Glutamate transport in rat cerebellar granule cells is impaired by inorganic epileptogenic agents

There is evidence that extracellular glutamate levels are elevated in certain brain regions immediately prior to and during induction and propagation of seizures. There appears to be a correlation between the capacity of removing released glutamate and the genesis of epileptiform activity. Some models make use of metals, such as Co²⁺ and Ni²⁺, to induce epilepsy. We used patch-clamp recordings to measure the electrogenic glutamate transport in neuronal cells. The present results indicate that Co²⁺ (1 mM) and Ni²⁺ (5 mM) blocked glutamate transport by 17.6±3.9% (n=5, P<0.05) and by 31.8±6.2% (n=7, P<0.05), respectively. Ni²⁺ inhibited glutamate uptake in a dose-dependent manner. The IC₅₀ value obtained was 66.6 μM and the maximum inhibition was 40%. We conclude that one mechanism that may explain the seizures induced by exposure to those divalent cations is inhibition of the glutamate transporter.