Effect of dantrolene on KCl- or NMDA-induced intracellular Ca2+ changes and spontaneous Ca2+ oscillation in cultured rat frontal cortical neurons

T. Hayashi, A. Kagaya, M. Takebayashi, T. Oyamada, M. Inagaki, Y. Tawara, N. Yokota, J. Horiguchi, T. P. Su, S. Yamawaki

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Abstract

Dantrolene has been known to affect intracellular Ca2+ concentration ([Ca2+](i)) by inhibiting Ca2+ release from intracellular stores in cultured neurons. We were interested in examining this property of dantrolene in influencing the [Ca2+](i) affected by the NMDA receptor ligands, KCl, L-type Ca2+ channel blocker nifedipine, and two other intracellular Ca2+-mobilizing agents caffeine and bradykinin. Effect of dantrolene on the spontaneous oscillation of [Ca2+](i) was also examined. Dantrolene in μM concentrations dose-dependently inhibited the increase in [Ca2+](i) elicited by NMDA and KCl. AP-5, MK-801 (NMDA antagonists), and nifedipine respectively reduced the NMDA and KCl-induced increase in [Ca2+](i). Dantrolene, added to the buffer solution together with the antagonists or nifedipine, caused a further reduction in [Ca2+](i) to a degree similar to that seen with dantrolene alone inhibiting the increase in [Ca2+](i) caused by NMDA or KCl. At 30 μM, dantrolene partially inhibited caffeine-induced increase in [Ca2+](i) whereas it has no effect on the bradykinin-induced change in [Ca2+](i). The spontaneous oscillation of [Ca2+](i) in frontal cortical neurons was reduced both in amplitude and in base line concentration in the presence of 10 μM dantrolene. Our results indicate that dantrolene's mobilizing effects on intracellular Ca2+ stores operate independently from the influxed Ca2+ and that a component of the apparent increase in [Ca2+](i) elicited by NMDA or KCl represents a dantrolene-sensitive Ca2+ release from intracellular stores. Results also suggest that dantrolene does not affect the IP3-gated release of intracellular Ca2+ and that the spontaneous Ca2+ oscillation is, at least partially, under the control of Ca2+ mobilization from internal stores.

Original languageEnglish
Pages (from-to)811-824
Number of pages14
JournalJournal of Neural Transmission
Volume104
Issue number8-9
DOIs
Publication statusPublished - Jan 1 1997

Keywords

  • Ca-induced Ca release
  • Intracellular Ca stores
  • Intracellular free Ca concentration
  • N-methyl-D-aspartate receptor
  • Primary cultures of rat frontal cortical neurons
  • Spontaneous Ca oscillation

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry

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    Hayashi, T., Kagaya, A., Takebayashi, M., Oyamada, T., Inagaki, M., Tawara, Y., Yokota, N., Horiguchi, J., Su, T. P., & Yamawaki, S. (1997). Effect of dantrolene on KCl- or NMDA-induced intracellular Ca2+ changes and spontaneous Ca2+ oscillation in cultured rat frontal cortical neurons. Journal of Neural Transmission, 104(8-9), 811-824. https://doi.org/10.1007/BF01285550