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Trafficking patterns of NMDA and GABAA receptors in a Mg2+-free cultured hippocampal neuron model of status epilepticus

 Yang-Je Cho  ;  Hyunjeong Kim  ;  Won-Joo Kim  ;  Seungsoo Chung  ;  Young-Hwan Kim  ;  Inja Cho  ;  Byung In Lee  ;  Kyoung Heo 
 Epilepsy Research, Vol.136 : 143-148, 2017 
Journal Title
 Epilepsy Research 
Issue Date
Action Potentials/physiology ; Animals ; Biotinylation ; Cell Membrane/metabolism ; Cell Membrane/pathology ; Cells, Cultured ; Fluorescent Antibody Technique ; Hippocampus/metabolism* ; Hippocampus/pathology ; Magnesium Deficiency ; Neurons/metabolism* ; Neurons/pathology ; Patch-Clamp Techniques ; Protein Transport ; Rats, Sprague-Dawley ; Receptors, GABA-A/metabolism* ; Receptors, N-Methyl-D-Aspartate/metabolism* ; Status Epilepticus/metabolism* ; Status Epilepticus/pathology
Epileptiform activity ; GABA(A) receptor ; Low Mg(2+) solution ; NMDA receptor ; Receptor trafficking ; Status epilepticus
An altered pattern of receptor trafficking is one of the pathophysiologic mechanisms of status epilepticus (SE). The gradual internalization of GABAA receptors (GABARs) occurs in both in vitro and in vivo models of SE and is thought to be a cause of decreased GABAergic inhibition. Unlike GABARs, little is known about alterations in NMDA receptor (NMDAR) trafficking during SE, even though increased activity of NMDARs is indispensable for the induction and maintenance of SE. Therefore, we aimed to simultaneously investigate the changes in the trafficking patterns of GABARs and NMDARs in an in vitro cultured hippocampal neuron model of SE. For induction of epileptiform discharges, hippocampal neurons were exposed to external medium without Mg2+. Biotinylation assay and immunofluorescence staining for GABAR β2,3 and NMDAR NR1 subunits were performed to quantify and visualize surface GABARs and NMDARs, respectively. The frequency of spontaneous action potentials increased more than 4-fold after Mg2+-free induction. The level of surface GABARs decreased over time after Mg2+-free induction, dropping to approximately 50% of control levels an hour after Mg2+-free induction. By contrast, the trafficking of NMDARs to the surface was enhanced after a slight time lag, increasing by 30% of control levels an hour after Mg2+-free induction. Our data showed the changes of both NMDAR and GABAR trafficking during prolonged SE induced by a Mg2+-free extracellular environment and confirmed that this in vitro SE model is suitable for examining alterations in the receptor trafficking pattern by prolonged seizure activity. These results suggest that targeting of surface NMDAR could be a promising method in controlling benzodiazepine-resistant SE.
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1. College of Medicine (의과대학) > Dept. of Physiology (생리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
Yonsei Authors
김영환(Kim, Young Hwan)
김원주(Kim, Won Joo) ORCID logo https://orcid.org/0000-0002-5850-010X
정승수(Chung, Seung Soo) ORCID logo https://orcid.org/0000-0002-3119-9628
조양제(Cho, Yang Je)
허경(Heo, Kyoung)
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