Roles of metabotropic glutamate receptor 5 in low Mg2+ o -inducedinterictal epileptiform activity in rat hippocampal slices
10.4196/kjpp.2024.28.5.413
- Author:
Ji Seon YANG
1
;
Hyun-Jong JANG
;
Ki-Wug SUNG
;
Duck-Joo RHIE
;
Shin Hee YOON
Author Information
1. Department of Physiology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
- Publication Type:Original Article
- From:The Korean Journal of Physiology and Pharmacology
2024;28(5):413-422
- CountryRepublic of Korea
- Language:English
-
Abstract:
Group I metabotropic glutamate receptors (mGluRs) modulate postsynaptic neuronal excitability and epileptogenesis. We investigated roles of group I mGluRs on low extracellular Mg2+ concentration ([Mg2+ ]o )-induced epileptiform activity and neuronal cell death in the CA1 regions of isolated rat hippocampal slices without the entorhinal cortex using extracellular recording and propidium iodide staining. Exposure to Mg2+ -free artificial cerebrospinal fluid can induce interictal epileptiform activity in the CA1 regions of rat hippocampal slices. MPEP, a mGluR 5 antagonist, significantly inhibited the spike firing of the low [Mg2+ ]o -induced epileptiform activity, whereas LY367385, a mGluR1 antagonist, did not. DHPG, a group 1 mGluR agonist, significantly increased the spike firing of the epileptiform activity.U73122, a PLC inhibitor, inhibited the spike firing. Thapsigargin, an ER Ca2+ -ATPase antagonist, significantly inhibited the spike firing and amplitude of the epileptiform activity. Both the IP 3 receptor antagonist 2-APB and the ryanodine receptor antagonist dantrolene significantly inhibited the spike firing. The PKC inhibitors such as chelerythrine and GF109203X, significantly increased the spike firing. Flufenamic acid, a relatively specific TRPC 1, 4, 5 channel antagonist, significantly inhibited the spike firing, whereas SKF96365, a relatively non-specific TRPC channel antagonist, did not.MPEP significantly decreased low [Mg2+ ] o DMEM-induced neuronal cell death in the CA1 regions, but LY367385 did not. We suggest that mGluR 5 is involved in low [Mg2+ ]o -induced interictal epileptiform activity in the CA1 regions of rat hippocampal slices through PLC, release of Ca2+ from intracellular stores and PKC and TRPC channels, which could be involved in neuronal cell death.
