Premium
Pathways of Cadmium Influx in Mammalian Neurons
Author(s) -
Usai Cesare,
Barberis Andrea,
Moccagatta Luca,
Marchetti Carla
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0722154.x
Subject(s) - chemistry , nmda receptor , glutamate receptor , biophysics , nimodipine , calcium , biochemistry , biology , receptor , organic chemistry
The Influx of the toxic cation Cd 2+ was studied in fura 2‐loaded rat cerebellar granule neurons. In cells depolarized with Ca 2+ ‐free, high‐KCI solutions, the fluorescence emission ratio ( R ) increased in the presence of 100 γ M Cd 2+ . This increase was fully reversed by the Cd 2+ 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 γ M nimodipine and enhanced by 1 γ M Bay K 8644. Concurrent application of nimodipine and ω‐agatoxin IVA (200 n M ) blocked Cd 2+ permeation almost completely (88 ± 5%), whereas ω‐conotoxin MVIIC (2 γ M ) reduced dR/dt by 24 ± 8%. These results indicate a primary role of voltage‐dependent calcium channels in Cd 2+ permeation. Stimulation with glutamate or NMDA and glycine also caused a rise of R in external Cd 2+ . Simultaneous application of nimodipine and ω‐agatoxin IVA moderately reduced dR/dt (25 ± 3%). NMDA‐driven Cd 2+ entry was almost completely prevented by 1 m M Mg 2+ , 50 γ M memantine, and 10 γ M 5,7‐dichlorokynurenic acid, suggesting a major contribution of NMDA‐gated channels in glutamate‐stimulated Cd 2+ influx. Moreover, perfusion with α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate caused a slow increase of R . These results suggest that Cd 2+ permeates the cell membrane mainly through the same pathways of Ca 2+ influx.