• The Korean Journal of Physiology and Pharmacology
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• v.28 no.5
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• pp.413-422
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• 2024

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 IP₃ 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.

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.2
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• pp.43-49
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• 2008

Flavonoids have been shown to affect calcium signaling in neurons. However, there are no reports on the effect of apigenin on glutamate-induced calcium signaling in neurons. We investigated whether apigenin affects glutamate-induced increase of free intracellular $Ca^{2+}$ concentration ($[Ca^{2+}]_i$) in cultured rat hippocampal neurons, using fura-2-based digital calcium imaging and microfluorimetry. The hippocampal neurons were used between 10 and 13 days in culture from embryonic day 18 rats. Pretreatment of the cells with apigenin ($1{\mu}M$ to $100{\mu}M$) for 5 min inhibited glutamate ($100{\mu}M$, 1 min) induced $[Ca^{2+}]_i$ increase, concentration-dependently. Pretreatment with apigenin ($30{\mu}M$) for 5 min significantly decreased the $[Ca^{2+}]_i$ responses induced by two ionotropic glutamate receptor agonists, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA, $10{\mu}M$, 1 min) and N-methyl-D-aspartate (NMDA, $100{\mu}M$, 1 min), and significantly inhibited the AMPA-induced peak currents. Treatment with apigenin also significantly inhibited the $[Ca^{2+}]_i$ response induced by 50 mM KCl solution, decreased the $[Ca^{2+}]_i$ responses induced by the metabotropic glutamate receptor agonist, (S)-3,5-dihydroxy-phenylglycine (DHPG, 100 $[Ca^{2+}]_i$, 90 s), and inhibited the caffeine (10 mM, 2 min)-induced $[Ca^{2+}]_i$ responses. Furthermore, treatment with apigenin ($30{\mu}M$) significantly inhibited the amplitude and frequency of 0.1 mM $[Mg^{2+}]_o$-induced $[Ca^{2+}]_i$ spikes. These data together suggest that apigenin inhibits glutamate-induced calcium signaling in cultured rat hippocampal neurons.