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Group 1 metabotropic glutamate receptor 5 is involved in synaptically-induced Ca(2+)-spikes and cell death in cultured rat hippocampal neurons
Group 1 metabotropic glutamate receptors (mGluRs) can positively affect postsynaptic neuronal excitability and epileptogenesis. The objective of the present study was to determine whether group 1 mGluRs might be involved in synaptically-induced intracellular free Ca(2+) concentration ([Ca(2+)](i)) s...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Korean Physiological Society and The Korean Society of Pharmacology
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9614404/ https://www.ncbi.nlm.nih.gov/pubmed/36302627 http://dx.doi.org/10.4196/kjpp.2022.26.6.531 |
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author | Yang, Ji Seon Jeon, Sujeong Jang, Hyun-Jong Yoon, Shin Hee |
author_facet | Yang, Ji Seon Jeon, Sujeong Jang, Hyun-Jong Yoon, Shin Hee |
author_sort | Yang, Ji Seon |
collection | PubMed |
description | Group 1 metabotropic glutamate receptors (mGluRs) can positively affect postsynaptic neuronal excitability and epileptogenesis. The objective of the present study was to determine whether group 1 mGluRs might be involved in synaptically-induced intracellular free Ca(2+) concentration ([Ca(2+)](i)) spikes and neuronal cell death induced by 0.1 mM Mg(2+) and 10 µM glycine in cultured rat hippocampal neurons from embryonic day 17 fetal Sprague–Dawley rats using imaging methods for Ca(2+) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays for cell survival. Reduction of extracellular Mg(2+) concentration ([Mg(2+)](o)) to 0.1 mM induced repetitive [Ca(2+)](i) spikes within 30 sec at day 11.5. The mGluR5 antagonist 6-Methyl-2-(phenylethynyl) pyridine (MPEP) almost completely inhibited the [Ca(2+)](i) spikes, but the mGluR1 antagonist LY367385 did not. The group 1 mGluRs agonist, 3,5-dihydroxyphenylglycine (DHPG), significantly increased the [Ca(2+)](i) spikes. The phospholipase C inhibitor U73122 significantly inhibited the [Ca(2+)](i) spikes in the absence or presence of DHPG. The IP(3) receptor antagonist 2-aminoethoxydiphenyl borate or the ryanodine receptor antagonist 8-(diethylamino)octyl 3,4,5-trimethoxybenzoate also significantly inhibited the [Ca(2+)](i) spikes in the absence or presence of DHPG. The TRPC channel inhibitors SKF96365 and flufenamic acid significantly inhibited the [Ca(2+)](i) spikes in the absence or presence of DHPG. The mGluR5 antagonist MPEP significantly increased the neuronal cell survival, but mGluR1 antagonist LY367385 did not. These results suggest a possibility that mGluR5 is involved in synaptically-induced [Ca(2+)](i) spikes and neuronal cell death in cultured rat hippocampal neurons by releasing Ca(2+) from IP(3) and ryanodine-sensitive intracellular stores and activating TRPC channels. |
format | Online Article Text |
id | pubmed-9614404 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | The Korean Physiological Society and The Korean Society of Pharmacology |
record_format | MEDLINE/PubMed |
spelling | pubmed-96144042022-11-04 Group 1 metabotropic glutamate receptor 5 is involved in synaptically-induced Ca(2+)-spikes and cell death in cultured rat hippocampal neurons Yang, Ji Seon Jeon, Sujeong Jang, Hyun-Jong Yoon, Shin Hee Korean J Physiol Pharmacol Original Article Group 1 metabotropic glutamate receptors (mGluRs) can positively affect postsynaptic neuronal excitability and epileptogenesis. The objective of the present study was to determine whether group 1 mGluRs might be involved in synaptically-induced intracellular free Ca(2+) concentration ([Ca(2+)](i)) spikes and neuronal cell death induced by 0.1 mM Mg(2+) and 10 µM glycine in cultured rat hippocampal neurons from embryonic day 17 fetal Sprague–Dawley rats using imaging methods for Ca(2+) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays for cell survival. Reduction of extracellular Mg(2+) concentration ([Mg(2+)](o)) to 0.1 mM induced repetitive [Ca(2+)](i) spikes within 30 sec at day 11.5. The mGluR5 antagonist 6-Methyl-2-(phenylethynyl) pyridine (MPEP) almost completely inhibited the [Ca(2+)](i) spikes, but the mGluR1 antagonist LY367385 did not. The group 1 mGluRs agonist, 3,5-dihydroxyphenylglycine (DHPG), significantly increased the [Ca(2+)](i) spikes. The phospholipase C inhibitor U73122 significantly inhibited the [Ca(2+)](i) spikes in the absence or presence of DHPG. The IP(3) receptor antagonist 2-aminoethoxydiphenyl borate or the ryanodine receptor antagonist 8-(diethylamino)octyl 3,4,5-trimethoxybenzoate also significantly inhibited the [Ca(2+)](i) spikes in the absence or presence of DHPG. The TRPC channel inhibitors SKF96365 and flufenamic acid significantly inhibited the [Ca(2+)](i) spikes in the absence or presence of DHPG. The mGluR5 antagonist MPEP significantly increased the neuronal cell survival, but mGluR1 antagonist LY367385 did not. These results suggest a possibility that mGluR5 is involved in synaptically-induced [Ca(2+)](i) spikes and neuronal cell death in cultured rat hippocampal neurons by releasing Ca(2+) from IP(3) and ryanodine-sensitive intracellular stores and activating TRPC channels. The Korean Physiological Society and The Korean Society of Pharmacology 2022-11-01 2022-11-01 /pmc/articles/PMC9614404/ /pubmed/36302627 http://dx.doi.org/10.4196/kjpp.2022.26.6.531 Text en Copyright © Korean J Physiol Pharmacol https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0 (https://creativecommons.org/licenses/by-nc/4.0/) ) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Yang, Ji Seon Jeon, Sujeong Jang, Hyun-Jong Yoon, Shin Hee Group 1 metabotropic glutamate receptor 5 is involved in synaptically-induced Ca(2+)-spikes and cell death in cultured rat hippocampal neurons |
title | Group 1 metabotropic glutamate receptor 5 is involved in synaptically-induced Ca(2+)-spikes and cell death in cultured rat hippocampal neurons |
title_full | Group 1 metabotropic glutamate receptor 5 is involved in synaptically-induced Ca(2+)-spikes and cell death in cultured rat hippocampal neurons |
title_fullStr | Group 1 metabotropic glutamate receptor 5 is involved in synaptically-induced Ca(2+)-spikes and cell death in cultured rat hippocampal neurons |
title_full_unstemmed | Group 1 metabotropic glutamate receptor 5 is involved in synaptically-induced Ca(2+)-spikes and cell death in cultured rat hippocampal neurons |
title_short | Group 1 metabotropic glutamate receptor 5 is involved in synaptically-induced Ca(2+)-spikes and cell death in cultured rat hippocampal neurons |
title_sort | group 1 metabotropic glutamate receptor 5 is involved in synaptically-induced ca(2+)-spikes and cell death in cultured rat hippocampal neurons |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9614404/ https://www.ncbi.nlm.nih.gov/pubmed/36302627 http://dx.doi.org/10.4196/kjpp.2022.26.6.531 |
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