Kynurenic acid blocks nicotinic synaptic transmission to hippocampal interneurons in young rats
- 1 May 2007
- journal article
- Published by Wiley in European Journal of Neuroscience
- Vol. 25 (9), 2656-2665
- https://doi.org/10.1111/j.1460-9568.2007.05540.x
Abstract
The tryptophan metabolite kynurenic acid can block glutamate at ionotropic receptors, but recent evidence suggests a more potent antagonistic action at α7 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 γ-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 α7 receptor blocker methyl-lycaconitine, but not by dihydro-β-erythroidine which blocks α4β2 receptors. Kynurenic acid reduced the amplitude of these EPSPs with an EC50 of 136 µm. 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.Keywords
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