| Autor: |
Dyatlov, Vladimir A., Platoshin, Alexander V., Lawrence, David A., Carpenter, David O. |
| Zdroj: |
Toxicology and Applied Pharmacology; June 1996, Vol. 138 Issue: 2 p285-297, 13p |
| Abstrakt: |
The effect of HgCl2on kainate (KA)-induced depression of a voltage-gated potassium (K+) current in chick embryo telencephalic cells was studied using conventional and nystatin-perforated whole-cell patch-clamp recordings, fluorescence imaging, and flow cytometry techniques. Hg2+(1 μM) alone did not effect the 4-aminopyridine-(4-AP)-sensitive transient K+current in immature cells (Embryonic Day 5), but irreversibly potentiated the depressant effect of KA on this K+current. A 50% potentiation of KA-induced depression of the K+current was produced by an application of 0.19 μMHg2+. Application of ionomycin (5 μM) or calcium ionophore A23187 (2 μM) suppressed the K+current. To test the possibility that the 4-AP-sensitive transient K+current is a Ca-inactivated current, the effect of intracellular Ca2+concentration ([Ca2+]i) in the range of 30 nMto 2 μMwas determined. The amplitude of the K+current was sensitive to [Ca2+]iwith half-maximal inactivation at 370 nMat +60 mV. The concentration–response curve of the K+current inhibition by [Ca2+]iwas shifted to lower [Ca2+]iand the slope of the curve was reduced in the presence of KA. Hg2+potentiated these effects of KA. The Ca-dependence of the K+current was maximal at the 5th embryonic day, declined to the 9th embryonic day, and was absent at the 11th embryonic day. Application of Hg2+(0.1–1 μM) had no effect on the basal [Ca2+]iof freshly dissociated cells (10th dayin ovo) and cells in culture (the 4-day cultures from the telencephalon of 5-day-old embryos), but potentiated KA-induced increase of [Ca2+]iin a Ca-free-EGTA solution in a concentration-dependent manner. Moreover 1 μMHg2+delayed and reduced the recovery to basal [Ca2+]iafter washout of KA. Exposure to 5–30 μMHg2+caused an irreversible decline of membrane resistance, an increased cell size, and reduced cell granularity and complexity. Intracellular recording of spontaneous neuronal activity and immunocytochemical identification showed that the KA/Hg2+-sensitive Ca-inactivated K+current exists in early differentiating telencephalic neurons. Because depression of the K+current by KA and Hg2+decreases the interspike interval and irreversibly perturbs the frequency code of information in the nervous system, the expression of this current during early neuroembryogenesis may be one of the reasons for the developmental toxicity of inorganic mercury. |
| Databáze: |
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