Mode of blockade by MK-801 of N-methyl-d-aspartate-induced increase in intracellular Ca2+ in cultured mouse hippocampal neurons

Michisuke Yuzaki, Atsushi Miyawaki, Kyoko Akita, Yoshihisa Kudo, Akihiko Ogura, Hidetoshi Ino, Katsuhiko Mikoshiba

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25 Citations (Scopus)


Microfluorometry with fura-2 was applied to study the action of the anticonvulsant (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) on N-methyl-d-aspartate (NMDA)-induced increase in intracellular Ca2+ concentration ([Ca2+]1) in cultured mouse hippocampal neurons. MK-801 caused a potent and long-lasting blockade of the NMDA-activated [Ca2+]i elevation in a selective manner, not affecting the [Ca2+]i rise induced by quisqualate or kainate. Blockade and recovery from the blockade by MK-801 showed use dependency; the degree of blockade was dependent on the presence of NMDA. The use-dependent onset of antagonism was, however, highly sensitive to the bath temperature. MK-801 applied in the absence of NMDA had no effect on the response to subsequent application of NMDA at 22°C, whereas it reduced the subsequent response to NMDA significantly at 37°C. MK-801 interacted with the receptor-ion channel complex even when Mg2+, which is considered to block the open channel, had already blocked the NMDA-induced [Ca2+]i. The recovery from blockade by MK-801 was not accelerated by the application of 10 mM Mg2+ for 5 min. These results suggest that MK-801 can gain access to its binding site in the absence of NMDA at physiological temperature, and that this binding site is distinct from that for Mg2+.

Original languageEnglish
Pages (from-to)51-56
Number of pages6
JournalBrain Research
Issue number1-2
Publication statusPublished - 1990 May 28
Externally publishedYes


  • Calcium
  • Cell culture
  • Excitatory amino acid receptor
  • Fura-2
  • Hippocampus
  • MK-801
  • Magnesium

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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