون: Robert Zorec, Alexei Verkhratsky, Matjaž Stenovec, Baoman Li
المصدر: Stenovec, M, Li, B, Verkhratsky, A & Zorec, R 2020, ' Astrocytes in rapid ketamine antidepressant action ', Neuropharmacology, vol. 173, pp. 108158 . https://doi.org/10.1016/j.neuropharm.2020.108158Test
Neuropharmacology, vol. 173, 108158, 2020.
سنة النشر: 2020
مصطلحات موضوعية: 0301 basic medicine, Vesicle fusion, ketamine, Psychotomimetic drug, Neurotransmission, Synaptic Transmission, Exocytosis, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, medicine, cytosolic excitability, Animals, Homeostasis, Humans, Calcium Signaling, potassium homeostasis, Calcium signaling, Pharmacology, Depressive Disorder, astroglia, Chemistry, Inward-rectifier potassium ion channel, cholesterol, eksocitoza, Antidepressive Agents, Cell biology, Cholesterol, 030104 developmental biology, medicine.anatomical_structure, ketamin, Astrocytes, udc:616-092, Potassium, Ketamine, exocytosis, 030217 neurology & neurosurgery, Intracellular, Astrocyte
الوصف: 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.
وصف الملف: application/pdf; text/url
اللغة: English
تدمد: 1873-7064
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4865425eb394d856f68a45ceb8f5b8c0Test
https://linkinghub.elsevier.com/retrieve/pii/S0028390820302264Test
حقوق: OPEN
رقم الانضمام: edsair.doi.dedup.....4865425eb394d856f68a45ceb8f5b8c0
قاعدة البيانات: OpenAIRE