Pathways of cadmium influx in mammalian neurons

被引:54
作者
Usai, C [1 ]
Barberis, A [1 ]
Moccagatta, L [1 ]
Marchetti, C [1 ]
机构
[1] CNR, Ist Cibernet & Biofis, I-16149 Genoa, Italy
关键词
cadmium uptake; calcium channel; glutamate receptors; neurotoxicity; fura; 2;
D O I
10.1046/j.1471-4159.1999.0722154.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The influx of the toxic cation Cd2+ was studied in fura 2-loaded rat cerebellar granule neurons. in cells depolarized with Ca2+-free, high-KCl solutions, the fluorescence emission ratio (R) increased in the presence of 100 mu M Cd2+. This increase was fully reversed by the Cd2+ chelator tetrakis(2-pyridylmethyl)ethylenediamine indicating a cadmium influx into the cell. The rate of increase, dR/dt, was greatly reduced (67 +/- 5%) by 1 mu M nimodipine and enhanced by 1 mu M Bay K 8644, Concurrent application of nimodipine and omega-agatoxin IVA (200 nM) blocked Cd2+ permeation almost completely (88 +/- 5%), whereas omega-conotoxin MVIIC (2 mu M) reduced dR/dt by 24 +/- 8%, These results indicate a primary role of voltage-dependent calcium channels in Cd2+ permeation. Stimulation with glutamate or NMDA and glycine also caused a rise of R in external Cd2+. Simultaneous application of nimodipine and omega-agatoxin IVA moderately reduced dR/dt (25 +/- 3%). NMDA-driven Cd2+ entry was almost completely prevented by 1 mM Mg2+, 50 mu M memantine, and 10 mu M 5,7-dichlorokynurenic acid, suggesting a major contribution of NMDA-gated channels in glutamate-stimulated Cd2+ influx. Moreover, perfusion with alpha-amino 3-hydroxy-5-methylisoxazole-4-propionate caused a slow increase of R. These results suggest that Cd2+ permeates the cell membrane mainly through the same pathways of Ca2+ influx.
引用
收藏
页码:2154 / 2161
页数:8
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