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

There is evidence that extracellular glutamate levels are elevated in certa in brain regions immediately prior to and during induction and propagation of seizures. There appears to be a correlation between the capacity of remo ving released glutamate and the genesis of epileptiform activity. Some mode ls make use of metals, such as Co2+ and Ni2+, to induce epilepsy. We used p atch-clamp recordings to measure the electrogenic glutamate transport in ne uronal 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 muM and the ma ximum inhibition was 40%. We conclude that one mechanism that may explain t he seizures induced by exposure to those divalent cations is inhibition of the glutamate transporter. (C) 2001 Elsevier Science Ireland Ltd. All right s reserved.