Acidosis and 5-(N-ethyl-N-isopropyl)amiloride (EIPA) attenuate zinc/kainate toxicity in cultured cerebellar granule neuronsстатья
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Дата последнего поиска статьи во внешних источниках: 19 сентября 2015 г.
Аннотация:Cultured cerebellar granule neurons (CGNs) were resistant to the toxic effect of ZnCl2 (0.005 mM, 3 h) and slightly sensitive to the effect of kainate (0.1 mM, 3 h). Simultaneous treatment of CGNs with kainate and ZnCl2 caused intensive neuronal death, which was attenuated by external acidosis (pH 6.5) or 5-(N-ethyl-N-isopropyl)amiloride (EIPA, Na+/H+ exchange blocker, 0.03 mM). Intracellular zinc and calcium ion concentrations ([Zn2+]i and [Ca2+]i) were increased under the toxic action of kainate+ZnCl2 thus significantly decreased at the external acidosis and increased at addition of EIPA. Neuronal Zn2+ imaging demonstrated that EIPA increases the cytosolic concentration of free Zn2+ at incubation in the Zn2+ containing solution. These data imply that acidosis reduces ZnCl2/kainate toxic effects by decreasing Zn2+ entry in neurons, and EIPA prevents zinc stores from being overloaded with zinc.