Selective blockade of NMDA‐activated channel currents may be implicated in learning deficits caused by lead

FEBS Letters

Radhakrishnan, Veeraswamy¹  Aronstam, Robert S.²  Costa, Alberto C.S.¹  Alkondon, Manickavasagom¹  Albuquerque, Edson X.¹ 

[1] Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, MD 21201, USA;Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, GA 30912, USA

关键词: Glutamate receptor;    Rat hippocampal neuron;    Lead poisoning;    Single channel current;    Heavy metal;    Learning deficit;    NMDA;    N-methyl-D-aspartate;    LTP;    long-term potentiation;    Hepes;    4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid;   

DOI  :  10.1016/0014-5793(90)80652-Y

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 μ;M) 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 μ;M), 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.

【 授权许可】

Unknown