- 1The effects of neomycin on NMDA-evoked currents in isolated CA1 hippocampal pyramidal neurones were investigated and single channel activity was examined in outside-out patches taken from cultured hippocampal neurones. The effects of neomycin on two combinations of NMDA receptor subunits (NR1a-NR2A and NR1a-NR2B) expressed in human embryonic kidney (HEK293) cells were also studied.
- 2Neomycin (0.01–1 mm) caused a potentiation of NMDA-activated currents in all neurones examined. No evidence of a voltage-dependent depression was observed in whole-cell recordings.
- 3In outside-out patch recordings relatively low concentrations (30 and 100 μm) of neomycin caused a voltage-dependent reduction in single channel current amplitude as well as a large increase in the frequency of channel opening.
- 4In saturating concentrations of glycine, neomycin enhanced NMDA-activated currents and this glycine-independent enhancement was confirmed using recombinant NR1a-NR2B receptors. Neomycin substantially increased the potency of glycine for the receptor by reducing the rate of dissociation of glycine from the receptor. Neomycin demonstrated a glycine-dependent enhancement of currents mediated by the NR1a-NR2A combination of subunits but a paradoxical depression was observed in saturating concentrations of glycine.
- 5Neomycin increased the rate of deactivation of glutamate-activated currents consistent with neomycin causing a reduction in the affinity of the receptor for agonist.
- 6These results indicate that neomycin has multiple and complex effects on NMDA receptors.