A role for intracellular zinc in glioma alteration of neuronal chloride equilibrium

摘要: Glioma patients commonly suffer from epileptic seizures. However, the mechanisms of glioma-associated epilepsy are far to be completely understood. Using glioma-neurons co-cultures, we found that tumor cells able deeply influence neuronal chloride homeostasis, by depolarizing reversal potential γ-aminobutyric acid (GABA)-evoked currents (EGABA). EGABA shift is due zinc-dependent reduction KCC2 activity and requires glutamate release glioma cells. Consistently, intracellular zinc loading rapidly depolarizes in mouse hippocampal neurons, through Src/Trk pathway this effect promptly reverted upon chelation. This study provides a possible molecular mechanism linking invasion excitation/inhibition imbalance seizures, zinc–mediated disruption homeostasis.