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Mok MH, Fricker AC, Weil A, Kew JN: Electrophysiological characterisation of the actions of kynurenic acid at ligand-gated ion channels. Neuropharmacology. 2009 Sep;57(3):242-9. Epub 2009 Jun 11.
To better understand the effects of the tryptophan metabolite kynurenic acid (kynA) in the brain, we characterised its actions at five ligand-gated ion channels: NMDA, AMPA, GABA (A), glycine and alpha7 nicotinic acetylcholine receptors. Using whole-cell patch-clamp recordings, we found that kynA was a more potent antagonist at human NR1a/NR2A compared with NR1a/NR2B receptors (IC (50): 158 muM and 681 muM, respectively; in 30 muM glycine). KynA inhibited AMPA-evoked currents to a similar degree in cultured hippocampal neurons and a human GluR2 (flip/unedited) cell line (IC (50): 433 and 596 muM, respectively) and at higher concentrations, kynA also inhibited the strychnine-sensitive glycine receptor ( approximately 35% inhibition by 3 mM kynA). Interestingly, kynA inhibited the peak amplitude (IC (50): 2.9 mM for 10 muM GABA) and slowed the decay kinetics of GABA-evoked currents in cultured neurons. In contrast, we found that kynA (1-3 mM) had no effect on ACh-evoked, methyllycaconitine (MLA)-sensitive currents in a human alpha7 nicotinic receptor (nAChR) cell line, rat hippocampal neurons in primary culture or CA1 stratum radiatum interneurons in rat brain slices. However, DMSO (> 1%) did inhibit alpha7 nAChR-mediated currents. In conclusion, kynA is an antagonist at NMDA, AMPA and glycine receptors and a modulator of GABA (A) receptors, but we find no evidence for any effect of kynA at the alpha7 nAChR. |
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