Astroglial NMDA receptors inhibit expression of K(ir)4.1 channels in glutamate-overexposed astrocytes in vitro and in the brain of rats with acute liver failure
PBN-AR
Instytucja
Instytut Medycyny Doświadczalnej i Klinicznej im. Mirosława Mossakowskiego Polskiej Akademii Nauk
Informacje podstawowe
Główny język publikacji
en
Czasopismo
NEUROCHEMISTRY INTERNATIONAL
ISSN
0197-0186
EISSN
Wydawca
PERGAMON-ELSEVIER SCIENCE LTD
DOI
URL
Rok publikacji
2015
Numer zeszytu
Strony od-do
20-25
Numer tomu
88
Identyfikator DOI
Liczba arkuszy
1,09
Słowa kluczowe
en
K(ir)4.1
Astrocytic NMDA receptors
Glutamate
Excitotoxicity
Hepatic encephalopathy
Oxidative/nitrosative stress
Streszczenia
Język
en
Treść
Astroglial inward rectifying K(ir)4.1 potassium channels are fundamental for the maintenance of ion and water homeostasis in the central nervous system (CNS). Down-regulation of K(ir)4.1 expression is observed in CNS disorders associated with excessive extracellular glutamate (Glu) accumulation, including hepatic encephalopathy related to acute liver failure CALF). Here we demonstrate that prolonged (3 days) treatment of cultured rat cortical astrocytes with 2 mM Glu or 100 mu M NMDA decreases the expression of K(ir)4.1 mRNA and protein. Inhibition by Glu of K(ir)4.1 mRNA expression was reversed by NMDA receptor antagonists MK-801 and AP-5 (each at 50 mu M), and by a non-transportable inhibitor of Glu uptake TBOA (100 mu M). MK-801 reversed the inhibitory effect of Glu on K(ir)4.1 protein expression. In contrast, transcription of K(ir)4.1 channels was not affected by: (i) a transportable Glu uptake inhibitor PDC (100 mu M); (ii) by group I mGluR antagonist MTEP (100 mu M); (iii) by antagonists of oxidative-nitrosative stress (ONS) in astrocytes, including the neuroprotective amino acid taurine (Tau; 10 mM), the NADPH oxidase inhibitor apocyanine (APO; 300 mu M), the nitric oxide synthase inhibitor, L-NNA (100 mu M), and a membrane permeable glutathione precursor, glutathione-diethyl ester (GEE; 3 mM). Down-regulation of K(ir)4.1 transcription in rats with ALF was attenuated by intraperitoneal administration of a competitive NMDA receptor antagonist memantine, but not by histidine, which reverses ONS associated with ALF. Collectively, the results indicate that over-activation of astroglial NMDA receptors, aided by as yet undefined effects of Glu entry to astrocytes, is a primary cause of the reduction of K(ir)4.1 expression in CNS disorders associated with increased exposure to Glu. (C) 2014 Elsevier Ltd. All rights reserved.
Cechy publikacji
ORIGINAL_ARTICLE
Inne
System-identifier
645337
CrossrefMetadata from Crossref logo
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