Effects of Apigenin on Glutamate-induced $[Ca^{2+}]_i$ Increases in Cultured Rat Hippocampal Neurons

  • Han, Ji-Hwa (Departments of Physiology, College of Medicine, The Catholic University of Korea) ;
  • Kim, Ki-Jung (Departments of Pharmacology, College of Medicine, The Catholic University of Korea) ;
  • Jang, Hyun-Jong (Departments of Physiology, College of Medicine, The Catholic University of Korea) ;
  • Jang, Ju-Ho (Departments of Physiology, College of Medicine, The Catholic University of Korea) ;
  • Kim, Myung-Jun (Departments of Physiology, College of Medicine, The Catholic University of Korea) ;
  • Sung, Ki-Wug (Departments of Pharmacology, College of Medicine, The Catholic University of Korea) ;
  • Rhie, Duck-Joo (Departments of Physiology, College of Medicine, The Catholic University of Korea) ;
  • Jo, Yang-Hyeok (Departments of Physiology, College of Medicine, The Catholic University of Korea) ;
  • Hahn, Sang-June (Departments of Physiology, College of Medicine, The Catholic University of Korea) ;
  • Lee, Mun-Yong (Departments of Pharmacology, College of Medicine, The Catholic University of Korea) ;
  • Yoon, Shin-Hee (Departments of Physiology, College of Medicine, The Catholic University of Korea)
  • 발행 : 2008.04.30

초록

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.

키워드

참고문헌

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