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

研究成果: Article査読

26 被引用数 (Scopus)

抄録

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+.

本文言語English
ページ(範囲)51-56
ページ数6
ジャーナルBrain Research
517
1-2
DOI
出版ステータスPublished - 1990 5月 28
外部発表はい

ASJC Scopus subject areas

  • 神経科学(全般)
  • 分子生物学
  • 臨床神経学
  • 発生生物学

フィンガープリント

「Mode of blockade by MK-801 of N-methyl-d-aspartate-induced increase in intracellular Ca2+ in cultured mouse hippocampal neurons」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル