Yang Ji Seon, Jang Hyun-Jong, Sung Ki-Wug, Rhie Duck-Joo, Yoon Shin Hee
Department of Physiology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
Catholic Neuroscience Institute, The Catholic University of Korea, Seoul 06591, Korea.
Korean J Physiol Pharmacol. 2024 Sep 1;28(5):413-422. doi: 10.4196/kjpp.2024.28.5.413.
Group I metabotropic glutamate receptors (mGluRs) modulate postsynaptic neuronal excitability and epileptogenesis. We investigated roles of group I mGluRs on low extracellular Mg concentration ([Mg])-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 Mg-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 [Mg]-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 Ca-ATPase antagonist, significantly inhibited the spike firing and amplitude of the epileptiform activity. Both the IP 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 [Mg] DMEM-induced neuronal cell death in the CA1 regions, but LY367385 did not. We suggest that mGluR 5 is involved in low [Mg]induced interictal epileptiform activity in the CA1 regions of rat hippocampal slices through PLC, release of Ca from intracellular stores and PKC and TRPC channels, which could be involved in neuronal cell death.
I 型代谢型谷氨酸受体（mGluRs）可调节突触后神经元兴奋性和癫痫发生。我们使用细胞外记录和碘化丙啶染色，研究了 I 型 mGluRs 在无内嗅皮质的离体大鼠海马切片 CA1 区低细胞外镁浓度（[Mg]）诱导的癫痫样活动和神经元细胞死亡中的作用。暴露于无镁人工脑脊液可诱导大鼠海马切片 CA1 区的发作间期癫痫样活动。mGluR 5 拮抗剂 MPEP 显著抑制低[Mg]诱导的癫痫样活动的棘波发放，而 mGluR1 拮抗剂 LY367385 则无此作用。I 型 mGluR 激动剂 DHPG 显著增加癫痫样活动的棘波发放。磷脂酶 C（PLC）抑制剂 U73122 抑制棘波发放。内质网钙-ATP 酶拮抗剂毒胡萝卜素显著抑制癫痫样活动的棘波发放和幅度。肌醇 1,4,5-三磷酸（IP）受体拮抗剂 2-氨基乙氧基二苯硼酸（2-APB）和兰尼碱受体拮抗剂丹曲林均显著抑制棘波发放。蛋白激酶 C（PKC）抑制剂如白屈菜红碱和 GF109203X 显著增加棘波发放。相对特异性的瞬时受体电位通道 C 型 1、4、5（TRPC 1、4、5）通道拮抗剂氟芬那酸显著抑制棘波发放，而相对非特异性的 TRPC 通道拮抗剂 SKF96365 则无此作用。MPEP 显著降低低[Mg]杜氏改良 Eagle 培养基（DMEM）诱导的大鼠海马切片 CA1 区神经元细胞死亡，但 LY367385 则无此作用。我们认为，mGluR 5 通过 PLC、细胞内钙库释放钙以及 PKC 和 TRPC 通道参与大鼠海马切片 CA1 区低[Mg]诱导的发作间期癫痫样活动，这可能与神经元细胞死亡有关。
