Pb2+ modulates the NMDA-receptor-channel complex |
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Authors: | Vladimir Uteshev Dietrich Büsselberg Helmut L. Haas |
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Affiliation: | (1) Institut für Physiologic II, Heinrich-Heine Universität, Moorenstrasse 5, W-4000 Düsseldorf 1, Federal Republic of Germany |
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Abstract: | 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 M, the current was reduced > 90% at concentrations over 100 M, 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 M 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.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 acidCorrespondence to H. L. Haas at the above address |
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Keywords: | Hippocampal neurones NMDA receptor/channel complex Pb2+ NMDA channel blockade |
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