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Multiple sites of action of neomycin, Mg 2+ and spermine on the NMDA receptors of rat hippocampal CA1 pyramidal neurones
Author(s) -
Lu WeiYang,
Xiong ZhiGang,
Orser Beverley A.,
MacDonald John F.
Publication year - 1998
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1998.029bf.x
Subject(s) - neomycin , nmda receptor , glutamate receptor , hippocampal formation , receptor , glycine , agonist , chemistry , biophysics , pharmacology , biology , biochemistry , endocrinology , amino acid , antibiotics
1 The 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. 2 Neomycin (0.01–1 m m ) caused a potentiation of NMDA‐activated currents in all neurones examined. No evidence of a voltage‐dependent depression was observed in whole‐cell recordings. 3 In outside‐out patch recordings relatively low concentrations (30 and 100 μ m ) of neomycin caused a voltage‐dependent reduction in single channel current amplitude as well as a large increase in the frequency of channel opening. 4 In 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. 5 Neomycin increased the rate of deactivation of glutamate‐activated currents consistent with neomycin causing a reduction in the affinity of the receptor for agonist. 6 These results indicate that neomycin has multiple and complex effects on NMDA receptors.