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Stimulation of kainate toxicity by zinc in cultured cerebellar granule neurons and the role of mitochondria in this process |
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| Authors: | Lozier Ekaterina R Stelmashook Elena V Uzbekov Rustem E Novikova Svetlana V Zorov Savva D Alieva Irina B Arbeille Brigitte Zorov Dmitry B Isaev Nickolay K |
| Affiliation: | a A. N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, 119992 Moscow, Russia b Institute of Neurology, Department of Brain Research, Russian Academy of Medical Sciences, per. Obukha 5, 105064 Moscow, Russia c Faculty of Bioengineering and Bioinformatics, Moscow State University, 119992 Moscow, Russia d Laboratory of Cell Biology and Electron Microscopy, Faculty of Medicine, University Francois Rabelais, 10, Boulevard Tonnelle, 37032 Tours, France |
| Abstract: | Zinc chloride (0.01 mM kept for 3 h) is not toxic to cultured cerebellar granule neurons (CGNs) while kainate (0.1 mM kept for 3 h) demonstrates some but very low toxicity towards these cells.Measurements of the relative intraneuronal zinc ion concentration showed that increase in [Zn2+]i under the simultaneous action of ZnCl2 and kainate was significantly stronger compared to their separate action. Simultaneous treatment of CGNs with kainate and zinc chloride caused the swelling of neuronal mitochondria and consequent intensive neuronal death, which was totally prevented by NBQX (an AMPA/kainate-receptors blocker) or ruthenium red (a mitochondrial Ca2+ uniporter blocker). These data imply that Zn2+ synergistically to kainate increase their separate toxic effects on mitochondria leading to rapid neuronal death. |
| Keywords: | Zinc Calcium Kainate Mitochondria Ruthenium red |
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