Selective blockade of NMDA-activated channel currents may be implicated in learning deficits caused by lead.
The effect of Pb2+ on glutamate receptor activity in rat hippocampal neurons was investigated with a view of explaining the cognitive and learning deficits produced by this heavy metal. Pb2+ (2.5-50 microM) selectively inhibited N-methyl-D-aspartate (NMDA)-induced whole-cell and single-channel currents in a concentration-dependent but voltage-independent manner, without significantly altering currents induced by either quisqualate or kainate. The frequency of NMDA-induced channel activation was decreased by Pb2+. Neither glycine (10-100 microM), nor Ca2+ (10 mM) reversed the effect of Pb2+. Pb2+ also inhibited the [3H]MK-801 binding to rat hippocampal membranes in vitro. The elucidation of the actions of Pb2+ on the NMDA receptor ion channel complex provides important insights into the clinical and toxic effects of this cation.
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore 21201.
M
M
Alkondon
A C
AC
Costa
V
V
Radhakrishnan
R S
RS
Aronstam
E X
EX
Albuquerque
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D003986:Dibenzocycloheptenes / Q000378:metabolism; D016291:Dizocilpine Maleate; D004553:Electric Conductivity; D005998:Glycine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007473:Ion Channels / Q000187:drug effects* / Q000502:physiology; D007608:Kainic Acid / Q000494:pharmacology; D007854:Lead / Q000494:pharmacology* / Q000633:toxicity; D007859:Learning Disabilities / Q000139:chemically induced*; D008297:Male; D016202:N-Methylaspartate; D010069:Oxadiazoles / Q000494:pharmacology; D016318:Quisqualic Acid; D051381:Rats; D011919:Rats, Inbred Strains; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology
D003986:Dibenzocycloheptenes; D007473:Ion Channels; D010069:Oxadiazoles; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D007854:Lead; D001224:Aspartic Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D016318:Quisqualic Acid; D007608:Kainic Acid; D002118:Calcium; D005998:Glycine