Kynurenic acid blocks nicotinic synaptic transmission to hippocampal interneurons in young rats

Eur J Neurosci. 2007 May;25(9):2656-65. doi: 10.1111/j.1460-9568.2007.05540.x. Epub 2007 Apr 25.


The tryptophan metabolite kynurenic acid can block glutamate at ionotropic receptors, but recent evidence suggests a more potent antagonistic action at alpha7 nicotinic receptors for acetylcholine on cultured neurons. The present study examines activity of kynurenic acid at those nicotinic receptors, which mediate cholinergic neurotransmission onto interneurons in the rat hippocampus. Intracellular recordings were made from pyramidal cells and interneurons in the presence of atropine, bicuculline methobromide, (3-aminopropyl)(diethoxymethyl)-phosphinic acid [CGP35348, to block gamma-aminobutyric acid (GABA)(B) receptors] and 3-tropanyl-3,5-dichlorobenzoate (MDL 72222, to block 5-HT3 receptors). In the added presence of glutamate antagonists 2-amino-5-phosphono-pentanoic acid and 6-cyano-7-nitroquinoxaline-2,3-dione, interneurons exhibited a residual excitatory postsynaptic potential (EPSP) that could be blocked by the nicotinic alpha7 receptor blocker methyl-lycaconitine, but not by dihydro-beta-erythroidine which blocks alpha4beta2 receptors. Kynurenic acid reduced the amplitude of these EPSPs with an EC50 of 136 microM. The amplitudes of nicotinic spontaneous miniature EPSPs were also reduced by methyl-lycaconitine and kynurenic acid. The results show that kynurenic acid is more potent in blocking nicotinic EPSPs compared with the full, glutamate-mediated EPSPs, but it was substantially less potent than has been reported in cultures, possibly because of differences in the accessibility of synaptic and extrasynaptic receptors. It is suggested that blockade of nicotinic synaptic transmission may be relevant to the actions of kynurenic acid in the hippocampus, but that in the intact brain this activity is likely to be comparable in importance to the blockade of glutamate-mediated transmission.

MeSH terms

  • Acetylcholine / metabolism
  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Aging / physiology
  • Animals
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • GABA Antagonists / pharmacology
  • Hippocampus / cytology
  • Hippocampus / growth & development*
  • Hippocampus / metabolism*
  • Interneurons / cytology
  • Interneurons / drug effects
  • Interneurons / metabolism*
  • Kynurenic Acid / pharmacology*
  • Male
  • Neural Pathways / drug effects
  • Neural Pathways / metabolism
  • Nicotinic Antagonists / pharmacology
  • Organ Culture Techniques
  • Pyramidal Cells / cytology
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Nicotinic / drug effects
  • Receptors, Nicotinic / metabolism*
  • Serotonin Antagonists / pharmacology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*


  • Excitatory Amino Acid Antagonists
  • GABA Antagonists
  • Nicotinic Antagonists
  • Receptors, Nicotinic
  • Serotonin Antagonists
  • Kynurenic Acid
  • Acetylcholine