Summary
The actions of Pb2+ on NMDA channel currents of acutely dissociated hippocampal CA1- and CA3-neurones from adult rats activated by aspartate plus glycine (asp/gly) were examined. A fast reversible and a slow irreversible response to Pb2+ were found. Pb2+ applied simultaneously with asp/gly decreased an inward current. The threshold concentration was below 2 μM, the current was reduced > 90% at concentrations over 100 μM, The decrease of the asp/gly activated current showed no voltage dependence. Opening of NMDA channels was not necessary for Pb2+-action, as preincubation in 50 μM Pb2+-containing external solution for several seconds dramatically reduced the response to asp/gly/Pb2+. This effect was reversed within 2 to 5 s of wash. Presence of Pb2+ or asp/Pb2+ or glycine/Pb2+ in the external solution did not prevent recovery of the NMDA receptor/channel complex from desensitization. Prolonged perfusion of a cell with the asp/gly/Pb2+-containing external solution resulted in an irreversible decrease of the asp/gly current, whereas the amplitude of the asp/gly/Pb2+ response did not change over the duration of an experiment. We conclude that Pb2+ modulates NMDA channel activity via interaction with the NMDA/glycine receptor: as a result the channel current decreases.
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Abbreviations
- NMDA:
-
N-methyl-D-aspartate
- LTP:
-
long-term potentiation
- AP5:
-
2-amino-5-phosphonovalerate
- EGTA:
-
ethylene glycol bis(-aminoethylether)-N,N,N′,N′-tetraacetic acid
- HEPES:
-
4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid
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Correspondence to H. L. Haas at the above address
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Uteshev, V., Büsselberg, D. & Haas, H.L. Pb2+ modulates the NMDA-receptor-channel complex. Naunyn-Schmiedeberg's Arch Pharmacol 347, 209–213 (1993). https://doi.org/10.1007/BF00169269
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DOI: https://doi.org/10.1007/BF00169269