Voltage-dependent inhibition of recombinant NMDA receptor-mediated currents by 5-hydroxytryptamine



Publication Details

Kloda, A. & Adams, D. J. (2005). Voltage-dependent inhibition of recombinant NMDA receptor-mediated currents by 5-hydroxytryptamine. British Journal of Pharmacology, 144 (3), 323-330.


1 The effect of 5-HT and related indolealkylamines on heteromeric recombinant NMDA receptors expressed in Xenopus oocytes was investigated using the two-electrode voltage-clamp recording technique.

2 In the absence of external Mg 2+ ions, 5-HT inhibited NMDA receptor-mediated currents in a concentration-dependent manner. The inhibitory effect of 5-HT was independent of the NR1a and NR2 subunit combination.

3 The inhibition of glutamate-evoked currents by 5-HT was use- and voltage-dependent. The voltage sensitivity of inhibition for NR1a+NR2 subunit combinations by 5-HT was similar, exhibiting an e-fold change per ∼20 mV, indicating that 5-HT binds to a site deep within the membrane electric field.

4 The inhibition of the open NMDA receptor by external Mg 2+ and 5-HT was not additive, suggesting competition between Mg 2+ and 5-HT for a binding site in the NMDA receptor channel. The concentration-dependence curves for 5-HT and 5-methoxytryptamine (5-MeOT) inhibition of NMDA receptor-mediated currents are shifted to the right in the presence of external Mg 2+.

5 The related indolealkylamines inhibited glutamate-evoked currents with the following order of inhibitory potency: 5-MeOT = 5-methyltryptamine > tryptamine > 7-methyltryptamine > 5-HT ≫ tryptophan = melatonin.

6 Taken together, these data suggest that 5-HT and related compounds can attenuate glutamate-mediated excitatory synaptic responses and may provide a basis for drug treatment of excitoxic neurodegeneration.

Please refer to publisher version or contact your library.



Link to publisher version (DOI)