The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Group 1 metabotropic glutamate receptor 5 is involved in synaptically-induced Ca2+-spikes and cell death in cultured rat hippocampal neurons

  • Yang, Ji Seon (Department of Physiology, College of Medicine, The Catholic University of Korea) ;
  • Jeon, Sujeong (Department of Physiology, College of Medicine, The Catholic University of Korea) ;
  • Jang, Hyun-Jong (Department of Physiology, College of Medicine, The Catholic University of Korea) ;
  • Yoon, Shin Hee (Department of Physiology, College of Medicine, The Catholic University of Korea)
  • Received : 2022.07.22
  • Accepted : 2022.10.14
  • Published : 2022.11.01
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Abstract

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 Ca2+ concentration ([Ca2+]i) spikes and neuronal cell death induced by 0.1 mM Mg2+ and 10 µM glycine in cultured rat hippocampal neurons from embryonic day 17 fetal Sprague-Dawley rats using imaging methods for Ca2+ and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays for cell survival. Reduction of extracellular Mg2+ concentration ([Mg2+]o) to 0.1 mM induced repetitive [Ca2+]i spikes within 30 sec at day 11.5. The mGluR5 antagonist 6-Methyl2-(phenylethynyl) pyridine (MPEP) almost completely inhibited the [Ca2+]i spikes, but the mGluR1 antagonist LY367385 did not. The group 1 mGluRs agonist, 3,5-dihydroxyphenylglycine (DHPG), significantly increased the [Ca2+]i spikes. The phospholipase C inhibitor U73122 significantly inhibited the [Ca2+]i spikes in the absence or presence of DHPG. The IP3 receptor antagonist 2-aminoethoxydiphenyl borate or the ryanodine receptor antagonist 8-(diethylamino)octyl 3,4,5-trimethoxybenzoate also significantly inhibited the [Ca2+]i spikes in the absence or presence of DHPG. The TRPC channel inhibitors SKF96365 and flufenamic acid significantly inhibited the [Ca2+]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 [Ca2+]i spikes and neuronal cell death in cultured rat hippocampal neurons by releasing Ca2+ from IP3 and ryanodine-sensitive intracellular stores and activating TRPC channels.

Keywords

Acknowledgement

This work was supported by a grant (NRF-2016R1D1A1B03934176) of the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Republic of Korea.

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