Alkondon M, Costa A C, Radhakrishnan V, Aronstam R S, Albuquerque E X
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore 21201.
FEBS Lett. 1990 Feb 12;261(1):124-30. doi: 10.1016/0014-5793(90)80652-y.
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.
为了解释这种重金属所导致的认知和学习缺陷，研究了Pb2+对大鼠海马神经元中谷氨酸受体活性的影响。Pb2+（2.5 - 50微摩尔）以浓度依赖性但电压非依赖性的方式选择性抑制N - 甲基 - D - 天冬氨酸（NMDA）诱导的全细胞电流和单通道电流，而对quisqualate或kainate诱导的电流没有显著影响。Pb2+降低了NMDA诱导的通道激活频率。甘氨酸（10 - 100微摩尔）和Ca2+（10毫摩尔）均不能逆转Pb2+的作用。Pb2+在体外也抑制[3H]MK - 801与大鼠海马膜的结合。阐明Pb2+对NMDA受体离子通道复合物的作用，为深入了解该阳离子的临床和毒性作用提供了重要见解。
