Carbachol can potentiate N-methyl-d-aspartate responses in the rat hippocampus by a staurosporine and thapsigargin-insensitive mechanism

Jenni Harvey (Lead / Corresponding author), Richard Balasubramaniam, Graham L. Collingridge

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Experiments were performed to investigate the mechanism underlying the potentiation of N-methyl-d-aspartate (NMDA) responses by carbachol (CCh) in the CA1 region of rat hippocampal slices. CCh (300 nM) potentiated responses to NMDA, but not to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), in a readily reversible manner. Potentiation occurred in slices treated with 200 nM tetrodotoxin and perfused with Mg2+-free medium. It also occurred in slices treated with either staurosporine (1 μM), which is a potent inhibitor of a variety of protein kinases including protein kinase C (PKC), or thapsigargin (10 μM), which depletes intracellular Ca2+ stores by preventing their refilling. However, CCh-induced potentiation was abolished in slices perfused with Ca2+-free medium. These data suggest that low concentrations of CCh can acutely potentiate NMDA responses in the hippocampus by a Ca2+-sensitive process that is probably independent of both the activation of PKC and the release of Ca2+ from intracellular stores. This mechanism is similar to that underlying the potentiation of NMDA responses by the metabotropic glutamate receptor (mGluR) agonist. aminocyclopentane-1S,3R-dicarboxylic acid (1S,3R-ACPD).

Original languageEnglish
Pages (from-to)165-168
Number of pages4
JournalNeuroscience Letters
Volume162
Issue number1-2
DOIs
Publication statusPublished - 12 Nov 1993

Keywords

  • Ca
  • Ca pool
  • Carbachol
  • Hippocampus
  • Long-term potentiation
  • NMDA receptor
  • Protein kinase

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