Stimulation of kainate toxicity by zinc in cultured cerebellar granule neurons and the role of mitochondria in this process

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.

► Kainate, zinc and calcium ions as synergists in neuronal toxicity.
► Kainate potentiates zinc toxicity in neurons.
► Mitochondria are involved in zinc toxicity.
► Zinc ions toxicity is exerted after transport in mitochondria.