In:
Journal of Neurochemistry, Wiley, Vol. 79, No. 2 ( 2001-10-15), p. 407-416
Abstract:
The pathways of lead (Pb 2+ ) uptake were studied in fura‐2‐loaded cerebellar granule cells from 8‐day‐old rats. In a nominal Ca‐free external bath, Pb 2+ (5–50 µ m ) determined an increase of the fluorescence emission ratio ( R = E 340 / E 380 ) even in the absence of any specific stimulus. This rise was dose‐dependent, was not significantly affected by m m Mg 2+ or Ca 2+ , but it was readily reversed by the membrane‐permeant heavy metal chelator tetrakis(2‐pyridylmethyl) ethylene‐diamine (TPEN, 100 µ m ), indicating that it was due to Pb 2+ influx. The rate of rise, d R /d t , was increased up to a factor of 5 by depolarizing high‐KCl solution, indicating a sizeable permeation through voltage‐dependent channels. This effect was neither antagonized by nimodipine, nor enhanced by BayK8644, but it was slackened by ω‐agatoxin IVA (200 n m ), suggesting an involvement of non‐L‐type calcium channels. Pb 2+ influx was also stimulated by glutamic acid or NMDA in the presence of 10–30 µ m glycine, but only in Mg‐free solution, suggesting that glutamate channels of the NMDA type are an additional pathway of Pb 2+ uptake. Pb 2+ caused a time‐, dose‐ and stimulus‐dependent saturation of the dye, whose intracellular concentration is ∼ 10 µ m , indicating that intracellular Pb 2+ can readily reach a concentration in the micromolar range. These results indicate that the particular vulnerability of neurones to Pb 2+ poisoning is linked to the presence of specific transport systems, which mediate the rapid uptake of Pb 2+ into the neurone.
Type of Medium:
Online Resource
ISSN:
0022-3042
,
1471-4159
DOI:
10.1046/j.1471-4159.2001.00557.x
Language:
English
Publisher:
Wiley
Publication Date:
2001
detail.hit.zdb_id:
2020528-4
SSG:
12
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